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Sample records for adjuvant platinum-based chemotherapy

  1. Adjuvant platinum-based chemotherapy for early stage cervical cancer

    PubMed Central

    Rosa, Daniela D; Medeiros, Lídia RF; Edelweiss, Maria I; Pohlmann, Paula R; Stein, Airton T

    2014-01-01

    Background This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 3. Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks. Objectives To evaluate the effectiveness and safety of platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer. Search methods For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for this update. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence. Data collection and analysis Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes. Main results For this updated version, we identified three additional ongoing trials but no new studies for inclusion. Three trials including 368 evaluable women with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Two trials

  2. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  3. WISP1 Polymorphisms Contribute to Platinum-Based Chemotherapy Toxicity in Lung Cancer Patients

    PubMed Central

    Chen, Juan; Yin, Jiye; Li, Xiangping; Wang, Ying; Zheng, Yi; Qian, Chenyue; Xiao, Ling; Zou, Ting; Wang, Zhan; Liu, Junyan; Zhang, Wei; Zhou, Honghao; Liu, Zhaoqian

    2014-01-01

    Platinum-based chemotherapy toxicity is always one of the serious problems from which lung cancer patients suffer. The genetic polymorphism of WISP1 was revealed to be associated with susceptibility and platinum-based chemotherapy response in our previous studies. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with platinum-based chemotherapy toxicity in lung cancer patients. A total of 412 lung cancer patients were enrolled in this study, and 28 polymorphisms of the WISP1 gene were genotyped by SequenomMassARRAY. We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses. Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity. Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer. Genotypes of WISP1 may be novel and useful biomarkers for predicting platinum-based chemotherapy toxicity in lung cancer patients. PMID:25405734

  4. Non-platinum-based chemotherapy for treatment of advanced gastric cancer: 5-fluorouracil, taxanes, and irinotecan.

    PubMed

    Kang, Byung Woog; Kim, Jong Gwang; Kwon, Oh-Kyoung; Chung, Ho Young; Yu, Wansik

    2014-05-14

    Despite numerous advances in treatment options, advanced gastric cancer (AGC) remains a major public health issue and the leading cause of cancer-related deaths. Cisplatin is one of the most effective broad-spectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil (5FU)-based chemotherapy is generally used for treatment of patients with AGC. However, there is still no consensus on the best regimen for treating AGC. Recently, various new chemotherapeutic agents, including oral 5FU, taxanes, and irinotecan, have been identified as improving the outcomes for AGC when used as a single agent or in combination with non-platinum chemotherapy. Nonetheless, it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC. Accordingly, this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC. PMID:24833869

  5. Non-platinum-based chemotherapy for treatment of advanced gastric cancer: 5-fluorouracil, taxanes, and irinotecan

    PubMed Central

    Kang, Byung Woog; Kim, Jong Gwang; Kwon, Oh-Kyoung; Chung, Ho Young; Yu, Wansik

    2014-01-01

    Despite numerous advances in treatment options, advanced gastric cancer (AGC) remains a major public health issue and the leading cause of cancer-related deaths. Cisplatin is one of the most effective broad-spectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil (5FU)-based chemotherapy is generally used for treatment of patients with AGC. However, there is still no consensus on the best regimen for treating AGC. Recently, various new chemotherapeutic agents, including oral 5FU, taxanes, and irinotecan, have been identified as improving the outcomes for AGC when used as a single agent or in combination with non-platinum chemotherapy. Nonetheless, it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC. Accordingly, this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC. PMID:24833869

  6. The expression of ERCC1 and BRCA1 predicts prognosis of platinum-based chemotherapy in urothelial cancer

    PubMed Central

    Song, Wenhui; Ma, Hongshun

    2016-01-01

    Objective To investigate the expression and clinical significance of ERCC1 and BRCA1 genes in urothelial cancer patients. Methods Forty-two urothelial cancer patients who did not receive platinum-based chemotherapy during January 2009 to May 2013 were enrolled. The expression levels of ERCC1 and BRCA1 were determined by immunohistochemistry and the median survival time (MST) for these patients was calculated. Results ERCC1-positive patients who received oxaliplatin-based chemotherapy had a shorter MST than ERCC1-negative patients (P<0.05), whereas there is no difference of MST between BRCA1-positive and -negative patients. Furthermore, MST in ERCC1 and BRCA1 double-positive patients was shorter than ERCC1 and BRCA1 double-negative patients (P<0.05). The positive expression of ERCC1 had a significant positive correlation with BRCA1 (r=0.313, P=0.044). Conclusion The expression level of ERCC1 may be used as a prognostic marker for urothelial cancer patients who received postoperative adjuvant chemotherapy. PMID:27366083

  7. Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients.

    PubMed

    Yin, Ji-Ye; Li, Xi; Li, Xiang-Ping; Xiao, Ling; Zheng, Wei; Chen, Juan; Mao, Chen-Xue; Fang, Chao; Cui, Jia-Jia; Guo, Cheng-Xian; Zhang, Wei; Gao, Yang; Zhang, Chun-Fang; Chen, Zi-Hua; Zhou, Hui; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-07-10

    In this study, we aimed to establish a platinum-based chemotherapy response and toxicity prediction model in advanced non-small cell lung cancer (NSCLC) patients. 416 single nucleotide polymorphisms (SNPs) in 185 genes were genotyped, and their association with drug response and toxicity were estimated using logistic regression. Nine data mining techniques were employed to establish the prediction model; the sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curve were used to assess the models' performance. Finally, selected models were validated in an independent cohort. The models established by naïve Bayesian algorithm had the best performance. The response prediction model achieved a sensitivity of 0.90 and a specificity of 0.47 with the ROC area under curve (AUC) of 0.80. The overall toxicity prediction model achieved a sensitivity of 0.86 and a specificity of 0.46 with the ROC AUC of 0.73. The hematological toxicity prediction model achieved a sensitivity of 0.89 and a specificity of 0.39 with the ROC AUC of 0.76. The gastrointestinal toxicity prediction model achieved a sensitivity of 0.93 and a specificity of 0.35 with the ROC AUC of 0.80. In conclusion, we provided platinum-based chemotherapy response and toxicity prediction models for advanced NSCLC patients. PMID:27126360

  8. Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

    PubMed Central

    Cimino, George D; Pan, Chong-xian; Henderson, Paul T

    2013-01-01

    The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

  9. A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

    PubMed Central

    Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

    2015-01-01

    Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

  10. Epoetin Theta in Anaemic Cancer Patients Receiving Platinum-Based Chemotherapy: A Randomised Controlled Trial

    PubMed Central

    Tjulandin, Sergei A; Bias, Peter; Elsässer, Reiner; Gertz, Beate; Kohler, Erich; Buchner, Anton

    2010-01-01

    Introduction Recombinant human erythropoietin (r-HuEPO) is used to treat symptomatic anaemia due to chemotherapy. A new r-HuEPO, Epoetin theta (Eporatio®), was investigated and compared to placebo and Epoetin beta in a randomised, double-blind clinical trial in adult cancer patients receiving platinum-based chemotherapy, using a fixed weekly starting dose of 20,000 IU Epoetin theta. The primary efficacy endpoint was the responder rate (complete Hb response, Hb increase ≥ 2 g/dL). Research Design and Methods 223 patients were randomised to s.c. treatment for 12 weeks with either Epoetin theta (n = 76) once per week, Epoetin beta (n = 73) three times per week or placebo (n = 74). The starting dose was 20,000 IU once weekly Epoetin theta or 450 IU/kgBW per week Epoetin beta administered in 3 equal weekly doses. Results In the Epoetin theta group were significantly more responders than in the placebo group (65.8 vs. 20.3%, P < 0.0001). Epoetin beta was also more effective than placebo (71.2 vs. 20.3%, P < 0.0001). The mean weekly dose at the time of complete Hb response was lower in the Epoetin theta group (30,000 IU) than in the Epoetin beta group (42,230 IU). Epoetin theta was clearly more effective than placebo. Conclusion This small study showed, that Epoetin theta is a safe and effective treatment of symptomatic anaemia due to platinum-based chemotherapy in cancer patients. PMID:21331363

  11. Platinum-based chemotherapy in triple-negative advanced breast cancer.

    PubMed

    Villarreal-Garza, Cynthia; Khalaf, Daniel; Bouganim, Nathaniel; Clemons, Mark; Peña-Curiel, Omar; Baez-Revueltas, Berenice; Kiss, Alexander; Kassam, Farah; Enright, Katherine; Verma, Sunil; Pritchard, Kathleen; Myers, Jeff; Dent, Rebecca

    2014-08-01

    The purpose of this study was to evaluate the efficacy of platinum-based chemotherapy (PBC) versus conventional non-PBC regimens in a metastatic triple-negative breast cancer (TNBC) setting. We reviewed the electronic patient records of patients with confirmed metastatic TNBC at four major cancer centres in Canada. All patients were allocated into two groups based on type of chemotherapy received (PBC vs. non-PBC) and line of treatment (first-, second-, or third-line). The primary objective of this study was to evaluate the efficacy of PBC in metastatic TNBC in terms of median duration of overall survival (OS) from diagnosis of distant metastatic disease and compare it with the efficacy of conventional non-platinum-based chemotherapy in metastatic TNBC after controlling for known prognostic factors. A total of 153 metastatic TNBC patients were identified, 58 treated with PBC and 95 with non-PBC. The median time in first-line PBC versus non-PBC was not different between the two groups (2 vs. 2 months, p = 0.9), the median time on treatment in second and third-line therapy was longer for the PBC group compared to the conventional treated group (4 vs. 1 months, p = 0.004; 4 vs. 0.5 months, p = 0.004, respectively). Patients who received PBC had a longer OS compared to those managed conventionally (14.5 vs. 10 months, p = 0.041). This study evaluates the survival outcomes in a homogenous group of TNBC metastatic patients treated with or without PBC. Our results confirmed our hypothesis of a better OS among PBC-treated TNBC patients compared to conventionally managed TNBC patients. Currently ongoing Phase III trials assessing the benefit of PBC versus other chemotherapeutic regimens in advanced TNBC will help define the role of these agents for the management of this breast cancer subtype. PMID:25001611

  12. Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery.

    PubMed Central

    Childs, W. J.; Goldstraw, P.; Nicholls, J. E.; Dearnaley, D. P.; Horwich, A.

    1993-01-01

    A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy. With a follow-up of 11 to 117 months (median 41 months) all seven patients with seminoma remain alive and disease free giving an overall survival of 100%. Eleven patients had malignant non seminoma; following chemotherapy eight of these had elective surgical resection of residual mediastinal masses. Complete remission was achieved in nine (82%) patients, however, one of these patients died from bleomycin pneumonitis. With a follow-up of 12 to 113 months (median 55 months) eight of 11 (73%) patients with malignant mediastinal teratoma remain alive and disease free. PMID:8494705

  13. Randomized Pharmacokinetic Study Comparing Subcutaneous and Intravenous Palonosetron in Cancer Patients Treated with Platinum Based Chemotherapy

    PubMed Central

    Sadaba, Belen; del Barrio, Anabel; Campanero, Miguel Angel; Azanza, Jose Ramon; Gomez-Guiu, Almudena; Lopez-Picazo, Jose Maria; Algarra, Salvador Martin; Grimá, Francisco Guillén; Prieto, Maria Blanco

    2014-01-01

    Background Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. Patients and Methods Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0–24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA). Results From October 2009 to July 2010, 25 evaluable patients were included. AUC0–24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69–168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. Conclusions Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy. Trial Registration ClinicalTrials.gov NCT01046240 PMID:24587006

  14. [Rectal cancer and adjuvant chemotherapy: which conclusions?].

    PubMed

    Bachet, J-B; Rougier, P; de Gramont, A; André, T

    2010-01-01

    Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the "historical studies" of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study suggest that adjuvant chemotherapy with fluoropyrimidines (intravenous or oral), in absence of pre-operative treatment, decrease the risk of metastatic relapse after curative surgery for a rectal cancer of stage II or III. This benefice seems similar to the one observed in colon cancer. In the EORTC radiotherapy group trial 22921, an adjuvant chemotherapy with 5-fluorouracil and low dose of leucovorin was not associated with a significantly improvement of overall survival but, despite the fact that only 42.9% of patients received all planed cycles, the progression free survival was increased (not significantly) in groups receiving adjuvant chemotherapy. The French recommendations are to discuss the indication of adjuvant chemotherapy by fluoropyrimidines in cases of stage III rectal cancer on histopathologic reports and no chemotherapy in case of stade II. Despite the fact that none study have assessed a combination of fluoropyrimidines and oxaliplatin in adjuvant setting in rectal cancer, like in colon cancer, the Folfox4, modified Folfox6 or Xelox regimens are valid options in stage III (experts opinion). In cases of pathologic complete remission or in absence of involved nodes, the benefice of adjuvant chemotherapy is not assessed. In

  15. An Adsorptive Transfer Technique Coupled with Brdicka Reaction to Reveal the Importance of Metallothionein in Chemotherapy with Platinum Based Cytostatics

    PubMed Central

    Krizkova, Sona; Fabrik, Ivo; Huska, Dalibor; Adam, Vojtech; Babula, Petr; Hrabeta, Jan; Eckschlager, Tomas; Pochop, Pavel; Darsova, Denisa; Kukacka, Jiri; Prusa, Richard; Trnkova, Libuse; Kizek, Rene

    2010-01-01

    The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug. PMID:21614176

  16. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    PubMed

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  17. Phase II study of gemcitabine plus S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy

    PubMed Central

    Peng, PeiJian; Ou, XueQing; Liao, Hai; Liu, YuMeng; Wang, SiYang; Cheng, ZhiBin; Lin, Zhong

    2016-01-01

    Purpose: No standard salvage regimen has been established for patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) and disease progression after prior platinum-based chemotherapy. This phase II study was designed to evaluate the efficacy and safety of gemcitabine plus S-1 (GS) chemotherapy as a remedial regimen in this setting. Methods: In this multicenter phase II study, 49 patients with recurrent and metastatic NPC who failed previous platinum-based chemotherapy received gemcitabine (1.0 g/m2 on days 1 and 8) plus oral S-1 chemotherapy (twice daily from day 1 to 14). Each cycle was repeated every 3 weeks for two cycles at least. The dose of S-1 was determined according to the body surface area (BSA): 40 mg twice a day for BSA <1.25 m2; 50 mg twice a day for 1.25 m2 ⩽ BSA <1.5 m2; and 60 mg twice a day for BSA ⩾1.5 m2. Results: Treatment was generally well-tolerated. A total of seven patients (14.3%) had grade 3 toxicities and the main toxicity was myelosuppression, whereas the nonhematology adverse events were minimal. There were 3 complete responses (6.4%), 17 partial responses (36.2%), and the overall response rate was 42.6% (95% confidence interval: 27.3–61.2). Median time to progression was 5.8 months and median survival was 14.8 months. The 1- and 2-year survival rates were 64% and 30%, respectively. Conclusions: Gemcitabine plus S-1 offers a satisfactory clinical activity and an acceptable safety profile for recurrent and metastatic NPC patients after failure of platinum-based chemotherapy. PMID:27239233

  18. PTEN polymorphisms contribute to clinical outcomes of advanced lung adenocarcinoma patients treated with platinum-based chemotherapy.

    PubMed

    Yang, Yang; Xu, Wen; Liu, Di; Ding, Xi; Su, Bo; Sun, Yifeng; Gao, Wen

    2016-06-01

    This study aimed to elucidate the impact of PTEN single nucleotide polymorphism (SNP) on clinical outcomes for advanced lung adenocarcinoma (LAC) patients treated with platinum-based chemotherapy. Three functional SNPs (rs11202607 G>A, rs701848 A>G, and rs11202592 G>C) of PTEN gene were genotyped by using DNA from blood samples of 618 advanced LAC patients, and their relationships with clinical outcomes were analyzed. The carriers of homozygous mutant of rs701848 and rs11202592 polymorphisms revealed significantly worse overall survival (OS) than those with heterozygote or wild-type homozygote (18.83 vs. 21.47 vs. 24.37 months, P = 0.034 and 13.40 vs. 19.03 vs. 21.90 months, P = 0.025, respectively). Subgroup analysis revealed that this association was particularly significant in tumor-lymph-node metastasis (TNM) stage III patients. The objective response rates (ORR) and disease control rates (DCR) of patients with genotype AA, AG, and GG in PTEN rs701848 polymorphism were statistically different (24.1 vs 16.6 vs 12.2 %, P = 0.017 and 82.7 vs 76.0 vs 70.2 %, P = 0.029, respectively). Haplotype analysis revealed a protective effect of the haplotype G-A-A (in the order of rs11202592, rs701848, and rs11202607) on chemotherapy efficacy and survival. Taken together, PTEN polymorphisms may contribute to survival and chemotherapy efficacy of advanced LAC patients treated with platinum-based agents. PMID:26695147

  19. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    PubMed

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P < 0.0001). We further built a least absolute shrinkage and selection operator (LASSO)-Cox proportional hazards model that stratified patients into early relapse and late relapse groups (P = 0.00013). The top proteomic features indicative of platinum response were involved in ATP synthesis pathways and Ran GTPase binding. Overall, we demonstrated that proteomic profiles of ovarian serous carcinoma patients predicted platinum drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  20. Psychosocial and Physical Effects of Adjuvant Chemotherapy

    PubMed Central

    Hislop, Thomas Gregory; Elwood, J. Mark; Waxler-Morrison, Nancy; Ragaz, Joseph; Skippen, Diane Hazel; Turner, I.D.

    1991-01-01

    Breast cancer patients younger than 55 completed a questionnaire on psychosocial factors and physical side effects shortly after diagnosis and 9 to 15 months after diagnosis. Those who had used adjuvant chemotherapy were more likely than those who had not to report physical side effects; there was little difference in psychosocial factors. Recent users were more likely than ex-users to report physical side effects, difficulties with domestic chores, and improvement in psychosocial factors. PMID:21229020

  1. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response.

    PubMed

    Gong, Wei-Jing; Yin, Ji-Ye; Li, Xiang-Ping; Fang, Chao; Xiao, Di; Zhang, Wei; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

    2016-06-01

    Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based

  2. Decreased ERCC1 Expression After Platinum-Based Neoadjuvant Chemotherapy in non-Small Cell Lung Cancer.

    PubMed

    Podmaniczky, Eszter; Fábián, Katalin; Pápay, Judit; Puskás, Rita; Gyulai, Márton; Furák, József; Tiszlavicz, László; Losonczy, György; Tímár, József; Moldvay, Judit

    2015-04-01

    We have already demonstrated in a small cohort of 17 non-small cell lung cancer patients that ERCC1 (excision repair cross-complementation group 1) protein expression decreased after platinum-based treatment, however, certain clinicopathological parameters, such as histologic subtypes, ERCC1 expression scores, chemotherapeutic combinations, response rate, gender and smoking history were not analyzed. The aim of our present study was to extend the studied cohort and analyze those parameters. ERCC1 protein expression was examined in 46 patients treated with neoadjuvant chemotherapy. 46 bronchoscopic biopsy samples (27 squamous cell carcinomas /SCC/ and 19 adenocarcinomas /ADC/) together with their corresponding surgical biopsies were studied. ERCC1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. Staining scores were calculated by multiplying the percentage of positive tumor cells (0-100) by the staining intensity (0-3). 24/27 bronchoscopic SCC tissues expressed ERCC1. Thirteen of these cases became negative after neoadjuvant therapy and the expression differences between pre- and postchemotherapy samples were highly significant (p < 0.001). 11/19 bronchoscopic ADC tissues expressed ERCC1. Six of these cases became negative after neoadjuvant therapy and the expression differences were significant (p < 0.010). There was no newly expressed ERCC1 postoperatively. Comparison of staining score changes revealed more pronounced decrease in SCC (p = 0.032). We observed no correlation between initial ERCC1 level or ERCC1 decrease and overall survival, but we demonstrated correlations between decrease in ERCC1 expression and histologic subtypes of tumors and gender. We could confirm our previous data in a larger cohort that platinum-based chemotherapy affects the ERCC1 expression probably referring to an induction of tumor cell selection. PMID:25194563

  3. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    PubMed

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  4. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  5. Icotinib versus docetaxel used in lung adenocarcinoma patients who failed platinum-based chemotherapy: a retrospective study

    PubMed Central

    He, Wei; Zhang, Yan; Xiong, Yu; Dai, Feng-juan; Fan, Qing-xia

    2016-01-01

    Background The efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors have been studied worldwide. However, there are few reports directly comparing the efficacy and safety between icotinib and docetaxel as second-line treatment in lung adenocarcinoma patients who have failed platinum-based chemotherapy. This article offers insight into this field. Methods A total of 137 patients with stage III or IV lung adenocarcinoma who had progressed on first-line platinum-based therapies and received icotinib or docetaxel therapy between October 2011 and February 2013 were retrospectively reviewed. Patients in the icotinib group received oral icotinib at a dose of 125 mg tid, while patients in the docetaxel group received infusion docetaxel at a dose of 75 mg/m2 on day 1 of every 21 days (four to six cycles) until disease progression or unacceptable toxicity occurred after which best supportive care was given. Results There was no statistically significant difference in the objective response rate (23.3% vs 12.5%, P=0.103), progression-free survival (121 days vs 106 days, P=0.083), and overall survival (307 days vs 254 days, P=0.070) between the two groups. As compared to the docetaxel group, the disease control rate (75.3% vs 54.7%, P=0.011) was significantly better in the icotinib group. In the icotinib group, the most common adverse events were rash (35.62%) and diarrhea (24.66%), whereas in the docetaxel group, elevation of transaminase (37.50%), leukopenia (50.00%), and anemia (54.69%) were the most common. Conclusion Icotinib had similar efficacy and a lower adverse events rate in epidermal growth factor receptor-unselected patients as compared to docetaxel, thereby making it an effective second-line therapy option for lung adenocarcinoma.

  6. A common polymorphism in the 5' UTR of ERCC5 creates an upstream ORF that confers resistance to platinum-based chemotherapy.

    PubMed

    Somers, Joanna; Wilson, Lindsay A; Kilday, John-Paul; Horvilleur, Emilie; Cannell, Ian G; Pöyry, Tuija A A; Cobbold, Laura C; Kondrashov, Alexander; Knight, John R P; Puget, Stéphanie; Grill, Jacques; Grundy, Richard G; Bushell, Martin; Willis, Anne E

    2015-09-15

    We show that a common polymorphic variant in the ERCC5 5' untranslated region (UTR) generates an upstream ORF (uORF) that affects both the background expression of this protein and its ability to be synthesized following exposure to agents that cause bulky adduct DNA damage. Individuals that harbor uORF1 have a marked resistance to platinum-based agents, illustrated by the significantly reduced progression-free survival of pediatric ependymoma patients treated with such compounds. Importantly, inhibition of DNA-PKcs restores sensitivity to platinum-based compounds by preventing uORF1-dependent ERCC5 expression. Our data support a model in which a heritable 5' noncoding mRNA element influences individuals' responses to platinum-based chemotherapy. PMID:26338418

  7. A common polymorphism in the 5′ UTR of ERCC5 creates an upstream ORF that confers resistance to platinum-based chemotherapy

    PubMed Central

    Somers, Joanna; Wilson, Lindsay A.; Kilday, John-Paul; Horvilleur, Emilie; Cannell, Ian G.; Pöyry, Tuija A.A.; Cobbold, Laura C.; Kondrashov, Alexander; Knight, John R.P.; Puget, Stéphanie; Grill, Jacques; Grundy, Richard G.; Bushell, Martin; Willis, Anne E.

    2015-01-01

    We show that a common polymorphic variant in the ERCC5 5′ untranslated region (UTR) generates an upstream ORF (uORF) that affects both the background expression of this protein and its ability to be synthesized following exposure to agents that cause bulky adduct DNA damage. Individuals that harbor uORF1 have a marked resistance to platinum-based agents, illustrated by the significantly reduced progression-free survival of pediatric ependymoma patients treated with such compounds. Importantly, inhibition of DNA-PKcs restores sensitivity to platinum-based compounds by preventing uORF1-dependent ERCC5 expression. Our data support a model in which a heritable 5′ noncoding mRNA element influences individuals’ responses to platinum-based chemotherapy. PMID:26338418

  8. Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.

    PubMed

    Williams, J I; Weitman, S; Gonzalez, C M; Jundt, C H; Marty, J; Stringer, S D; Holroyd, K J; Mclane, M P; Chen, Q; Zasloff, M; Von Hoff, D D

    2001-03-01

    Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor. PMID:11297269

  9. Update on Adjuvant Chemotherapy for Early Breast Cancer

    PubMed Central

    Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

    2014-01-01

    Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come. PMID:25336961

  10. Adjuvant chemotherapy for soft tissue sarcoma.

    PubMed

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  11. Platinum-based chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis of randomized-controlled trials.

    PubMed

    Guan, Xiuwen; Ma, Fei; Fan, Ying; Zhu, Wenjie; Hong, Ruoxi; Xu, Binghe

    2015-09-01

    The aim of this study was to evaluate the benefits of the addition of platinum agents for the treatment of patients with triple-negative breast cancer on the basis of randomized-controlled trials (RCTs). A fully recursive literature search was performed in the Cochrane Controlled Trials Register Databases, Medline, EMBASE, and Chinese Biomedical Literature Database in any language. RCTs were considered for inclusion. Eight randomized-controlled trials totaling 1142 patients were included. The objective response rate was reported in six RCTs, which were divided into two subgroups: palliative chemotherapy for a metastatic setting and neoadjuvant chemotherapy. Using the fixed-effects model, the difference between the platinum-based group and the non-platinum-based group was found to be statistically significant in the overall study [relative risk (RR)=1.36, P<0.00001], the subgroup of palliative chemotherapy (RR=2.42, P<0.00001), and the subgroup of neoadjuvant (RR=1.15, P=0.01). Pathological complete response rates were based on five studies, and the results between the platinum-based group and the non-platinum-based group also reached statistical significance both in the fixed-effects model (RR=1.43, P<0.0001) and in the random-effects model (RR=1.47, P=0.01). The results seemed to yield a better response rate and pathological complete response rate for platinum-based therapy in triple-negative breast cancer. However, because of the heterogeneous nature of primary trial outcomes, caution should be exercised in coming to this conclusion and further research is necessary to support these findings. PMID:26086398

  12. BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer

    PubMed Central

    Stefansson, Olafur A.; Villanueva, Alberto; Vidal, August; Martí, Lola; Esteller, Manel

    2012-01-01

    Germline mutations in the BRCA1 or BRCA2 genes are associated with an increased risk of breast and ovarian cancer development. Both genes are involved in DNA repair, and tumors harboring genetic defects in them are thought to be more sensitive to DNA-damaging agents used in chemotherapy. However, as only a minority of breast and ovarian cancer patients carry BRCA1 or BRCA2 mutations, few patients are likely to benefit from these pharmacogenetic biomarkers. Herein, we show that, in cancer cell lines and xenografted tumors, BRCA1 CpG island promoter hypermethylation-associated silencing also predicts enhanced sensitivity to platinum-derived drugs to the same extent as BRCA1 mutations. Most importantly, BRCA1 hypermethylation proves to be a predictor of longer time to relapse and improved overall survival in ovarian cancer patients undergoing chemotherapy with cisplatin. PMID:23069641

  13. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  14. Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Rong, Biaoxue; Zhao, Chongchong; Gao, Wenlong; Yang, Shuanying

    2015-01-01

    Purpose: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. Methods: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone. PMID:26628952

  15. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

    PubMed Central

    Spugnini, Enrico P; Crispi, Stefania; Scarabello, Alessandra; Caruso, Giovanni; Citro, Gennaro; Baldi, Alfonso

    2008-01-01

    Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultrasonographic exam of the body cavities that evidenced thickening of the mesothelium. A surgical biopsy further substantiated the diagnosis. After drainage of the malignant effusion from the affected cavity, the patients received four cycles of intracavitary CDDP at the dose of 50 mg/m2 every three weeks if dogs or four cycles of intracavitary carboplatin at the dose of 180 mg/m2 (every 3 weeks) if cats, coupled with daily administration of piroxicam at the dose of 0.3 mg/kg. The therapy was able to arrest the effusion in all patients for variable remission times: one dog is still in remission after 3 years, one dog died of progressive disease after 8 months and one cat died due to progressive neoplastic growth after six months, when the patient developed a mesothelial cuirass. The combination showed remarkable efficacy at controlling the malignant effusion secondary to MM in our patients and warrants further investigations. PMID:18577247

  16. Adjuvant chemotherapy in early breast cancer.

    PubMed

    Ejlertsen, Bent

    2016-05-01

    these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS

  17. Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes?

    PubMed

    Canter, Robert J

    2016-10-01

    Since preoperative chemotherapy has been clearly shown to improve outcomes for patients with Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma, practitioners have attempted to extend the use of adjuvant/neoadjuvant chemotherapy to other types of adult soft tissue sarcoma. Given the high risk of distant recurrence and disease-specific death for patients with soft tissue sarcoma tumors larger than 10 cm, these patients should be considered candidates for neoadjuvant chemotherapy as well as investigational therapies. Yet, potential toxicity from cytotoxic chemotherapy is substantial, and there remains little consensus and wide variation regarding the indications for use of chemotherapy in the adjuvant/neoadjuvant setting. PMID:27591503

  18. Early intervention with epoetin beta prevents severe anaemia in lung cancer patients receiving platinum-based chemotherapy: a subgroup analysis of the NeoPrevent study.

    PubMed

    de Castro, Javier; Belda-Iniesta, Cristóbal; Isla, Dolores; Dómine, Manuel; Sánchez, Alfredo; Batiste, Eduard; Barón, Manuel González

    2008-02-01

    The NeoPrevent study showed that early intervention with epoetin beta could prevent severe anaemia in patients with solid tumours receiving platinum-based chemotherapy. An early intervention strategy may be particularly warranted in patients with lung cancer, as anaemia is very common in these patients and can be severe. The purpose of this study was to examine the efficacy and safety of epoetin beta in the subpopulation of patients with lung cancer included in the NeoPrevent study. Patients were enrolled if baseline haemoglobin (Hb) levels were platinum-based chemotherapy. Patients received epoetin beta 150 IU/kg three times weekly, until 4 weeks after last chemotherapy cycle. The anaemia prevention response was measured as the proportion of patients with an Hb response (Hb increase of >1g/dl) plus the proportion whose Hb was maintained at +/-1g/dl of baseline. Quality of life (QoL) was measured using the linear analogue scale assessment. The NeoPrevent study included 255 patients in total, and the results for the 102 patients with lung cancer (non-small-cell lung cancer 64%; small-cell lung cancer 36%) are presented here. The overall anaemia prevention response was 90%, with Hb response in 60% of patients and maintenance of baseline Hb level in 30%. Only 9% of patients required transfusions. QoL improved significantly in patients with Hb response (p<0.01) and was maintained in non-responders (p>or=0.578). Epoetin beta was effective in preventing severe anaemia in lung cancer patients receiving platinum-based chemotherapy. PMID:17875340

  19. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

    PubMed Central

    Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

    2014-01-01

    Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

  20. Predictive Value of XPD Polymorphisms on Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Hu, Jingwen; Ding, Xiangxiang; Jiang, Feng; Yin, Rong; Xu, Lin

    2013-01-01

    Background The correlation between xeroderma pigmentosum group D (XPD) polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt-chemotherapy), is still inconclusive. This meta-analysis was aimed to systematically review published evidence and ascertain the exact role of XPD polymorphisms. Methods Databases of MEDLINE and EMBASE were searched up to April 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according the Newcastle-Ottawa Quality Assessment Scales. The relationship between XPD polymorphisms and response to Pt-chemotherapy and survival was analyzed. Results A total of 22 eligible studies were included and analyzed in this meta-analysis. The overall analysis suggested that the XPD Lys751Gln polymorphism was not associated with response to Pt-chemotherapy or survival. However, the XPD 312Asn allele was significantly associated with poor response to Pt-chemotherapy compared with the Asp312 allele (Asn vs. Asp: OR = 0.435, 95% CI: 0.261–0.726). Additionally, the variant genotype of XPD Asp312Asn polymorphism was associated with favorable survival in Caucasian (AspAsn vs. AspAsp: HR = 0.781, 95% CI: 0.619–0.986) but unfavorable survival in Asian (AspAsn+AsnAsn vs. AspAsp: HR = 1.550, 95% CI: 1.038–2.315). Conclusions These results suggest that XPD Asp312Asn polymorphism may function as a predictive biomarker on platinum-based chemotherapy in NSCLC and further studies are warranted. PMID:23977265

  1. Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

    PubMed

    Sullivan, Ivana; Salazar, Juliana; Majem, Margarita; Pallarés, Cinta; Del Río, Elisabeth; Páez, David; Baiget, Montserrat; Barnadas, Agustí

    2014-10-28

    Genetic variants in DNA repair genes may play a role in the effectiveness of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17 SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2) involved in DNA repair mechanisms and its association with outcome in NSCLC. This prospective study included patients with stages III and IV treated with platinum-based chemotherapy. All patients (n = 161) received cisplatin or carboplatin plus a third-generation drug. Additionally, stage IIIA and IIIB patients (n = 74) received concomitant or sequential radiotherapy. Germline polymorphisms were analyzed using the BioMark system in blood DNA samples. We found that in stage III patients, response was significantly associated with SNPs in ERCC1 and in ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the ERCC2 gene. In stage IV patients, response was associated with a genetic variant in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of the DNA repair mechanisms along with the heterogeneity in the treatment of lung cancer could explain the role of multiple genes as putative biomarkers of patient outcome. PMID:25069034

  2. Adjuvant chemotherapy in elderly patients with breast cancer: key challenges.

    PubMed

    Pondé, Noam; Dal Lago, Lissandra; Azim, Hatem A

    2016-06-01

    Elderly women with early breast cancer (BC) form a heterogeneous and large subgroup (41.8% of women with BC are over 65). Decision making in this subgroup is made more difficult by lack of familiarity with their physical, cognitive and social issues. Adequate management depends on biological factors and accurate clinical evaluation through comprehensive geriatric assessment (CGA). CGA can help to better select and determine potential risks factors for patients who are candidates for adjuvant chemotherapy. It is still recently introduced in geriatric oncology and there is a lack of awareness of its importance. Available data on adjuvant chemotherapy for BC is limited but suggests it can be of benefit for well selected patients, though the risk of short and long-term toxicity is significant. Here we provide a discussion of the key practical issues in decision making in the setting of adjuvant chemotherapy for elderly BC patients. PMID:27010772

  3. Predictive assessment in pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy

    PubMed Central

    Yuan, Zhengrong; Li, Jiao; Hu, Ruiqi; Jiao, Yang; Han, Yingying; Weng, Qiang

    2015-01-01

    Published data have shown inconsistent results about the pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy. This meta-analysis aimed to summarize published findings and provide more reliable association. A total of 53 eligible studies including 7433 patients were included. Patients bearing the favorable TrpTrp and TrpArg genotypes of Arg194Trp were more likely to better response rates to platinum-based chemotherapy compared to those with the unfavorable ArgArg genotype (TrpTrp+TrpArg vs. ArgArg: odds ratio (OR) = 2.02, 95% CI, 1.66–2.45). The GlnGln and GlnArg genotypes of Arg399Gln were significantly associated with the poorer response rates compared to those with the ArgArg genotype (GlnGln +GlnArg vs. ArgArg: OR = 0.68, 95% CI, 0.54–0.86). The GlnGln genotype might be more closely associated with shorter survival time and higher risks of death for patients (GlnGln vs. ArgArg: hazard ratio (HR) = 1.14, 95% CI, 0.75–1.75). Our cumulative meta-analyses indicated a distinct apparent trend toward a better response rate for Arg194Trp, but a poorer response rate in Arg399Gln. These findings indicate a predictive role of XRCC1 polymorphisms in clinical outcomes. The use of XRCC1 polymorphisms as predictive factor of clinical outcomes in personalized chemotherapy treatment requires further verification from large well-designed pharmacogenetics studies. PMID:26585370

  4. Efficacy of tamoxifen in combination with docetaxel in patients with advanced non-small-cell lung cancer pretreated with platinum-based chemotherapy.

    PubMed

    Wen, Shimin; Fu, Xi; Li, Guangming; He, Lang; Zhao, Caixia; Hu, Xin; Pan, Rongqiang; Guo, Cuihua; Zhang, Xinping; Hu, Xingsheng

    2016-06-01

    The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression-free survival, overall survival, and safety were evaluated on an intention-to-treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance. PMID:26882453

  5. PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer

    PubMed Central

    Papadaki, C; Sfakianaki, M; Lagoudaki, E; Giagkas, G; Ioannidis, G; Trypaki, M; Tsakalaki, E; Voutsina, A; Koutsopoulos, A; Mavroudis, D; Georgoulias, V; Souglakos, J

    2014-01-01

    Background: Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated. Methods: Quantitative real-time PCR was used to assess the expression of PKM2 in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy. PKM2 mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens. Results: In the training set, high PKM2 mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months vs 6.4, P=0.006), overall survival (OS; 10.1 vs 17.0 months, P=0.01) and disease control rate (DCR; 57.7% vs 74.3% P=0.021) compared to patients with low PKM2 levels. In the validation set, high PKM2 mRNA levels were also associated with deceased PFS (3.7 vs 5.9 months, P=0.006), OS (8.3 vs 16.8 months, P=0.003) and DCR (57.7% vs 70.9% P=0.049) compared to those with low PKM2 mRNA levels. There was no correlation between the PKM2 mRNA levels and the PFS (5.6 vs 5.9, P=0.43) or the OS (9.8 vs 10.1, P=0.51) in the control group. Multivariate analysis revealed high PKM2 mRNA expression as an independent predictive factor for the poor patients' outcome. Conclusions: PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy. PMID:25233397

  6. Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity

    PubMed Central

    Hu, Lei; Chen, Shu-Hui; Lv, Qiao-Li; Sun, Bao; Qu, Qiang; Qin, Chong-Zhen; Fan, Lan; Guo, Ying; Cheng, Lin; Zhou, Hong-Hao

    2016-01-01

    Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients. PMID:27249003

  7. XRCC3 Thr241Met Is Associated with Response to Platinum-Based Chemotherapy but Not Survival in Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Ding, Xiangxiang; Hu, Jingwen; Jiang, Feng; Xu, Lin; Yin, Rong

    2013-01-01

    Background A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC), while the conclusion is still conflicting. Materials and Methods We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to estimate the association strength. Results A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116–1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087–2.004, Pheterogeneity = 0.696). This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929–1.261, Pheterogeneity = 0.564), and there was no difference between Asian and Caucasian population. Conclusions These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism. PMID:24116196

  8. Genetic polymorphism of GSTP1 and ERCC1 correlated with response to platinum-based chemotherapy in non-small cell lung cancer.

    PubMed

    Lv, Hongying; Han, Ting; Shi, Xiaoli; Yao, Yasai; Yao, Yongru; Qiu, Wensheng; Yue, Lu; Liang, Jun

    2014-08-01

    The study aims to investigate whether the glutathione S transferase P1 (GSTP1) and excision repair cross-complementing group 1 (ERCC1) polymorphism influence the response to treatment with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer. Ninety-one patients with metastatic non-small lung cancer were evaluated. Blood samples were obtained from each patient before chemotherapy. They are all administered modified TP, GP, NP regimens. Curative effects in patients were evaluated after at least two cycles of treatment. TTP was calculated. The response rate of GSTP1 with G/G + G/A group and A/A group is 54.55 % (24/44) and 21.28 % (10/47) (P = 0.001), respectively. The response rate of ERCC1 with C/C group and C/T + T/T group is 51.11 % (23/45) and 23.91 % (11/46) (P = 0.007), respectively. Patients with both G/G + G/A and C/C has the response rate of 64.52 % (20/31) (P = 0.000). Logistic regression analysis shows a significant increased chance of treatment response in patients with G/G + G/A genotype versus A/A genotype (P = 0.008) and with T/T + C/T genotype versus C/C genotype (P = 0.001). The median TTP of all patients is 7.32 months. The TTP of individuals with G/G + G/A genotype is 9.56 months, and those with A/A genotype had an TTP of 5.23 months. The TTP of individuals with C/C genotype is 9.16 months, and those with T/T + C/T genotype is 5.53 months. Kaplan-Meier analysis shows that ERCC1 and GSTP1 polymorphisms are correlated with TTP. The log-rank test is was marginally significant (P < 0.01). GSTP1 and ERCC1 polymorphism are correlated with response to platinum-based chemotherapy and have prognostic value for TTP. PMID:24958519

  9. In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers

    PubMed Central

    Lu, Qing-Bin; Zhang, Qin-Rong; Ou, Ning; Wang, Chun-Rong; Warrington, Jenny

    2015-01-01

    Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers. PMID:26351651

  10. Optimizing adjuvant chemotherapy in early-stage breast cancer.

    PubMed

    Perez, Edith; Muss, Hyman B

    2005-12-01

    Mortality in breast cancer has declined in the past decade, owing to advances in diagnosis, surgery, radiotherapy, and systemic treatments. Adjuvant chemotherapy has had a major effect on increasing survival in women with locoregional breast cancer. Like all treatments, adjuvant chemotherapy is a work in progress, and it has evolved from single oral agents to complex multidrug regimens. The choice of regimens is not without controversy, however, and several have been shown to be more effective than others, especially in patients who are at high risk for recurrence. The taxanes paclitaxel and docetaxel (Taxotere) have been shown to be effective in the adjuvant setting, and they have also been shown to improve the outcomes in node-positive disease. Both disease-free and overall survival are greater with doxorubicin, paclitaxel, and cyclophosphamide given in a dose-dense, every-2-week schedule with growth factor support than with the same agents given in an every-3-week schedule. Disease-free and overall survival in patients with node-positive disease are greater with docetaxel, doxorubicin (Adriamycin), and cyclophosphamide (TAC) than with fluorouracil, doxorubicin, and cyclophosphamide (FAC). Febrile neutropenia is common with the TAC regimen, but it can be minimized with growth factor support. Based on these findings, dose-dense therapy and TAC are the current adjuvant treatments of choice in patients with node-positive disease; other, less-intense regimens may be appropriate in patients with lower-risk disease. Ongoing trials are investigating the efficacy of commonly used regimens, new chemotherapeutic and biologic agents, and novel doses and schedules of currently available agents. PMID:16506631

  11. The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients.

    PubMed

    Hurley, Judith; Reis, Isildinha M; Rodgers, Steven E; Gomez-Fernandez, Carmen; Wright, Jean; Leone, Jose Pablo; Larrieu, Rene; Pegram, Mark D

    2013-04-01

    Triple-negative breast cancers comprise about 20 % of breast cancers. They have poor prognosis and have no standard therapy. The aim of this study was to evaluate pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based chemotherapy. This is a retrospective study of one hundred and forty-four women with TNBC treated with neoadjuvant platinum-containing chemotherapy for locally advanced breast cancer at the University of Miami between January 1, 1999, and January 1, 2011. The medical record was reviewed to obtain data on clinical characteristics, including ethnicity, race, age, clinical stage, treatment regimen, and vital status. This study was approved by the University of Miami IRB. All patients had locally advanced breast cancer with at least one of the following features at presentation: T3, T4, N2, and N3. The mean tumor size by palpation was 9.4 cm. The clinical T-stage at presentation was 1.4 % T1, 8.3 % T2, 52.8 % T3, and 37.5 % T4 (19.4 % T4d). The nodal status by physical exam at presentation was 23 % N0, 37.5 % N1, 34 % N2, and 5.5 % N3. pCR in breast and axilla was seen in 31 %. PFS and OS were 55 and 59 %, respectively, at 7 years. Cisplatin offered a survival advantage over carboplatin in both PFS (P = 0.007) and OS (P = 0.018). Node positivity was the most important predictor of survival. Cisplatin/docetaxel neoadjuvant therapy was well tolerated and an effective therapy in locally advanced TNB. PMID:23542956

  12. A Significant Statistical Advancement on the Predictive Values of ERCC1 Polymorphisms for Clinical Outcomes of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: An Updated Meta-Analysis

    PubMed Central

    Han, Yali; Liu, Jie; Sun, Meili; Zhang, Zongpu; Liu, Chuanyong; Sun, Yuping

    2016-01-01

    Background. There is no definitive conclusion so far on the predictive values of ERCC1 polymorphisms for clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We updated this meta-analysis with an expectation to obtain some statistical advancement on this issue. Methods. Relevant studies were identified by searching MEDLINE, EMBASE databases from inception to April 2015. Primary outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). All analyses were performed using the Review Manager version 5.3 and the Stata version 12.0. Results. A total of 33 studies including 5373 patients were identified. ERCC1 C118T and C8092A could predict both ORR and OS for platinum-based chemotherapy in Asian NSCLC patients (CT + TT versus CC, ORR: OR = 0.80, 95% CI = 0.67–0.94; OS: HR = 1.24, 95% CI = 1.01–1.53) (CA + AA versus CC, ORR: OR = 0.76, 95% CI = 0.60–0.96; OS: HR = 1.37, 95% CI = 1.06–1.75). Conclusions. Current evidence strongly indicated the prospect of ERCC1 C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients. However, the results should be interpreted with caution and large prospective studies are still required to further investigate these findings. PMID:27057082

  13. Overexpression of the epithelial cell adhesion molecule is associated with a more favorable prognosis and response to platinum-based chemotherapy in ovarian cancer

    PubMed Central

    Woopen, Hannah; Pietzner, Klaus; Richter, Rolf; Fotopoulou, Christina; Joens, Thomas; Braicu, Elena Ioana; Mellstedt, Håkan; Mahner, Sven; Lindhofer, Horst; Darb-Esfahani, Silvia; Denkert, Carsten

    2014-01-01

    Objective Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). Methods EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. Results Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). Conclusion Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings. PMID:25045435

  14. Efficacy and safety of extended use of platinum-based doublet chemotherapy plus endostatin in patients with advanced nonsmall cell lung cancer.

    PubMed

    Hu, Weiheng; Fang, Jian; Nie, Jun; Dai, Ling; Zhang, Jie; Chen, Xiaoling; Ma, Xiangjuan; Tian, Guangming; Wu, Di; Han, Sen; Han, Jindi; Wang, Yang; Long, Jieran

    2016-07-01

    The aim of this study was to investigate the efficacy and safety of the extended use of platinum-based doublet chemotherapy (PT-DC) plus endostatin in patients with advanced nonsmall cell lung cancer (NSCLC).We performed a retrospective analysis of 200 newly diagnosed advanced NSCLC patients who had received at least 1 cycle of endostatin plus PT-DC between September 2009 and November 2014. Of these patients, 155 received 4 or more cycles of therapy (the extended therapy group), while 45 received less than 4 cycles of therapy (the control group). Clinical tumor responses, progression-free survival (PFS), overall survival (OS), and toxicity profiles were recorded and retrospectively analyzed.In the extended therapy group, 67 patients (43.2%) achieved a best overall response rate of partial response (PR), while in the control group, 13 patients (28.9%) had a best overall response rate of PR. After a median follow-up of 15.9 months, the median PFS and OS were 8.0 and 23.1 months in the extended arm and 5.8 and 14.0 months in the control arm, respectively. There were statistically significant differences in median PFS and OS between these 2 arms. Hematologic and gastrointestinal toxicities occurred more frequently in the extended therapy group, but no statistically significant difference was detected in grade 3 to 4 toxicities overall between these 2 groups.In conclusion, extended treatment using endostatin combined with PT-DC can provide additional survival benefits and satisfactory toxicity profiles in previously untreated patients with NSCLC, which merits further evaluation in a larger prospective study. PMID:27428214

  15. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    PubMed Central

    Zhang, Jian-Wei; Zhao, Yuan-Yuan; Guo, Ying; Xue, Cong; Hu, Zhi-Huang; Huang, Yan; Zhao, Hong-Yun; Zhang, Jing; Wu, Xuan; Fang, Wen-Feng; Ma, Yu-Xiang; Zhang, Li

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations (r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy. PMID:23816558

  16. Efficacy and safety of extended use of platinum-based doublet chemotherapy plus endostatin in patients with advanced nonsmall cell lung cancer

    PubMed Central

    Hu, Weiheng; Fang, Jian; Nie, Jun; Dai, Ling; Zhang, Jie; Chen, Xiaoling; Ma, Xiangjuan; Tian, Guangming; Wu, Di; Han, Sen; Han, Jindi; Wang, Yang; Long, Jieran

    2016-01-01

    Abstract The aim of this study was to investigate the efficacy and safety of the extended use of platinum-based doublet chemotherapy (PT-DC) plus endostatin in patients with advanced nonsmall cell lung cancer (NSCLC). We performed a retrospective analysis of 200 newly diagnosed advanced NSCLC patients who had received at least 1 cycle of endostatin plus PT-DC between September 2009 and November 2014. Of these patients, 155 received 4 or more cycles of therapy (the extended therapy group), while 45 received less than 4 cycles of therapy (the control group). Clinical tumor responses, progression-free survival (PFS), overall survival (OS), and toxicity profiles were recorded and retrospectively analyzed. In the extended therapy group, 67 patients (43.2%) achieved a best overall response rate of partial response (PR), while in the control group, 13 patients (28.9%) had a best overall response rate of PR. After a median follow-up of 15.9 months, the median PFS and OS were 8.0 and 23.1 months in the extended arm and 5.8 and 14.0 months in the control arm, respectively. There were statistically significant differences in median PFS and OS between these 2 arms. Hematologic and gastrointestinal toxicities occurred more frequently in the extended therapy group, but no statistically significant difference was detected in grade 3 to 4 toxicities overall between these 2 groups. In conclusion, extended treatment using endostatin combined with PT-DC can provide additional survival benefits and satisfactory toxicity profiles in previously untreated patients with NSCLC, which merits further evaluation in a larger prospective study. PMID:27428214

  17. Adjuvant post-operative chemotherapy in bitches with mammary cancer.

    PubMed

    Karayannopoulou, M; Kaldrymidou, E; Constantinidis, T C; Dessiris, A

    2001-03-01

    The survival time in a group of eight bitches with malignant mammary tumours given adjuvant post-operative chemotherapy was compared with survival in another group of eight bitches with mammary cancer which were treated by surgical excision alone. The same surgical procedure was used in both groups. All bitches had stage III disease according to the World Health Organization clinical staging system. Histologically, 10 of the bitches had complex carcinomas (carcinomatous mixed tumours), the remaining six bitches had carcinosarcomas. The chemotherapeutic protocol used was a combination of 5-fluorouracil (150 mg/m2 of body surface area) and cyclophosphamide (100 mg/m2) given on the same day, intravenously, every week for four consecutive weeks. Chemotherapy was started one week post-surgery. Selected haematological parameters (packed cell volume, white blood cell count, platelet count and differential white blood cell count) and serum biochemical parameters (alanine aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine) were measured before and during chemotherapy. Survival analysis indicated that the chemotherapeutic regimen had a positive influence on the disease-free interval and the survival time of the eight bitches (P < 0.05). Although leucocyte numbers were significantly decreased (P < 0.001) during chemotherapy, the mean leucocyte counts remained within normal limits. Temporary leukopenia was noted only in one bitch. Packed cell volume and alkaline phosphatase increased significantly (P < 0.05) but within normal limits. Creatinine was also increased significantly (P < 0.01) but the mean creatinine concentrations were within normal limits, although in half of the bitches the concentrations occasionally rose above normal. PMID:11315572

  18. [Recent Status of Postoperative Adjuvant Chemotherapy after Completely Resected Lung Cancer].

    PubMed

    Naito, Masahito; Tsuboi, Masahiro

    2016-02-01

    Several landmark study elucidated that adjuvant cisplatin-based chemotherapy for stage II-IIIA non-small cell lung cancer (NSCLC)patients after appropriate surgical resection can significantly improve 5-year survival rate. Meta-analysis of modern cisplatin based adjuvant chemotherapy trial confirmed this benefit. Furthermore, in Japan, large randomized trial and metaanalysis assessing the efficacy of uracil-tegafur(UFT)for stage I patients with completely resected NSCLC reported that UFT can significantly improve 5-year survival rate. Meta-analysis of subgroup assessed that effectiveness of UFT for stage I NSCLC patients with a tumor lager than 2 cm. According to these evidence, cisplatin-based adjuvant chemotherapy for stage II-III A NSCLC and UFT for stage I NSCLC patients with a tumor lager than 2 cm are used standard postoperative adjuvant chemotherapy in Japan. In recent year, it is presumed that personalized care will be necessary to re-evaluate strategies for postoperative adjuvant chemotherapy of lung cancer. Considering histological subtype of lung cancer, several randomize trial for postoperative adjuvant chemotherapy with non-squamous NSCLC or high neuroendocrine tumor of lung are ongoing. In addition, recent studies of biological research indicate that some tumor marker such as ERCC1 may had a predictive value for selecting patients who will derive the benefit from adjuvant chemotherapy. PMID:27067681

  19. HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.

    PubMed

    Zivanovic, Oliver; Abramian, Alina; Kullmann, Maximilian; Fuhrmann, Christine; Coch, Christoph; Hoeller, Tobias; Ruehs, Hauke; Keyver-Paik, Mignon Denise; Rudlowski, Christian; Weber, Stefan; Kiefer, Nicholas; Poelcher, Martin L; Thiesler, Thore; Rostamzadeh, Babak; Mallmann, Michael; Schaefer, Nico; Permantier, Maryse; Latten, Sandra; Kalff, Joerg; Thomale, Juergen; Jaehde, Ulrich; Kuhn, Walther C

    2015-02-01

    This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC. PMID:24895230

  20. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  1. FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy

    PubMed Central

    Suzman, Daniel L.; Blumenthal, Gideon; Mushti, Sirisha; He, Kun; Libeg, Meredith; Keegan, Patricia; Pazdur, Richard

    2016-01-01

    On October 9, 2015, the U.S. Food and Drug Administration expanded the nivolumab metastatic non-small cell lung cancer (NSCLC) indication to include patients with nonsquamous NSCLC after a 3.25-month review timeline. Approval was based on demonstration of an improvement in overall survival (OS) in an international, multicenter, open-label, randomized trial comparing nivolumab to docetaxel in patients with metastatic nonsquamous NSCLC with progression on or after platinum-based chemotherapy. The CheckMate 057 trial enrolled 582 patients who were randomized (1:1) to receive nivolumab or docetaxel. Nivolumab demonstrated improved OS compared with docetaxel at the prespecified interim analysis with a hazard ratio (HR) of 0.73 (p = .0015), and a median OS of 12.2 months (95% CI: 9.7–15.0 months) in patients treated with nivolumab compared with 9.4 months (95% CI: 8.0–10.7 months) in patients treated with docetaxel. A statistically significant improvement in objective response rate (ORR) was also observed, with an ORR of 19% (95% CI: 15%–24%) in the nivolumab arm and 12% (95% CI: 9%–17%) in the docetaxel arm. The median duration of response was 17 months in the nivolumab arm and 6 months in the docetaxel arm. Progression-free survival was not statistically different between arms. A prespecified retrospective subgroup analysis suggested that patients with programmed cell death ligand 1-negative tumors treated with nivolumab had similar OS to those treated with docetaxel. The toxicity profile of nivolumab was consistent with the known immune-mediated adverse event profile except for 1 case of grade 5 limbic encephalitis, which led to a postmarketing requirement study to better characterize immune-mediated encephalitis. Implications for Practice: Based on the results from the CheckMate 057 clinical trial, nivolumab represents a new treatment option for patients requiring second-line treatment for metastatic non-small cell lung cancer. The role of nivolumab in

  2. Racial variation in adjuvant chemotherapy initiation among breast cancer patients receiving oncotype DX testing.

    PubMed

    Roberts, Megan C; Weinberger, Morris; Dusetzina, Stacie B; Dinan, Michaela A; Reeder-Hayes, Katherine E; Troester, Melissa A; Carey, Lisa A; Wheeler, Stephanie B

    2015-08-01

    It is unknown whether racial differences exist in adjuvant chemotherapy initiation among women with similar oncotype DX (ODX) risk scores. We examined whether adjuvant chemotherapy initiation varied by race. Data come from the Phase III, Carolina Breast Cancer Study, a longitudinal, population-based study of North Carolina women diagnosed with breast cancer between 2008 and 2014. We used modified Poisson regression and report adjusted relative risk (aRR) and 95% confidence intervals (95%CI) to estimate the association between race and adjuvant chemotherapy initiation across ODX risk groups among women who received the test (n = 541). Among women who underwent ODX testing, 54.2, 37.5, and 8.3% of women had tumors classified as low-, intermediate-, and high-risk groups, respectively. We observed no racial variation in adjuvant chemotherapy initiation. Increasing ODX risk score (aRR = 1.39, 95%CI = 1.22, 1.58) and being married (aRR = 2.92, 95%CI = 1.12, 7.60) were independently associated with an increased likelihood of adjuvant chemotherapy in the low-risk group. Among women in the intermediate-risk group, ODX risk score (aRR = 1.15, 95%CI = 1.11, 1.20), younger age (aRR = 1.95, 95%CI = 1.35, 2.81), larger tumor size (aRR = 1.70, 95%CI = 1.22, 2.35), and higher income were independently associated with increased likelihood of adjuvant chemotherapy initiation. No racial differences were found in adjuvant chemotherapy initiation among women receiving ODX testing. As treatment decision-making becomes increasingly targeted with the use of genetic technologies, these results provide evidence that test results may drive treatment in a similar way across racial subgroups. PMID:26216535

  3. Adjuvant Chemotherapy Use and Adverse Events among Older Patients with Stage III Colon Cancer

    PubMed Central

    Kahn, Katherine L.; Adams, John L.; Weeks, Jane C.; Chrischilles, Elizabeth A.; Schrag, Deborah; Ayanian, John Z.; Kiefe, Catarina I.; Ganz, Patricia A.; Bhoopalam, Nirmala; Potosky, Arnold L.; Harrington, David P.; Fletcher, Robert H.

    2010-01-01

    Context Randomized trials suggest adjuvant chemotherapy is effective for elderly patients with stage III colon cancer. However, the elderly are less likely to receive this therapy than younger patients, perhaps because of concern about adverse effects. Objective To evaluate adjuvant chemotherapy use and outcomes for older patients with stage III colon cancer from well-defined population-based settings and healthcare systems. Design Observational study of adjuvant chemotherapy use and outcomes by age, using Poisson regression to estimate the number of adverse events adjusted for demographic and clinical factors, including comorbid illness and specific elements of chemotherapy regimens documented with clinically detailed medical record reviews and patient and surrogate surveys. Setting Five geographically defined regions (Alabama, Iowa, Los Angeles County, Northern California, and North Carolina), five integrated health-care delivery systems, and 15 Veterans hospitals. Patients All 675 patients diagnosed with stage III colon cancer during 2003-2005 who underwent surgical resection were followed up to 15 months post-diagnosis. Main outcome measures Chemotherapy regimen, dose, duration and annualized mean number of adverse events stratified by age. Results Half of the 202 patients >=75 years received adjuvant chemotherapy compared with 87% of 473 younger patients (diff 37%, 95% CI 30%-45%). Among adjuvant chemotherapy users, 14 (14%) of patients >=75 years and 178 (44%) of younger patients received a regimen containing oxaliplatin (diff 30%, 95% CI 21%-38%). Older patients were less likely to continue. By 150 days, 99 (40%) patients >= 65 years and 68 (25%) younger patients had discontinued chemotherapy (diff 15%, 95% CI 7%-23%). Overall, 162 (24%) patients had at least one adverse clinical event, with more events among patients treated with vs. without adjuvant chemotherapy (mean 0.394 vs. 0.160, diff 0.234, 95% CI 0.11-0.36, p<0.001). Among adjuvant chemotherapy

  4. Adjuvant chemotherapy of axillary node-negative carcinoma of the breast using doxorubicin and cyclophosphamide.

    PubMed

    Brooks, R J; Jones, S E; Salmon, S E; Chase, E M; Davis, S L; Moon, T E; Giordano, G F; Ketchel, S J; Jackson, R A

    1986-01-01

    One hundred fifty-six women with axillary node-negative breast cancer and primary tumors less than or equal to 5 cm in diameter (T1N0 or T2N0) were treated with a brief course of postoperative adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. Treatment was well tolerated and toxicity was minimal. With a median follow-up time of 58 months, there has been 1 relapse among 58 patients with T1 primary lesions and 15 relapses among 98 patients with T2 primary tumors. When compared with a matched historical control group receiving surgery alone, significant improvement was apparent in disease-free survival among the patients who received adjuvant chemotherapy. Prospective controlled trials are needed if we are to confirm this favorable experience with adjuvant chemotherapy in the treatment of women with node-negative breast cancer. PMID:3534586

  5. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

    PubMed Central

    Yang, Chih-Jen; Tsai, Ming-Ju; Hung, Jen-Yu; Liu, Ta-Chih; Chou, Shah-Hwa; Lee, Jui-Ying; Hsu, Jui-Sheng; Tsai, Ying-Ming; Huang, Ming-Shyan; Chong, Inn-Wen

    2016-01-01

    Background Increased evidences show that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS) compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear. Patients and methods We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy), and overall survival (OS2, the OS in salvage therapy) were recorded. Results Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this study. The overall response rate of second salvage therapy is 13%, and none of them received erlotinib. Patients who received chemotherapy had a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0 months, P=0.1417) but not in OS. Furthermore, patients who received platinum-based doublet had a trend for better PFS2 and a significantly better OS2 than those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months, P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007). Analyses of the patients receiving platinum-based doublet showed that patients receiving pemetrexed had a significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083) and a trend for better OS2 than those without pemetrexed treatment. Conclusion Pemetrexed-based platinum chemotherapy may be the

  6. Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

    PubMed

    Franceschi, E; Bartolotti, M; Paccapelo, A; Marucci, G; Agati, R; Volpin, L; Danieli, D; Ghimenton, C; Gardiman, M P; Sturiale, C; Poggi, R; Mascarin, M; Balestrini, D; Masotto, B; Brandes, A A

    2016-06-01

    The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group). PMID:26940908

  7. Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

    PubMed Central

    You, Kai-Yun; Huang, Rong; Yu, Xin; Liu, Yi-Min; Gao, Yuan-Hong

    2016-01-01

    Abstract The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. We performed a retrospective study of 200 rectal cancer patients who were treated with preoperative chemoradiation and were pathologically graded as ypII and ypIII stages between March 2003 and May 2012. All patients were divided into 2 groups according to the median duration of adjuvant chemotherapy of 2 months. Overall survival (OS) and disease-free survival (DFS) were compared between patients with duration shorter and longer than 2 months in the whole group and subgroups of ypII and ypIII. Recurrence patterns were also analyzed in all subgroups. Multivariate analysis was performed to explore clinical factors that were significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival. In subgroup of ypII stage, the 5-year OS and DFS were similar between patients in long and short durations of adjuvant chemotherapy. For patients of ypIII stage, although no significant difference was found in OS between patients in short and long durations, DFS was showed to be higher in the group of long duration. Further analysis showed that longer duration of adjuvant chemotherapy could lead to improved control of distant metastasis and no impact on local control. Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those

  8. Vascular endothelial growth factor expression correlates with serum CA125 and represents a useful tool in prediction of refractoriness to platinum-based chemotherapy and ascites formation in epithelial ovarian cancer

    PubMed Central

    Wei, Ai-Qun; Robertson, Gregory; Morris, David L.

    2015-01-01

    There is an increasing need for the identification of novel biological markers and potential therapeutic targets in epithelial ovarian cancer (EOC). Given the critical role of growth factors in the biology of EOC, we aimed in the present study to evaluate the intratumoral expressions of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) proteins and their clinical relevance in a cohort of 100 patients with EOC. All patients received platinum-based chemotherapy after surgery. A comparative immunohistochemical study of normal ovarian and EOC tissues showed that both growth factors were expressed at higher levels in tumor samples. In our statistical analysis, while no association existed between the FGF expression status and the clinicopathological characteristics of patients, intratumoral VEGF was identified as a potential biomarker for the prediction of ascites formation. In addition, the expression status of VEGF appeared to independently predict overall survival and response to chemotherapy. Furthermore, a direct association was demonstrated between the pre-treatment VEGF expression and serum CA125 after three cycles of chemotherapy. In sum, we report for the first time to our knowledge the correlation between intratumoral VEGF and serum CA125 in EOC. Our data also shows the prognostic value of VEGF expression in EOC. These results suggest the potential value of intratumoral VEGF in patient stratification. Dual inhibition of VEGF and CA125 might bring about a better outcome for patients with EOC. PMID:26143638

  9. Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies

    PubMed Central

    Bajpai, Jyoti; Susan, Deepa

    2016-01-01

    Soft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. PMID:27169114

  10. Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies.

    PubMed

    Bajpai, Jyoti; Susan, Deepa

    2016-01-01

    Soft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. PMID:27169114

  11. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy

    NASA Technical Reports Server (NTRS)

    Headley, J. A.; Theriault, R. L.; LeBlanc, A. D.; Vassilopoulou-Sellin, R.; Hortobagyi, G. N.

    1998-01-01

    The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

  12. Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer

    PubMed Central

    Kumar, Aalok; Lim, Howard John

    2015-01-01

    Background Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. Methods We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). Results A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88). Conclusions In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed. PMID:26487941

  13. Adjuvant Chemotherapy Following Complete Resection of Soft Tissue Sarcoma in Adults: A Clinical Practice Guideline

    PubMed Central

    Bramwell, Vivien H. C.; Bell, Robert; Davis, Aileen M.; Charette, Manya L.; The members of the cancer care Ontario practice guidelines initiative sarcoma disease site group

    2002-01-01

    Purpose. To review the literature and make recommendations for the use of anthracycline-based adjuvant chemotherapy in adult patients with soft tissue sarcoma (STS). Patients. The recommendations apply to patients >15 years old with completely resected STS. Methods. A systematic overview of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline. Results. Four meta-analyses and 17 randomized clinical trials comparing anthracycline-based adjuvant chemotherapy versus observation were reviewed. The Sarcoma Meta-Analysis Collaboration (SMAC) was the best analysis because it assessed individual patient data and had the longest follow-up. The results of the SMAC meta-analysis together with data from more recently published randomized trials, as well as our analysis of the toxicity and compliance data, are incorporated in this systematic review. Discussion. It is reasonable to consider anthracycline-based adjuvant chemotherapy in patients who have had removal of a sarcoma with features predicting a high likelihood of relapse (deep location, size >5 cm, high histological grade). Although the benefits of adjuvant chemotherapy are most apparent in patients with extremity sarcomas, patients with high-risk tumours at other sites should also be considered for such therapy. PMID:18521341

  14. MYST3/CREBBP Rearranged Acute Myeloid Leukemia after Adjuvant Chemotherapy for Breast Cancer

    PubMed Central

    Patnaik, Mrinal M.; Naina, Harris V.

    2014-01-01

    Although rare, clinicians and patients must be aware that therapy related malignancies, specifically acute myeloid leukemia (AML), can occur as a complication of adjuvant chemotherapy for breast cancer. Vigilance for signs and symptoms is appropriate. AML with t (8;16) is a specific translocation leading to formation of a fusion protein (MYST3/CREBBP). The MYST3/CREBBP AML tends to develop within 2 years of adjuvant chemotherapy, especially for breast cancer, without preceding myelodysplasia. It usually presents with disseminated intravascular coagulation and osteolytic lesions and has a poor prognosis despite aggressive resuscitation and therapy. With the increasing use of adjuvant chemotherapy for breast cancer, we are seeing a definite increase in the incidence of therapy related myelodysplastic syndromes and AML. One must keep this complication in mind while counseling and following up breast cancer patients who have received adjuvant chemotherapy. New osteolytic bone lesions in a patient with history of breast cancer do not necessarily mean metastatic disease and should be fully evaluated. PMID:25548695

  15. Adjuvant chemotherapy for bladder cancer-why does level 1 evidence not support it?

    PubMed

    Raghavan, D; Bawtinhimer, A; Mahoney, J; Eckrich, S; Riggs, S

    2014-10-01

    Neoadjuvant cisplatin-based combination chemotherapy provides a 5% increase in cure rate, an increase in median survival of about 3 years, and statistically significant and clinically relevant increments in overall survival for patients with invasive bladder cancer. Despite compelling level 1 data, it has become quite clear that facts that are similar to those that changed the paradigm of treatment of breast cancer in the 1970s have not had a similar influence on patterns of practice in bladder cancer care. Instead of using this proven approach, cystectomy alone or surgery followed by adjuvant chemotherapy is often used as a functional alternative for patients with deeply invasive and/or node-metastatic disease discovered at radical cystectomy. However, there is no well-powered level 1 evidence to support routine adjuvant chemotherapy for invasive bladder cancer, and some randomized trials have shown inferior outcomes. There is a clear need for a well-designed, randomized trial that tests the utility of adjuvant chemotherapy for invasive bladder cancer, but until that has been completed, neoadjuvant chemotherapy followed by definitive local treatment should be the standard of care for invasive bladder cancer. PMID:24569916

  16. [A Case of Idiopathic Thrombocytopenic Purpura during Adjuvant Chemotherapy for Colon Cancer].

    PubMed

    Takahara, Yoshihiro; Ozawa, Shinichi; Ogasawara, Takeshi; Shida, Takashi; Nomura, Satoru; Sato, Yoshiharu; Takahashi, Makoto

    2015-11-01

    A 76-year-old man underwent surgery for sigmoid colon cancer. The pathological finding was stage Ⅱ with a high-risk of recurrence (SI [bladder], l y0, v2, pN0, H0, P0, M0). He was treated with TS-1 as adjuvant chemotherapy. After the 1 course of chemotherapy, his platelet count was 4,000/mL. The high index of platelet associated IgG (PA-IgG) and bone marrow examination suggested that thrombocytopenia was caused by idiopathic thrombocytopenic purpura. The platelet count improved by prednisolone administration and Helicobacter pylori eradication treatment. After 6 months with no administration of adjuvant chemotherapy, the colon cancer recurred locally, and we performed a Hartmann's operation. PMID:26805292

  17. Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer.

    PubMed

    Verhoeff, S R; van Erning, F N; Lemmens, V E P P; de Wilt, J H W; Pruijt, J F M

    2016-07-01

    Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated. PMID:26914273

  18. Toxicity of (neo)adjuvant chemotherapy for BRCA1- and BRCA2-associated breast cancer.

    PubMed

    Drooger, Jan C; Heemskerk-Gerritsen, Bernadette A M; Smallenbroek, Nyrée; Epskamp, Cynthia; Seynaeve, Caroline M; Jager, Agnes

    2016-04-01

    Treatment with (neo)adjuvant chemotherapy for breast cancer, as currently given, causes cell damage by induction of double-strand DNA breaks. Because BRCA1 and BRCA2 proteins play a role in the repair of DNA damage, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. As a downside, acute chemotherapy-related toxicity may also be increased. We selected all female patients who were treated at the Erasmus MC Cancer Institute, with (neo)adjuvant chemotherapy for primary or locoregional recurrence of breast cancer (PBC/LR) between January 1, 2004 and December 31, 2014. The primary outcome was the relative total dose intensity (RTDI), calculated for anthracyclines and taxanes separately. Secondary outcomes were the occurrence of febrile neutropenia, delay in chemotherapy administration, and switch to another chemotherapy regimen due to toxicity. In total, 701 patients treated for PBC/LR were eligible for data analyses, among which 85 BRCA1/2 mutation carriers (n = 67 BRCA1 and n = 18 BRCA2). The mean RTDI for anthracyclines was not significantly different between both groups (98.7 % in the BRCA1/2, 96.6 % in the sporadic group, p = 0.27). Also the mean RTDI for taxanes was not significantly different between the groups (93.6 % in the BRCA1/2-associated, 90.0 % in the sporadic group, p = 0.12). Linear regression analysis revealed no significant effect of BRCA1/2 mutation carriership on the RTDIs. No significant differences were found in the percentages of patients presenting with febrile neutropenia, having a delay in chemotherapy administration or switching to an altered chemotherapy regimen. Additionally, the odds ratios showed no significant effect of BRCA1/2 mutation carriership on the secondary outcome variables. (Neo)adjuvant chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients suggesting that the DNA damage repair mechanism of non-cancer cells

  19. Adjuvant chemotherapy for older adults with breast cancer: making the standard a standard.

    PubMed

    Pal, Sumanta Kumar; Mortimer, Joanne

    2009-09-01

    Muss HB, Berry DA, Cirrincione CT et al.: Adjuvant chemotherapy in older women with early-stage breast cancer. N. Engl. J. Med. 360, 2055-2065 (2009). To date, only two prospective trials evaluating adjuvant therapy for breast cancer in older adults have been published. The second and more recent trial, Cancer and Leukemia Group B (CALGB) 49907, provides substantial evidence supporting the use of standard adjuvant chemotherapy regimens (doxorubicin-cyclophosphamide or cyclophosphamide-methotrexate-5-fluorouracil) as opposed to simplified oral regimens (capecitabine). In this trial, both the risk of relapse (hazard ratio: 2.09; 95% CI: 1.38-3.17; p < 0.001) and the risk of death (hazard ratio: 1.85; 95% CI: 1.11-3.08; p = 0.02) were significantly higher with capecitabine compared with standard chemotherapy. The current review explores both the implications and potential caveats of this innovative trial. CALGB 49907 represents a paradigm for further studies of adjuvant cancer therapy in older adults. PMID:19702447

  20. The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review.

    PubMed

    Xavier Harmeling, J; Kouwenberg, Casimir A E; Bijlard, Eveline; Burger, Koert N J; Jager, Agnes; Mureau, Marc A M

    2015-09-01

    Adjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The current systematic review aims to investigate this effect. During October 2014, a systematic search for clinical studies was performed in six databases with keywords related to breast reconstruction and chemotherapy. Eligible studies met the following inclusion criteria: (1) research population consisted of women receiving therapeutic mastectomy, (2) comparison of IBR with mastectomy only groups, (3) TTC was clearly presented and mentioned as outcome measure, and (4) original studies only (e.g., cohort study, randomized controlled trial, case-control). Fourteen studies were included, representing 5270 patients who had received adjuvant chemotherapy, of whom 1942 had undergone IBR and 3328 mastectomy only. One study found a significantly shorter mean TTC of 12.6 days after IBR, four studies found a significant delay after IBR averaging 6.6-16.8 days, seven studies found no significant difference in TTC between IBR and mastectomy only, and two studies did not perform statistical analyses for comparison. In studies that measured TTC from surgery, mean TTC varied from 29 to 61 days for IBR and from 21 to 60 days for mastectomy only. This systematic review of the current literature showed that IBR does not necessarily delay the start of adjuvant chemotherapy to a clinically relevant extent, suggesting that in general IBR is a valid option for non-metastatic breast cancer patients. PMID:26285643

  1. Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery?

    PubMed Central

    Niu, Hai-Fei; Wei, Li-Juan; Yu, Jin-Pu; Lian, Zhen; Zhao, Jing; Wu, Zi-Zheng; Liu, Jun-Tian

    2016-01-01

    Objective: Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. Methods: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). Results: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. Results indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67

  2. Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy

    PubMed Central

    2012-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) carcinomas rarely occur in the gallbladder. Here we reported a case of giant gallbladder unresectable mass with local liver invasion and omentum metastasis, which proved to be neuroendocrine carcinoma (NEC) by biopsy, received successful radical operation after neo-adjuvant chemotherapy plus somatostatin treatment. The patient showed good response as the neoplasm diminished dramatically and showed clear margin after 6 courses of treatment. A radical operation including cholecystectomy, hepatic wedge resection of the gallbladder fossa segment and lymph node of group 8a and 8p resection was performed successfully. Postoperative histopathological examination revealed neuroendocrine carcinoma mixed with adenocarcinoma in the gallbladder wall. Followed up showed no evidence of recurrence after 7 months of the operation. We suggest that neo-adjuvant chemotherapy may be beneficial to gallbladder mixed neuroendocrine carcinomas in an advanced stage which could also be advantageous to NEC of other organs. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2731892837743787 PMID:23186166

  3. Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis

    PubMed Central

    Brandi, Giovanni; De Lorenzo, Stefania; Nannini, Margherita; Curti, Stefania; Ottone, Marta; Dall’Olio, Filippo Gustavo; Barbera, Maria Aurelia; Pantaleo, Maria Abbondanza; Biasco, Guido

    2016-01-01

    Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials. PMID:26811604

  4. Recurrent Pericarditis, an Unexpected Effect of Adjuvant Interferon Chemotherapy for Malignant Melanoma

    PubMed Central

    Marmoush, Fady; Shafi, Muhammad Ismail; Shah, Ashish

    2016-01-01

    Drug-induced pericarditis is a well-described cardiac pathology that can result from a variety of medications; however, interferon-mediated pericarditis is extremely rare. We present a case of a young female with recurrent pericarditis due to interferon therapy. The role of interferon in adjuvant chemotherapy is well known and yields good effect, but this case highlights the very uncommon phenomena of interferon induced pericarditis and the significant distress it can cause. PMID:27418981

  5. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: A sequential approach

    SciTech Connect

    Lupe, Krystine; Kwon, Janice . E-mail: Janice.kwon@lhsc.on.ca; D'Souza, David; Gawlik, Christine; Stitt, Larry; Whiston, Frances; Nascu, Patricia; Wong, Eugene; Carey, Mark S.

    2007-01-01

    Purpose: To determine the feasibility of adjuvant paclitaxel and carboplatin chemotherapy interposed with involved field radiotherapy for women with advanced endometrial cancer. Methods and Materials: This was a prospective cohort study of women with Stage III and IV endometrial cancer. Adjuvant therapy consisted of 4 cycles of paclitaxel (175 mg/m{sup 2}) and carboplatin (350 mg/m{sup 2}) every 3 weeks, followed sequentially by external beam radiotherapy (RT) to the pelvis (45 Gy), followed by an additional two cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy (BT) were added at the discretion of the treating physician. Results: Thirty-three patients (median age, 63 years) received treatment between April 2002 and June 2005. Median follow-up was 21 months. Stage distribution was as follows: IIIA (21%), IIIC (70%), IVB (9%). Combination chemotherapy was successfully administered to 30 patients (91%) and 25 patients (76%), before and after RT respectively. Nine patients (27%) experienced acute Grade 3 or 4 chemotherapy toxicities. All patients completed pelvic RT; 19 (58%) received standard 4-field RT and 14 (42%) received intensity-modulated radiotherapy. Ten (30%) received extended field radiation. Four patients (12%) experienced acute Grade 3 or 4 RT toxicities. Six (18%) patients developed chronic RT toxicity. There were no treatment-related deaths. Two-year disease-free and overall survival rates were both 55%. There was only one pelvic relapse (3%). Conclusions: Adjuvant treatment with combination chemotherapy interposed with involved field radiation in advanced endometrial cancer was well tolerated. This protocol may be suitable for further evaluation in a clinical trial.

  6. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer - Drug Selection, Tolerability, and Safety in Clinical Practice].

    PubMed

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network(NCCN)guidelines, oxaliplatin(L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin(LV), and L-OHP(FOLFOX); capecitabine and L-OHP(CapeOX); , and 5-fluorouracil, folinic acid, and L-OHP(FLOX)are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur- uraci(l UFT)plus LV(UFT/LV)in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82(80%)received adjuvant chemotherapy and 21(20%)did not. CapeOX was administered to 32 patients(31%), UFT/LV to 49 patients(48%), and capecitabine to 1 patient(1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patient(s 54%)selected CapeOX, 26(44%)selected UFT/LV, and 1(2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition. PMID:27210088

  7. Helicobacter pylori and gastrointestinal symptoms in diagnostics and adjuvant chemotherapy of colorectal cancer.

    PubMed

    Soveri, Leena-Maija; Osterlund, Pia; Ruotsalainen, Tarja; Poussa, Tuija; Rautelin, Hilpi; Bono, Petri

    2014-02-01

    5-Fluorouracil (5-FU)-based chemotherapy is the mainstay of adjuvant treatment for colorectal cancer (CRC). Few studies have explored Helicobacter pylori (H. pylori)-associated gastrointestinal symptoms in the diagnosis of CRC, and the association between H. pylori infection and gastrointestinal toxicity during adjuvant chemotherapy in CRC. Seventy-nine CRC patients were randomised in a prospective clinical trial to receive 5-FU and leucovorin administered as bolus injection (Mayo regimen) or continuous infusion (simplified de Gramont regimen). H. pylori antibodies were analysed at baseline, twice monthly during treatment and after treatment up to 12 months. Thirty-seven patients (47%) were H. pylori-seronegative at baseline. There was no significant association between baseline H. pylori seropositivity (n=42; 53%) and oro-gastrointestinal toxicity during chemotherapy. The median time from symptom onset of CRC to surgery was significantly longer in patients with H. pylori infection (median time, 6 vs. 5 months; P=0.012). Functional dyspeptic symptoms at presentation significantly delayed diagnosis (median time, 7.5 vs. 5 months; P=0.035), whereas anaemia, bowel symptoms, occlusion, blood in the stool, infection and hypolactasia did not. We conclude that there is no association between H. pylori status and gastrointestinal toxicity in CRC patients during chemotherapy. Dyspeptic symptoms and presence of H. pylori may delay the diagnosis of CRC. (www.controlled-trials.com/ISRCTN98405441). PMID:24396486

  8. How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey

    PubMed Central

    Acevedo, Francisco; Sanchez, Cesar; Jans, Jaime; Rivera, Solange; Camus, Mauricio; Besa, Pelayo

    2014-01-01

    Background: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the Hispanic or Latino populations. Methods: We interviewed females with BC who had previously received adjuvant chemotherapy. Age, stage at presentation, time since last chemotherapy, type of chemotherapy, marital status, number of children, and level of education were recorded. We used the graphic representation from Adjuvant! Online to question each patient on how much survival benefit she required to accept chemotherapy. Results: There were 101 women surveyed. The average age was 55.9 (±10.2), 54.5% had involved lymph nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females accepted chemotherapy for an absolute survival benefit of 1% or less. In a multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018) were associated with lower survival benefit required to opt for chemotherapy. Conclusion: In our study, the acceptance of chemotherapy by the Hispanic population requires minimal survival benefit and is in agreement with the Caucasian population reported elsewhere. To our knowledge, our report is the first study that evaluates the perception of Latino patients regarding the benefit of chemotherapy in early BC. PMID:24678346

  9. Long-term outcome of adjuvant chemotherapy cyclophosphamide, mitoxantrone, and fluorouracil in women with breast cancer.

    PubMed

    Kumpulainen, Eero J; Hirvikoski, Pasi P; Johansson, Risto T

    2008-01-01

    The aim of the study is to report the long-term outcome and secondary tumours of early breast cancer patients of adjuvant CNF (cyclophosphamide, mitoxantrone, and 5-fluorouracil) chemotherapy. One hundred and ninety four patients, 185 primary early breast cancer and nine locoregionally recurrent breast cancer patients, were entered onto the trial between May 1986 and November 1993. The therapies included surgery, radiation therapy, adjuvant CNF chemotherapy, and tamoxifen according to hormonal status. Some of patients were treated twice with CMF (methotrexate). The median follow-up time was 12.9 years. Eighty nine (48%) primary breast cancers relapsed, and six locoregional breast cancers relapsed. After 5-10 years the relapse incidence decreased notably. Eighty three patients died of breast cancer, and nine of other causes. Two cases of leukemia, six cases of skin cancer, two cases of Hodgkin's disease, two cases of meningioma, and two cases of endometrial cancer were observed. This article confirms the feasibility of adjuvant CNF for early breast cancer patients. Questions of possible causability of secondary cancer have yet to be explored. PMID:18097780

  10. Surgery and Adjuvant Chemotherapy Use Among Veterans With Colon Cancer: Insights From a California Study

    PubMed Central

    Hynes, Denise M.; Tarlov, Elizabeth; Durazo-Arvizu, Ramon; Perrin, Ruth; Zhang, Qiuying; Weichle, Thomas; Ferreira, M. Rosario; Lee, Todd; Benson, Al B.; Bhoopalam, Nirmala; Bennett, Charles L.

    2010-01-01

    Purpose US veterans have been shown to be a vulnerable population with high cancer rates, and cancer care quality in Veterans Affairs (VA) hospitals is the focus of a congressionally mandated review. We examined rates of surgery and chemotherapy use among veterans with colon cancer at VA and non-VA facilities in California to gain insight into factors associated with quality of cancer care. Methods A retrospective cohort of incident colon cancer patients from the California Cancer Registry, who were ≥ 66 years old and eligible to use VA and Medicare between 1999 and 2001, were observed for 6 months after diagnosis. Results Among 601 veterans with colon cancer, 72% were initially diagnosed and treated in non-VA facilities. Among veterans with stage I to III cancer, those diagnosed and initially treated in VA facilities experienced similar colectomy rates as those at non-VA facilities. Stage III patients diagnosed and initially treated in VA versus non-VA facilities had similar odds of receiving adjuvant chemotherapy. In both settings, older patients had lower odds of receiving chemotherapy than their younger counterparts even when race and comorbidity were considered (age 76 to 85 years: odds ratio [OR] = 0.18; 95% CI, 0.07 to 0.46; age ≥ 86 years: OR = 0.17; 95% CI, 0.04 to 0.73). Conclusion In California, older veterans with colon cancer used both VA and non-VA facilities for cancer treatment, and odds of receiving cancer-directed surgery and chemotherapy were similar in both systems. Among stage III patients, older age lowered odds of receiving adjuvant chemotherapy in both systems. Further studies should continue to explore potential health system effects on quality of colon cancer care across the United States. PMID:20406940

  11. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

    PubMed Central

    Findlay, John M.; Castro-Giner, Francesc; Makino, Seiko; Rayner, Emily; Kartsonaki, Christiana; Cross, William; Kovac, Michal; Ulahannan, Danny; Palles, Claire; Gillies, Richard S.; MacGregor, Thomas P.; Church, David; Maynard, Nicholas D.; Buffa, Francesca; Cazier, Jean-Baptiste; Graham, Trevor A.; Wang, Lai-Mun; Sharma, Ricky A.; Middleton, Mark; Tomlinson, Ian

    2016-01-01

    How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful. PMID:27045317

  12. [A Case of Nasopharyngeal Cancer with Febrile Neutropenia Followed by Death during Adjuvant Chemotherapy].

    PubMed

    Nakahara, Susumu; Kitamura, Koji; Honma, Keiichiro; Yamamoto, Yoshifumi; Takenaka, Yukinori; Yasui, Toshimichi; Hanamoto, Atsushi; Morii, Eiichi; Inohara, Hidenori

    2015-06-01

    Chemotherapy-related death can occur, but is rarely experienced in the case of head and neck cancer. In this report, we present the case of a 55-year-old male who died of a severe febrile neutropenia during adjuvant chemotherapy. He was initially diagnosed as having nasopharyngeal carcinoma (cT2N0M0), and concurrent chemoradiotherapy was used as a primary treatment. He did not show any critical side effects during that therapy. After residual disease was proven by biopsy, docetaxel, cisplatin and 5-fluorouracil (TPF) therapy was introduced as adjuvant chemotherapy. The patient developed a high fever with a decreased neutrophil count on day 8, and went into a state of shock on day 9. He underwent immediate systemic management, but methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and enteritis were uncontrolled, resulting in death on day 43. The autopsy findings suggested that the main cause of death was acute respiratory distress syndrome (ARDS), but cytomegalovirus (CMV) infection was also noted in multiple organs. . Since it is assumed from literature that the mortality rate in TPF therapy is about 2-4%, it was considered that prior sufficient explanations and informed consent should be required before this therapy. PMID:26336750

  13. [Surgical resection with adjuvant chemotherapy for locally advanced Masaoka stage IVa thymoma; report of a case].

    PubMed

    Takeshige, Mariko; Aoki, Tadashi; Motono, Nozomu; Shimada, Koji; Nakayama, Takashi; Yazawa, Masatomo

    2010-03-01

    A 39-year-old woman was presented with a mediastinal tumor and some pleural tumors. A computed tomography (CT)-guided needle biopsy of the pleural tumor was undertaken which showed thymoma, type B1 according to the World Health Organization classification. She had underwent extended-thymectomy and resection of all pleural tumors. Histopathology confirmed these lesions to be type B2 thymoma and pleural dissemination. She received adjuvant chemotherapy. Two years after surgery the patient is alive without recurrence. PMID:20214360

  14. [A Case of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

    PubMed

    Inoue, Katsuki; Shimada, Makoto; Saito, Katsuyuki; Ogawa, Yuuichiro; Matsubara, Eiji; Matsumoto, Yuuki; Keiichiro, Hayashi

    2015-11-01

    A 49-year-old female presented complaining of gross hematuria. Cystoscopy and magnetic resonance imaging revealed a papillary tumor on the bladder dome. At biopsy pathology the tumor was diagnosed as adenocarcinoma. We diagnosed the tumor as urachal adenocarcinoma and performed partial cystectomy of bladder dome with en-bloc resection of the urachal ligament up to the umbilicus. In surgical pathology, the tumor had invaded to the fat tissue around the urachal ligament with metastasis to the lymph node. Therefore the tumor was diagnosed as a stage IVA (Sheldon's category) urachal adenocarcinoma. After surgery, 6 cycles of chemotherapy with TS-1 and cisplatin (CDDP) were performed. There has been no relapse 5 years after surgery. This is the first report of successful adjuvant chemotherapy with TS-1/CDDP for advanced urachal adenocarcinoma. PMID:26699888

  15. Should all patients with serous and clear cell endometrial carcinoma receive adjuvant chemotherapy?

    PubMed

    Boren, Todd P; Miller, David S

    2010-11-01

    Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC. PMID:21118038

  16. In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

    PubMed Central

    Kwon, Hye Youn; Kim, Im-kyung; Kang, Jeonghyun; Sohn, Seung-Kook; Lee, Kang Young

    2016-01-01

    Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy. PMID:26511802

  17. GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

    PubMed Central

    Lin, Wey-Ran; Chiang, Jy-Ming; Liang, Kung-Hao; Lim, Siew-Na; Lai, Ming-Wei; Tsou, Yung-Kuan; Hsieh, Tzu-Yun; Hsu, Chih-Kai; Yeh, Chau-Ting

    2016-01-01

    Abstract Adjuvant oxaliplatin-based chemotherapy is widely used for stage III colorectal cancer (CRC) after curative surgery. CRC is a molecularly heterogeneous disease, and our current knowledge of therapeutic response-related genetic factors remains limited. N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype is a prognostic predictor for chemotherapy response in advanced hepatocellular carcinoma. Here, we investigated whether this genotype was related to the therapeutic outcome of stage III CRC. A cohort of 300 stage III CRC patients receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited. GALNT14 genotypes and the clinicopathological factors were correlated with posttherapeutic prognosis. Of these patients, 18% patients had GALNT14-rs9679162 “TT” and 82% had the “GT” + “GG” genotypes. The analysis showed that the “TT” genotype was associated with unfavorable overall survival (OS, P = 0.009) but not with recurrence-free survival (RFS, P = 0.700). The subgroup analysis showed that the “TT” genotype was associated with unfavorable OS in the following subgroups: age ≤65 years, men, left side CRC, N2 stage, carcinoembryonic antigen >5 ng/mL, and mucinous histology (P = 0.012, 0.011, 0.009, 0.025, 0.013, and 0.007, respectively). Within the latter 2 subgroups, the “TT” genotype was the only independent predictor for OS. Finally, the “TT” genotype was associated with the T4 tumor stage (P = 0.017) and in patients with T4 tumors, the “TT” genotype was the only independent predictor for unfavorable RFS (P = 0.007). GALNT14 “TT” genotype was associated with unfavorable OS in stage III CRC patients receiving curative surgery and adjuvant oxaliplatin-based chemotherapy. PMID:27124048

  18. [Adjuvant chemotherapy].

    PubMed

    Del Nero, A; Mandressi, A; Longo, G; Cogni, M; Mangiarotti, B; Buzzetti, V; Russo, R

    1991-06-01

    The authors treated 10 advanced renal cell carcinoma with circadian venous continuous infusion of 5-Fluoro 2-Deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump in 14-day cycles alternating with 14-day intervals of physiologic saline infusion. Of the patient observed for at least 8 months (range: 8-32, median: 22.1) 1 showed progression. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is administrated in on entirely out patient setting, and associated with a normal quality of life. PMID:1830673

  19. [Integrative management of operation, perioperative rehabilitation and postoperative adjuvant chemotherapy in elderly patients with colorectal carcinoma].

    PubMed

    Xu, Dong; Jiao, Yurong; Ding, Kefeng

    2016-05-25

    With the aging of the Chinese population, it seems obvious that the number of elderly patients with the disease of colorectal carcinoma grows significantly. Meanwhile, no evidence-based practical guideline for the treatment of colorectal carcinoma are available in this particular age group. Therefore, the concept of integrative management has been brought up by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University, which combines the processes of surgery, perioperative rehabilitation and adjuvant chemotherapy together. In this way, the cooperation and complementarity between different clinical departments could cooperate and complete tasks together to integrate the treatment processes into a cohesive one. To achieve the goal of integrative management, the project is divided into horizontal and vertical aspects. The horizontal integration means the cooperation between different clinical departments, which is also known as multi-discipline treatment (MDT). The vertical integration reflects the completeness of the entire treatment under the goal of consistency, strictness and job separation, which could also be explained as the clinical pathway. Furthermore, this review stresses on the integrative strategy of both clinical and biochemical indexes rehabilitation, as well as the operation and postoperative adjuvant chemotherapy which has been put in execution several years by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University. PMID:27215515

  20. The Nature and Severity of Cognitive Impairment Associated with Adjuvant Chemotherapy in Women with Breast Cancer: A Meta-Analysis of the Current Literature

    ERIC Educational Resources Information Center

    Falleti, Marina G.; Sanfilippo, Antonietta; Maruff, Paul; Weih, LeAnn; Phillips, Kelly-Anne

    2005-01-01

    Objective: Several studies have identified that adjuvant chemotherapy for breast cancer is associated with cognitive impairment; however, the magnitude of this impairment is unclear. This study assessed the severity and nature of cognitive impairment associated with adjuvant chemotherapy by conducting a meta-analysis of the published literature to…

  1. Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy.

    PubMed

    Vacchelli, Erika; Enot, David P; Pietrocola, Federico; Zitvogel, Laurence; Kroemer, Guido

    2016-06-01

    Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense double-stranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. Cancer Res; 76(11); 3122-6. ©2016 AACR. PMID:27197163

  2. Economic Evaluation of First-Line Adjuvant Chemotherapies for Resectable Gastric Cancer Patients in China

    PubMed Central

    Tan, Chongqing; Peng, Liubao; Zeng, Xiaohui; Li, Jianhe; Wan, Xiaomin; Chen, Gannong; Yi, Lidan; Luo, Xia; Zhao, Ziying

    2013-01-01

    Background First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. Objective The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. Methods A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. Results For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. Conclusions Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a

  3. Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy

    SciTech Connect

    Lippman, M.E.; Edwards, B.K.; Findlay, P.; Danforth, D.W. Jr.; MacDonald, H.; D'Angelo, T.; Gorrell, C.

    1986-01-01

    Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.

  4. Is distance to chemotherapy an obstacle to adjuvant care among the N.C. Medicaid—enrolled colon cancer patients?

    PubMed Central

    Song, Eunyoung; Klepin, Heidi D.; Foley, Kristie L.

    2016-01-01

    Background Adjuvant chemotherapy for colon cancer has been linked to patient and provider characteristics but little is known about whether distance to chemotherapy providers constitutes an obstacle to chemotherapy. Methods A total of 1,184 Medicaid patients diagnosed with colon cancer in North Carolina in 1999–2002 comprised the sample. Data from the N.C. Central Cancer Registry, N.C. Medicaid Claims, American Hospital Directory and US Census were merged. Logistic regression models were used to estimate the association between chemotherapy receipt and the distance to nearest chemotherapy provider. Results Compared to the referent group of SEER-staged II (local) cancer patients living less than 2 miles from the nearest chemotherapy provider, the odds of receiving chemotherapy fell as the distance to the nearest provider increased. The odds ratio (OR) for those living ≥5 to <15 miles away was 0.13 [95% confidence intervals (CI), 0.04–0.39], and OR for those living ≥15 miles away was 0.06 (95% CI, 0.01–0.52). Patients diagnosed with regional, SEER-staged III (regional) cancer were less likely to receive chemotherapy if they lived in rural areas more than 20 miles away from the nearest provider (OR =0.08; 95% CI, 0.01–0.72). However, we found no evidence of association between chemotherapy receipt and distance to the nearest provider for regional cancer patients living in urban areas and those living in rural areas within 20 miles from the nearest chemotherapy provider. Conclusions Distance to provider may be an obstacle to chemotherapy for some groups of low-income colon cancer patients. Relieving travel burdens of rural patients living far from providers may help Medicaid increase guideline-consistent adjuvant care for regional cancer patients. PMID:27284464

  5. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

    PubMed Central

    Zhang, Yi; Tolani, Bhairavi; Mo, Minli; Zhang, Hua; Zheng, Qingfeng; Yang, Yue; Cheng, Runfen; Jin, Joy Q.; Luh, Thomas W.; Yang, Cathryn; Tseng, Hsin-Hui K.; Giroux-Leprieur, Etienne; Woodard, Gavitt A.; Hao, Xishan; Wang, Changli; Jablons, David M.; He, Biao

    2015-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID:26132438

  6. Cardiac Monitoring During Adjuvant Trastuzumab-Based Chemotherapy Among Older Patients With Breast Cancer

    PubMed Central

    Chavez-MacGregor, Mariana; Niu, Jiangong; Zhang, Ning; Elting, Linda S.; Smith, Benjamin D.; Banchs, Jose; Hortobagyi, Gabriel N.; Giordano, Sharon H.

    2015-01-01

    Purpose Patients treated with adjuvant trastuzumab require adequate cardiac monitoring. We describe the patterns of cardiac monitoring and evaluate factors associated with adequate monitoring in a large population-based study of older patients with breast cancer. Patients and Methods Patients age 66 years or older with full Medicare coverage, diagnosed with stage I to III breast cancer between 2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases. The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use, cardiac monitoring, and comorbidities were identified by using International Classification of Diseases, 9th revision and Healthcare Common Procedure Coding System codes. Prescribing physician characteristics were also evaluated. Analyses included descriptive statistics and multilevel logistic regression models. Results In all, 2,203 patients were identified; median age was 72 years. Adequate monitoring was identified in only 36.0% of the patients (n = 793). In the multivariable model, factors associated with optimal cardiac monitoring included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990 (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a determinant for cardiac monitoring. Of the variance in the adequacy of cardiac monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors. Conclusion A large proportion of patients had suboptimal cardiac monitoring. Physician characteristics had more influence than measured patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed

  7. Adjuvant chemotherapy after primary treatments for cervical cancer: a critical point of view and review of the literature.

    PubMed

    Angioli, Roberto; Luvero, Daniela; Aloisi, Alessia; Capriglione, Stella; Gennari, Paolo; Linciano, Francesca; Li Destri, Marta; Scaletta, Giuseppe; Montera, Roberto; Plotti, Francesco

    2014-04-01

    Cervical cancer is the second most frequent female malignancy worldwide. Concurrent chemoradiotherapy represents the standard of care for patients with advanced stage cervical cancer, while radical surgery (RS) and radiotherapy is widely used for treating early stage cervical cancer. However, the poor control of micrometastasis, declining operability, the lack of radiotherapy departments and the high incidence of long-term complications due to radiotherapy have brought about the development of different therapeutic approaches such as neoadjuvant chemotherapy followed by RS. Unfortunately, treatment results are still unsatisfactory due to a high recurrence rate and several authors have studied the possibility to add an adjuvant treatment to primary therapy. We reviewed the literature concerning the role of adjuvant chemotherapy in advanced cervical cancer after neoadjuvant chemotherapy followed by RS and after chemoradiotherapy. PMID:24483847

  8. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  9. Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial

    PubMed Central

    Brodowicz, Thomas; Schwameis, Eva; Widder, Joachim; Amann, Gabriele; Wiltschke, Christoph; Dominkus, Martin; Windhager, Reinhard; Ritschl, Peter; Pötter, Richard; Kotz, Rainer

    2000-01-01

    Purpose. The present prospective randomized adjuvant trial was carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade 2 and grade 3 soft tissue sarcoma (STS). Patients and methods. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or under the addition of six courses of ifosfamide (1500 mg/m2 , days 1–4), dacarbazine (DTIC) (200 mg/m2 , days 1–4) and doxorubicin (25 mg/m2 , days 1–2) administered in 14-day-intervals supported by granulocyte-colony stimulating factor (30 × 106 IU/day, s.c.) on days 5–13. According to the randomization protocol, 28 patients received radiotherapy only, whereas 31 patients were treated with additional chemotherapy. Results. The relative ifosfamide–doxorubicin–DTIC (IFADIC) dose intensity achieved was 93%. After a mean observation period of 41±19.7 months (range, 8.1–84 months), 16 patients (57%) in the control group versus 24 patients (77%) in the chemotherapy group were free of disease (p>0.05).Within the control group, tumor relapses occurred in 12 patients (43%;six patients with distant metastases, two with local relapse, four with both) versus seven patients (23%; five patients with distant metastases, one with local recurrence, one with both) from the chemotherapy group. Relapse-free survival (RFS) (p=0.1), time to local failure (TLF) (p=0.09), time to distant failure (TDF) (p=0.17) as well as overall survival (OS) (p=0.4) did not differ significantly between the two treatment groups. Treatment-related toxicity was generally mild in both treatment arms. Conclusion. We conclude that the safety profile of intensified IFADIC added to radiotherapy was manageable and tolerable in the current setting. Inclusion of intensified IFADIC was not translated into a significant benefit concerning OS, RFS, TLF and

  10. Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

    PubMed Central

    Oostra, Drew R.; Lustberg, Maryam B.; Reinbolt, Raquel E.; Pan, Xueliang; Wesolowski, Robert; Shapiro, Charles L.

    2015-01-01

    Purpose Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. Methods Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea. Results Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm2 to 0.976 g/cm2 and 0.937 g/cm2 at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). Conclusions In what was likely a compensatory response to rapid bone loss, CIOF patients’ OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF. PMID:25575458

  11. Identification of distinct fatigue trajectories in patients with breast cancer undergoing adjuvant chemotherapy

    PubMed Central

    Junghaenel, Doerte U.; Cohen, Jules; Schneider, Stefan; Neerukonda, Anu R.; Broderick, Joan E.

    2015-01-01

    Purpose The goal of this study was to characterize changes in daily fatigue in women undergoing chemotherapy for breast cancer. We examined whether there are subgroups of patients with distinct fatigue trajectories and explored potential psychosocial and biomedical predictors of these subgroups. Methods Participants were 77 women with breast cancer receiving adjuvant chemotherapy with AC-T (2-week cycle) and TC or TCH (3-week cycle) regimens. They completed 28 daily ratings online using an adapted version of the Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue instrument. Results Both regimens followed an “inverted-U shaped” fatigue pattern over approximately 2 weeks. Growth mixture modeling identified three patient subgroups with distinct trajectories. Fatigue scores in the “low fatigue” group (23%) increased following the infusion and quickly abated. The “transient fatigue” (27%) group had a very pronounced increase. Patients in the “high fatigue” (50%) group reported consistently elevated fatigue with a relatively small increase. Demographic and medical variables were not associated with fatigue trajectory. Patients in the “high fatigue” group reported significantly poorer physical, emotional, and social functioning, poorer general health, and more depressed mood than patients in the “low fatigue” group. The “transient fatigue” group reported significantly better physical and social functioning than the “high fatigue” group, but emotional distress and depression similar to the “high fatigue” group. Conclusions The identification of patient subgroups with distinct fatigue trajectories during chemotherapy is an essential step for developing preventative strategies and tailored interventions. Our results suggest that different trajectories are associated with patients’ psychosocial and general health. PMID:25876159

  12. Adjuvant therapy for highly malignant canine mammary tumours: Cox-2 inhibitor versus chemotherapy: a case-control prospective study.

    PubMed

    Arenas, C; Peña, L; Granados-Soler, J L; Pérez-Alenza, M D

    2016-07-30

    Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases. PMID:27377395

  13. Biological characterization and selection criteria of adjuvant chemotherapy for early breast cancer: experience from the Italian observational NEMESI study

    PubMed Central

    2012-01-01

    Background International treatment guidelines recommend administration of adjuvant chemotherapy in early breast cancer based on clinical, prognostic and predictive parameters. Methods An observational study (NEMESI) was conducted in 63 Italian oncology centres in patients with early breast cancer. Age, performance status, concomitant disease, menopausal status, histology, tumor dimension (pT), axillary lymph node status (pN), grading (G), estrogen and progesterone receptor (ER and PgR), proliferative index (ki67 or MIB-1), human epidermal growth factor receptor 2 (HER2) and type of adjuvant treatment were recorded. The primary objective of the study was to define parameters influencing the decision to prescribe adjuvant chemotherapy and the type of chemotherapy. Results Data for 1894 patients were available. 69.0% postmenopausal, 67.0% pT1, 22.3% pTmic/pT1a/pT1b, 61.0% pN0, 48.7% luminal A, 18.1% luminal B, 16.1% HER2 positive, 8.7% triple negative, 8.4% unknown. 57.8% received adjuvant chemotherapy: 38.1% of luminal A, 67.3% luminal B, 88.2% HER2-positive, 97.6% triple negative. Regimens administered: 9.1% CMF-like, 48.8% anthracyclines, 38.4% anthracyclines plus taxanes, 3.7% taxanes alone. Increasing pT/pN and, marginally, HER2-positive were associated with the prescription of anthracyclines plus taxanes. Suboptimal schedules (CMF-like or AC/EC or FEC-75) were prescribed in 37.3% receiving chemotherapy, even in HER2-positive and triple negative disease (36.5% and 34.0%, respectively). Conclusions This study showed an overprescription of adjuvant chemotherapy for early breast cancer, particularly referred to luminal A. pT, pN and, marginally, HER2 were the principal determinants for the choice of chemotherapy type. Suboptimal chemotherapy regimens were adopted in at least one third of HER2-positve and triple negative. PMID:22672524

  14. Single Nucleotide Polymorphisms as Prognostic and Predictive Factors of Adjuvant Chemotherapy in Colorectal Cancer of Stages I and II

    PubMed Central

    Horvat, Matej; Potočnik, Uroš; Repnik, Katja; Kavalar, Rajko; Štabuc, Borut

    2016-01-01

    Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant. PMID:26884752

  15. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT

    PubMed Central

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-01-01

    Nasopharyngeal carcinoma (NPC) patients with N2–3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2–3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194–0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187–0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  16. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    PubMed

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  17. Cost-effectiveness of adjuvant FOLFOX and 5FU/LV chemotherapy for patients with stage II colon cancer

    PubMed Central

    Ayvaci, Mehmet U.S.; Shi, Jinghua; Alagoz, Oguzhan; Lubner, Sam

    2014-01-01

    Purpose We evaluated the cost-effectiveness of adjuvant chemotherapy using 5-fluorouracil, leucovorin (5FU/LV), and oxaliplatin (FOLFOX) compared with 5FU/LV alone and 5FU/LV compared with observation alone for patients who had resected stage II colon cancer. Methods We developed two Markov models to represent the adjuvant chemotherapy and follow-up periods and a single Markov model to represent the observation group. We used calibration to estimate the transition probabilities among different toxicity levels. The base-case considered 60-year-old patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer and was medically fit to receive 6 months of adjuvant chemotherapy. We measured health outcomes in quality-adjusted life-years (QALYs) and estimated costs using 2007 US$. Results In the base-case, adjuvant chemotherapy of FOLFOX regimen had an incremental cost-effectiveness ratio (ICER) of $54,359/QALY compared with the 5FU/LV regimen and the 5FU/LV regimen had an ICER of $14,584/QALY compared with the observation group from the third-party payer perspective. The ICER values were most sensitive to 5-year relapse probability, cost of adjuvant chemotherapy, and the discount rate for the FOLFOX arm, whereas the ICER value of 5FU/LV was most sensitive to the 5-year relapse probability, 5-year survival probability, and the relapse cost. The probabilistic sensitivity analysis indicate that the ICER of 5FU/LV is less than $50,000/QALY with a probability of 99.62% and the ICER of FOLFOX as compared to 5FU/LV is less than $50,000/QALY and $100,000/QALY with a probability of 44.48% and 97.24%, respectively. Conclusion While adjuvant chemotherapy with 5FU/LV is cost-effective at all ages for patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer, FOLFOX is not likely to be cost-effective as compared to 5FU/LV. PMID:23313932

  18. Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

    SciTech Connect

    Schoenfeld, Jonathan D.; Sher, David J.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Balboni, Tracy A.; Tishler, Roy B.

    2012-01-01

    Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of

  19. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    SciTech Connect

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.; and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  20. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    SciTech Connect

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  1. Predominant histologic subtype in lung adenocarcinoma predicts benefit from adjuvant chemotherapy in completely resected patients: discovery of a holy grail?

    PubMed

    Russell, Prudence Anne; Wright, Gavin Michael

    2016-01-01

    The recently published 2015 World Health Organisation (WHO) classification of lung tumors, which is based on the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ATS) multidisciplinary classification, recommends diagnosis of resected lung adenocarcinoma according to the predominant histologic subtype. This has been shown to correlate with overall and disease-free survival (DFS) in many studies from four continents. Now classification according to predominant histologic subtype has been demonstrated to predict benefit from adjuvant chemotherapy in a subset of patients with completely resected lung adenocarcinoma previously included in the International Adjuvant Lung Cancer Trial (IALT), JBR.10, Cancer and Leukemia Group B (CALGB) 9633 and Adjuvant Navelbine International Trialist Association 01 (ANITA) adjuvant chemotherapy trials, all of which were part of the LACE-Bio study. This "hot-off-the press" landmark investigation further cements the clinical importance of classification of resected lung adenocarcinoma according to predominant histologic subtype and suggests that it could be a critical factor for patient stratification in future clinical trials. PMID:26855952

  2. Predominant histologic subtype in lung adenocarcinoma predicts benefit from adjuvant chemotherapy in completely resected patients: discovery of a holy grail?

    PubMed Central

    Wright, Gavin Michael

    2016-01-01

    The recently published 2015 World Health Organisation (WHO) classification of lung tumors, which is based on the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ATS) multidisciplinary classification, recommends diagnosis of resected lung adenocarcinoma according to the predominant histologic subtype. This has been shown to correlate with overall and disease-free survival (DFS) in many studies from four continents. Now classification according to predominant histologic subtype has been demonstrated to predict benefit from adjuvant chemotherapy in a subset of patients with completely resected lung adenocarcinoma previously included in the International Adjuvant Lung Cancer Trial (IALT), JBR.10, Cancer and Leukemia Group B (CALGB) 9633 and Adjuvant Navelbine International Trialist Association 01 (ANITA) adjuvant chemotherapy trials, all of which were part of the LACE-Bio study. This “hot-off-the press” landmark investigation further cements the clinical importance of classification of resected lung adenocarcinoma according to predominant histologic subtype and suggests that it could be a critical factor for patient stratification in future clinical trials. PMID:26855952

  3. Primary proximal epithelioid sarcoma of the lung successfully treated with pneumonectomy and adjuvant chemotherapy.

    PubMed

    Saha, Debjit; Basu, Arnab; Maiti, Abhishek; Rodriguez, Estelamari

    2016-01-01

    Primary sarcomas of the lung and proximal epithelial sarcomas (PESs) are extremely rare. Inactivation of INI1 has been found in the majority of epithelioid sarcoma (ES). We report the third known case of a primary PES of the lung along with immunohistochemical data. A 41-year-old man with HIV infection, on highly active antiretroviral therapy, presented with haemoptysis, shortness of breath and progressive weight loss for 2 months. He was eventually diagnosed with stage IIA cT2bN0M0 grade-2 primary PES of the lung. This patient underwent pneumonectomy and adjuvant chemotherapy with ifosfamide and doxorubicin. He remains in remission 36 months since diagnosis. Our case stands to help other clinicians as treatment of such rare cases is often reliant on case reports. We also posit a possible pathogenic mechanism given a history of HIV infection in this patient. The association of INI1 mutation with other atypical sarcomas in patients with HIV infection merits further evaluation. PMID:27045049

  4. BMI Influences Prognosis Following Surgery and Adjuvant Chemotherapy for Lymph Node Positive Breast Cancer

    PubMed Central

    Vitolins, Mara Z.; Kimmick, Gretchen G.; Case, L. Douglas

    2016-01-01

    Increased body mass index (BMI) at diagnosis has been shown to be associated with an increased risk of disease recurrence and death. However, the association has not been consistent in the literature and may depend on several factors such as menopausal status, extent of disease, and receptor status. We performed a secondary analysis on what we believe is the largest prospective trial of adjuvant chemotherapy to assess the effect of BMI on prognosis in women with lymph node positive breast cancer. The study included 636 women with a median follow-up of over 13 years. Cox’s proportional hazards regression model was used to assess the effect of BMI on outcomes. Kaplan–Meier methods were used to estimate survival curves and log rank tests were used to assess differences in survival for BMI groups. We found that increased BMI was generally predictive of faster time to recurrence and decreased survival, but that the relationship was stronger for younger women, those with progesterone receptor negative disease and those with a greater number of lymph nodes that were positive. PMID:18540954

  5. [Adjuvant chemotherapy for breast cancer and fertility: estimation of the impact, options of preservation and role of the oncologist].

    PubMed

    Mailliez, Audrey; Decanter, Christine; Bonneterre, Jacques

    2011-07-01

    Fifty-two thousand new breast cancers occur each year in France, 7% in patients less than 40 years. The standard regimens of adjuvant chemotherapy for breast cancer now include anthracyclines and taxanes. These therapeutics advances have significantly improved the prognosis of these young women who may later wish to become mother and have biological offspring. The impact of chemotherapy on reproductive function should be accurately assessed and the ovarian reserve has to be taken into account. The estimated risk of chemo-induced amenorrhea and infertility has to be balanced with the expected results and risks of methods of fertility preservation. The place of different options for fertility preservation depends on patient age, presence or not of a partner and the time available before the initiation of treatment. For these breast cancer patients who will receive chemotherapy, new techniques of in vitro oocyte maturation seem promising. Even if some ethical and technical issues are unresolved, fertility preservation must now be part of the management of these young patients receiving adjuvant chemotherapy for breast cancer. This new approach must be multidisciplinary and complex. PMID:21700552

  6. Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials.

    PubMed Central

    Tierney, J. F.; Mosseri, V.; Stewart, L. A.; Souhami, R. L.; Parmar, M. K.

    1995-01-01

    Fifteen published randomised trials comparing adjuvant chemotherapy with no chemotherapy in soft-tissue sarcoma (STS) were identified (1546 patients). A qualitative review and a meta-analysis of this published literature were performed. With the qualitative review it was not possible to synthesise the apparently conflicting results of individual trials. The meta-analysis of the published data suggests an improvement in survival at 2 years (OR = 0.73, 95% CI = 0.53-0.99, P = 0.044) and at 5 years (OR = 0.59, 95% CI = 0.45-0.78, P = 0.0002) in favour of chemotherapy. However, the assumptions and approximations required to conduct this quantitative summary demand that the results are interpreted with caution. The only reliable means of assessing the current evidence on whether adjuvant chemotherapy has a role in the treatment of patients with STS, is to collect, check and reanalyse individual patients data (IPD) from each trial centrally, and formally combine the results in a stratified time-to-event analysis. Such an IPD analysis is currently being undertaken by an international collaborative group. PMID:7640234

  7. Vinflunine – an active chemotherapy for treatment of advanced non-small-cell lung cancer previously treated with a platinum-based regimen: results of a phase II study

    PubMed Central

    Bennouna, J; Breton, J-L; Tourani, J-M; Ottensmeier, C; O'Brien, M; Kosmidis, P; Huat, T E; Pinel, M-C; Colin, C; Douillard, J-Y

    2006-01-01

    A multicentre, single-arm, phase II trial designed to determine the efficacy of single-agent vinflunine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with a platinum-based regimen. The objectives were to assess efficacy in terms of tumour response rate (primary end point), duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients with advanced NSCLC with progressive disease having failed prior platinum-based first-line treatment for advanced disease. Five responses out of the 63 treated patients were documented by WHO criteria and validated by an independent panel review (IRP), yielding a response rate of 7.9% (95% CI: 2.6–17.6) in the intent-to-treat analysis and 8.3% (95% CI: 2.8–18.4) in the evaluable population. Disease control was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of response (complete response+partial response), according to modified WHO criteria was 7.8 months (95% CI: 4.6–NR). Median PFS was 2.6 months (95% CI: 1.4–3.8), and the median survival was 7.0 months (95% CI: 5.8–9.2). Grades 3–4 neutropenia was reported in 50% of patients; febrile neutropenia was observed in two patients (3.2%); grades 3–4 myalgia and grade 3 constipation were experienced by 10 (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable, noncumulative and could be prevented with laxative prophylaxis. The encouraging results from this phase II study with vinflunine warrant further investigations in phase III trials as second- or first-line treatment of advanced non-small-cell lung carcinoma, as a single agent or in combination with other active drugs. PMID:16641911

  8. Adjuvant chemotherapy of pT1a and pT1b breast carcinoma: results from the NEMESI study

    PubMed Central

    2012-01-01

    Background The prognosis of pT1a-pT1b breast cancer (BC) used to be considered very good, with a 10-y RFS of 90%. However, some retrospective studies reported a 10-y RFS of 81%–86% and suggested benefit from adjuvant systemic therapy. Methods To evaluate the variables that determined the choice of adjuvant chemotherapy and the type of chemotherapy delivered in pT1a-pT1b BC, we analysed the small tumours enrolled in the NEMESI study. Results Out of 1,894 patients with pathological stage I-II BC enrolled in NEMESI, 402 (21.2%) were pT1a-pT1b. Adjuvant chemotherapy was delivered in 127/402 (31.59%). Younger age, grading G3, high proliferative index, ER-negative and HER2-positive status were significantly associated with the decision to administer adjuvant chemotherapy. An anthracycline without taxane regimen was administered in 59.1% of patients, anthracycline with taxane in 24.4%, a CMF-like regimen in 14.2% and taxane in 2.4%. Adjuvant chemotherapy was administered in 88.4% triple-negative and 73.46% HER2-positive pT1a-pT1b BC. Adjuvant trastuzumab was delivered in 30/49 HER2-positive BC (61.2%). Conclusions Adjuvant chemotherapy was delivered in 31.59% T1a-pT1b BC treated at 63 Italian oncological centres from January 2008 to June 2008. The choice to deliver chemotherapy was based on biological prognostic factors. Anthracycline-based chemotherapy was administered in 83.5% patients. PMID:22545982

  9. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    SciTech Connect

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    2009-12-01

    Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m{sup 2} intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m{sup 2} intravenously on Days 1 and 8 or capecitabine 1500 mg/m{sup 2} orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m{sup 2} orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

  10. Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection

    PubMed Central

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja MJ; Beets-Tan, Regina GH; Beets, Geerard L

    2016-01-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorised into 3 groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). 1723(52%) of 3313 included patients received aCT. 898 patients had a pCR, 966 had a ypT1-2 tumour and 1302 had a ypT3-4 tumour. For 122 patients response category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. Hazard ratios for RFS with 95%CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. PMID:25418551

  11. The effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest, or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In the five men with normal testicular function, FSH was increased fourfold during therapy but returned to normal six to 21 months after treatment. In men less than 40 years old, the mean FSH was less than that of men over 40 years of age (P . to 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data increase in FSH, and reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  12. Effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In men less than 40 years old, the mean FSH level was less than that of men over 40 years of age (P = 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data indicate that reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  13. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

    PubMed

    Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

    2016-07-01

    With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests. PMID:27162322

  14. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    SciTech Connect

    Ogawa, Kazuhiko; Ito, Yoshinori; Hirokawa, Naoki; Shibuya, Keiko; Kokubo, Masaki; Ogo, Etsuyo; Shibuya, Hitoshi; Saito, Tsutomu; Onishi, Hiroshi; Karasawa, Katsuyuki; Nemoto, Kenji; Nishimura, Yasumasa

    2012-06-01

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  15. Effect of Active Hexose-Correlated Compound in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Retrospective Study

    PubMed Central

    Hangai, Sho; Iwase, Satoru; Kawaguchi, Takashi; Kogure, Yasunori; Matsunaga, Tadaharu; Nagumo, Yoshinori; Yamaguchi, Takuhiro

    2013-01-01

    Abstract Objectives Anthracyclines and taxanes are often used as first-line chemotherapy treatments in patients with breast cancer. There are, however, significant toxicity and side effects associated with these therapies. Previous studies have demonstrated that active hexose-correlated compound (AHCC) reduces such side effects. The present study explored the beneficial effects of AHCC on adverse events in patients receiving adjuvant chemotherapy for breast cancer. Subjects Forty-one women who were treated with anthracyclines and taxanes at Nagumo Clinic in Tokyo from October 2004 to March 2011 were selected for this study. Outcome measures We compared the occurrence of adverse events in patients who received AHCC with those who did not receive AHCC. Using Fisher's exact tests, we also compared the worst-grade adverse events in each treatment cycle. Generalized estimating equations were employed to compare longitudinal changes, and the use of granulocyte colony-stimulating factor, in the two groups was analyzed using Student's t-test. Results We found that, compared to the control group, the AHCC group had significantly fewer neutrophil-related events (odds ratio, 0.30; p=0.016), significantly lower use of granulocyte colony-stimulating factor, and a higher (although not significant) rate of adverse events associated with γ-glutamyl transpeptidase. Conclusions AHCC has the potential to reduce the severity of neutropenia induced by breast cancer chemotherapy and the use of G-CSF during chemotherapy. PMID:23829813

  16. A case of long-term 24-month survival in pancreatic anaplastic carcinoma (giant cell type) after S1 postoperative adjuvant chemotherapy

    PubMed Central

    Nitta, Toshikatsu; Fujii, Kensuke; Kataoka, Jun; Tominaga, Tomo; Kawasaki, Hiroshi; Ishibashi, Takashi

    2016-01-01

    We herein describe the case of a 70-year-old female patient diagnosed with pancreatic carcinoma. An abdominal enhanced computed tomography scan revealed a poorly enhanced mass (17 mm × 15 mm in size) in the pancreatic head. Magnetic resonance cholangiopancreatography revealed stenosis of the main pancreatic and common bile ducts caused by a mass-neighboring cyst. Based on these findings, we performed subtotal stomach-preserving pancreaticoduodenectomy. The patient demonstrated a good postoperative course, and was discharged from our hospital in remission 49 days after the surgery. Pathological findings confirmed that it was anaplastic pancreas carcinoma (giant cell type). After the surgery, we performed S-1 adjuvant chemotherapy 100 mg/day for four weeks, repeated similarly every six weeks for a total of four courses. We have followed this case for over 2 years so far with adjuvant chemotherapy, and no recurrence or metastasis has been revealed. Adjuvant chemotherapy with S-1 in patients with resected anaplastic carcinoma of the pancreas is also recommended as a result of Japan Adjuvant Study Group of Pancreatic Cancer 01(JASPAC-01) like the ordinary pancreatic ductal carcinomas. There is a possibility to achieve long-term survival in cases in which multidisciplinary treatment such as a curative resection and adjuvant chemotherapy are performed. PMID:27111877

  17. Short-term mortality in older patients treated with adjuvant chemotherapy for early-stage breast cancer.

    PubMed

    Rosenstock, Aron S; Lei, Xiudong; Tripathy, Debu; Hortobagyi, Gabriel N; Giordano, Sharon H; Chavez-MacGregor, Mariana

    2016-06-01

    Chemotherapy for early-stage breast cancer has lowered cancer recurrence and deaths. However, short-term mortality rates due to cancer or treatment in the general population remain largely unknown. In this study, we evaluate the short-term mortality rate and the determinants of such outcome among a cohort of older breast cancer patients treated with adjuvant chemotherapy. This is a population-based study based on the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare and the Texas Cancer Registry (TCR)-Medicare databases. Patients diagnosed with early-stage breast cancer between 2003 and 2011 who were 66 years or older and were treated with adjuvant chemotherapy within 6 months of diagnosis were included. Short-term mortality was defined as death from any cause within one year of breast cancer diagnosis. Descriptive statistics and multivariable logistic regression modeling were used for the analysis. Of the 21,536 patients included, a total of 625 (2.9 %) died within one year of breast cancer diagnosis. In multivariate analysis, older age (using 66-70 as reference category; 71-75 years OR 1.31, 95 % CI 1.05-1.62; 76-80 years OR 1.73, 95 % CI 1.36-2.19; >80 years OR 3.48, 95 % CI 2.7-4.48) and higher comorbidity index (using Charlson score of 0 as a reference, those with score of 1 or >2 had higher risk OR 1.46, 95 % CI 1.19-1.8 and OR 2.98, 95 % CI 2.42-3.67, respectively) were associated with the increased risk of short-term mortality. Other factors significantly associated with the outcome were higher grade and stage, ER-negative status, poor census tract area, and mastectomy. The findings of this study revealed that, in this large cohort of older breast cancer patients treated with adjuvant chemotherapy, 2.9 % of the population died within one year of breast cancer diagnosis. Finally, it was concluded that tumor- and patient-related characteristics were associated with short-term death. Our findings add relevant information that can be

  18. Irinotecan and capecitabine combination chemotherapy in a patient with triple-negative breast cancer relapsed after adjuvant chemotherapy with anthracycline and taxane.

    PubMed

    Lee, Anna; Go, Se-Il; Lee, Won Sup; Lee, Un Seok; Kim, Moon Jin; Kang, Myoung Hee; Lee, Gyeong-Won; Kim, Hoon-Gu; Kang, Jung Hun; Jeon, Kyung-Nyeo; Cho, Jae Min; Lee, Jeong-Hee

    2015-01-01

    The most effective regimen for taxane- and anthracycline-refractory triple-negative breast cancer (TNBC) has not yet been established. Capecitabine was approved by the US Food and Drug Administration for the treatment of advanced breast cancer and has shown efficacy in advanced breast cancer refractory to anthracyclines and taxanes. Irinotecan has synergism with 5-fluorouracil and shows efficacy in advanced breast cancer. Here we report on a patient with TNBC who relapsed with widespread bone and lung metastases shortly after adjuvant anthracycline followed by taxane chemotherapy. She achieved a metabolic complete response with irinotecan and capecitabine combination therapy and had 10 months' progression-free survival and 22 months' overall survival. She relapsed with and died of brain metastasis without any definite signs of progression of the lung and bone lesions she had had before the irinotecan and capecitabine combination therapy. To validate this favorable result, larger clinical trials are warranted in patients with metastatic or relapsed TNBC. PMID:25702650

  19. Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study.

    PubMed

    Zhang, Qing; Chen, Hong; Li, Qin; Zang, Yunjin; Chen, Xinguo; Zou, Weilong; Wang, Letian; Shen, Zhong-Yang

    2011-12-01

    The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m(2) on day 1, leucovorin (calcium folinate, CF) 200 mg/m(2) on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m(2) as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57 months by combination chemotherapy. The 1- and 3-year survival rates were 89.7% and 79.3% with chemotherapy versus 69.0% and 62.1% without chemotherapy. The cumulative 1-year survival was significantly increased by chemotherapy (log-rank test, P = 0.043). The 6-month tumor-free survival rate was 24.1% higher with chemotherapy than without. The recurrence rate after LT was significantly different between the two groups at 6 months (P = 0.036), but not at 3 years (P = 0.102). The chemotherapy regimen was generally well tolerated. Post-LT adjuvant chemotherapy with oxaliplatin/5-FU/CF could not prevent tumor recurrence post-LT but may contribute to improve the survival of HCC patients who do not meet the Milan criteria. These results should be verified in a larger sample with a longer follow-up period. PMID:21809025

  20. Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas

    PubMed Central

    Wild, Aaron T.; Dholakia, Avani S.; Fan, Katherine Y.; Kumar, Rachit; Moningi, Shalini; Rosati, Lauren M.; Laheru, Daniel A.; Zheng, Lei; De Jesus-Acosta, Ana; Ellsworth, Susannah G.; Hacker-Prietz, Amy; Voong, Khinh R.; Tran, Phuoc T.; Hruban, Ralph H.; Pawlik, Timothy M.; Wolfgang, Christopher L.

    2015-01-01

    Background Pancreatic adenosquamous carcinoma (PASC) accounts for only 1-4% of all exocrine pancreatic cancers and carries a particularly poor prognosis. This retrospective study was performed to determine whether inclusion of a platinum agent as part of adjuvant therapy is associated with improved survival in patients with resected PASC. Methods Records of all patients who underwent pancreatic resection at Johns Hopkins Hospital from 1986 to 2012 were reviewed to identify those with PASC. Multivariable Cox proportional hazards modeling was used to assess for significant associations between patient characteristics and survival. Results In total, 62 patients (1.1%) with resected PASC were identified among 5,627 cases. Median age was 68 [interquartile range (IQR), 57-77] and 44% were female. Multivariate analysis revealed that, among all patients (n=62), the following factors were independently predictive of poor survival: lack of adjuvant therapy [hazard ratio (HR) =3.6; 95% confidence interval (CI), 1.8-7.0; P<0.001], margin-positive resection (HR =3.5; 95% CI, 1.8-6.8; P<0.001), lymph node involvement (HR =3.5; 95% CI, 1.5-8.2; P=0.004), and age (HR =1.0; 95% CI, 1.0-1.1; P=0.035). There were no significant differences between patients who did and did not receive adjuvant therapy following resection (all P>0.05). A second multivariable model included only those patients who received adjuvant therapy (n=39). Lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.4; 95% CI, 1.0-5.8; P=0.040) and larger tumor diameter (HR =1.3; 95% CI, 1.0-1.6; P=0.047) were independent predictors of inferior survival. Conclusions Addition of a platinum agent to adjuvant regimens for resected PASC may improve survival among these high-risk patients, though collaborative prospective investigation is needed. PMID:25830031

  1. Chemotherapy

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Chemotherapy Chemotherapy (chemo) usually refers to the use of ... better sense of control over your cancer treatment. Chemotherapy Basics How Is Chemotherapy Used to Treat Cancer? ...

  2. Differential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without Paclitaxel

    PubMed Central

    Fountzilas, George; Dafni, Urania; Bobos, Mattheos; Batistatou, Anna; Kotoula, Vassiliki; Trihia, Helen; Malamou-Mitsi, Vassiliki; Miliaras, Spyros; Chrisafi, Sofia; Papadopoulos, Savvas; Sotiropoulou, Maria; Filippidis, Theodoros; Gogas, Helen; Koletsa, Triantafyllia; Bafaloukos, Dimitrios; Televantou, Despina; Kalogeras, Konstantine T.; Pectasides, Dimitrios; Skarlos, Dimosthenis V.; Koutras, Angelos; Dimopoulos, Meletios A.

    2012-01-01

    Background The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC). Materials and Methods Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5), and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67low); luminal B (ER/PgR-positive, HER2-negative, Ki67high); luminal-HER2 (ER/PgR-positive, HER2-positive); HER2-enriched (ER-negative, PgR-negative, HER2-positive); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive). Results After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS) and overall survival (OS) rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively) for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31–2.80, Wald's p = 0.001) and for death 2.53 (95% CI: 1.62–3.60, p<0.001). Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2

  3. Impact of Postoperative Radiation Therapy on Survival in Patients With Complete Resection and Stage I, II, or IIIA Non-Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: The Adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial

    SciTech Connect

    Douillard, Jean-Yves Rosell, Rafael; De Lena, Mario; Riggi, Marcello; Hurteloup, Patrick; Mahe, Marc-Andre

    2008-11-01

    Purpose: To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. Methods and Materials: ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non-small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survival was performed because this was an unplanned subgroup analysis. Results: Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). Conclusion: This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.

  4. The effect of comorbidity on the use of adjuvant chemotherapy and type of regimen for curatively resected stage III colon cancer patients.

    PubMed

    Hsieh, Mei-Chin; Thompson, Trevor; Wu, Xiao-Cheng; Styles, Timothy; O'Flarity, Mary B; Morris, Cyllene R; Chen, Vivien W

    2016-05-01

    Postsurgical chemotherapy is guideline-recommended therapy for stage III colon cancer patients. Factors associated with patients not receiving adjuvant chemotherapy were identified in numerous studies; comorbidity was recognized as an important factor besides patient's age. We assessed the association between comorbidity and the use of adjuvant chemotherapy and type of chemotherapy regimen. Stage III colon cancer patients who underwent surgical resection were obtained from ten Centers for Disease Control and Prevention (CDC)-NPCR Specialized Registries which participated in the Comparative Effectiveness Research (CER) project. Comorbidity was classified into no comorbidity recorded, Charlson, non-Charlson comorbidities, number, and severity of Charlson comorbidity. Pearson chi-square test and multivariable logistic regression were employed. Of 3180 resected stage III colon cancer patients, 64% received adjuvant chemotherapy. After adjusting for patient's demographic and tumor characteristics, there were no significant differences in receipt of chemotherapy between Charlson and non-Charlson comorbidity. However, patients who had two or more Charlson comorbidities or had moderate to severe disease were significantly less likely to have chemotherapy (ORs 0.69 [95% CI, 0.51-0.92] and 0.62 [95% CI, 0.42-0.91], respectively) when compared with those with non-Charlson comorbidity. In addition, those with moderate or severe comorbidities were more likely to receive single chemotherapy agent (P < 0.0001). Capecitabine and FOLFOX were the most common single- and multi-agent regimens regardless of type of comorbidity grouping. Both the number and severity of comorbidity were significantly associated with receipt of guideline-recommended chemotherapy and type of agent in stage III resected colon cancer patients. Better personalized care based on individual patient's condition ought to be recognized. PMID:26773804

  5. Prognostic Role of BRAF Mutation in Stage II/III Colorectal Cancer Receiving Curative Resection and Adjuvant Chemotherapy: A Meta-Analysis Based on Randomized Clinical Trials

    PubMed Central

    Cao, Ying; Fang, Xuefeng; Zhong, Chenhan; Li, Dan; Yuan, Ying

    2016-01-01

    Background and Objective Studies examining the prognostic value of the BRAF mutation on relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) in stage II/III colorectal cancer (CRC) patients receiving curative resection and adjuvant chemotherapy so far showed discrepant results. Therefore, a meta-analysis of relevant studies was performed for clarification. Methods Randomized trials of stage II/III colorectal cancer treated with curative resection followed by adjuvant chemotherapy were selected to conduct a meta-analysis. The necessary descriptive and statistical information such as hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from published survival data. Results Seven phase III randomized clinical trials (RCTs) including 1,035 BRAF mutation stage II/III CRC patients receiving curative resection and adjuvant chemotherapy were analyzed. Overall, BRAF mutation resulted in poorer OS (HR = 1.42, 95% CI: 1.25–1.60; P < 0.00001), and poorer DFS (HR = 1.26, 95% CI: 1.07–1.48, P = 0.006) compared with BRAF wild-type CRC. The prognostic role on RFS could not be elucidated in the meta-analysis because of limited data. Conclusions BRAF mutation was significantly related with shorter DFS and OS among stage II/III CRC patients receiving adjuvant chemotherapy after curative resection. Its prognostic role for RFS needs to be further analyzed when more data is available. PMID:27138801

  6. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.

    PubMed

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

  7. Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

    PubMed Central

    Kouloulias, Vassilis; Zygogianni, Anna; Kypraiou, Efrosini; Georgakopoulos, John; Thrapsanioti, Zoi; Beli, Ivelina; Mosa, Eftychia; Psyrri, Amanta; Antypas, Christos; Armbilia, Christina; Tolia, Maria; Platoni, Kalliopi; Papadimitriou, Christos; Arkadopoulos, Nikolaos; Gennatas, Costas; Zografos, George; Kyrgias, George; Dilvoi, Maria; Patatoucas, George; Kelekis, Nikolaos; Kouvaris, John

    2014-01-01

    AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ2 test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions. PMID:25405195

  8. Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70

    PubMed Central

    Lu, Chieh-Sheng; Chang, Ping-Ying; Chen, Yu-Guang; Chen, Jia-Hong; Wu, Yi-Ying; Ho, Ching-Liang

    2015-01-01

    Background The aim of this study was to examine the specific chemoregimens selected for adjuvant therapy in the patients with stage III colon cancer. We investigated the trends in chemotherapeutic prescribing patterns and looked for adequate therapeutic setting for these patients. Methods 288 patients presenting with stage III colon cancer and undergoing adjuvant therapies after curative surgery for more than 3-month were enrolled between January 2006 and December 2011. Demographic characteristics and therapeutic factors were analyzed, including age, gender, histological grade, tumor sizes, tumor location, pathologic stage, performance status, serum carcinoembryonic antigen, regimens selection, interval from the operation to the start of adjuvant therapy and prolonged adjuvant therapy. Kaplan– Meier methods were utilized for drawing survival curves and Cox model was used to analyze survival, prognostic factors. Results The analysis showed that the patients aged under 70 received more intensive therapies than those aged over 70 (P<0.001). Later, advanced analysis in therapeutic factors was conducted between the patients aged under 70 and those over 70. In the patients aged under 70, significant differences in 4-year overall survival (OS) were noted between UFUR (oral tegafur-uracil plus leucovorin) groups and FOLFOX (5-FU plus oxaliplatin) [65.6% versus (vs) 89.8%, relative risk (RR) 3.780, 95% confidence interval (CI) 1.263–11.315, P = 0.017]. There were also differences in 4-year OS between these patients with and without oxaliplatin-contained regimens (92.1% vs 83.4%, respectively, RR 0.385, 95% CI 0.157–0.946, P = 0.037). In addition, the patients who received intravenous or combined therapy also had higher 4-year OS than those only received oral regimens (92.1% vs 76.6%, P = 0.077), though the finding did not reach statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less

  9. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  10. Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer.

    PubMed Central

    Yu, W; Whang, I; Suh, I; Averbach, A; Chang, D; Sugarbaker, P H

    1998-01-01

    OBJECTIVE: Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy. This randomized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer. SUMMARY BACKGROUND DATA: Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients. Resection site and peritoneal surface spread, along with liver metastases, are the most common areas of recurrence. Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced. METHODS: In a prospective randomized trial of 248 patients, intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection. Patients who were thought to have stage II or stage III disease were randomized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy. After final pathologic examinations, there were 39 patients with stage I, 50 with stage II 95 with stage III, and 64 with resected stage IV cancer. RESULTS: The 5-year survival of the surgery-only group was 29.3%, and the surgery-plus-intraperitoneal chemotherapy group was 38.7% (p = 0.219). In a subset analysis, the patients with stage I, stage II, and stage IV disease showed no statistically significant difference in survival. The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4% versus a survival rate of 49.1% for patients who underwent surgery plus intraperitoneal chemotherapy (p = 0.011). CONCLUSIONS: In a subset analysis, patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy

  11. Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study

    PubMed Central

    Le Roy, Bertrand; Tixier, Lucie; Pereira, Bruno; Sauvanet, Pierre; Buc, Emmanuel; Pétorin, Caroline; Déchelotte, Pierre; Pezet, Denis; Balayssac, David

    2016-01-01

    Background Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. Methods This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb–IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. Results Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis

  12. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

    PubMed Central

    2011-01-01

    Abstract Background The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion The current protocol is feasible for achieving local control rates, as well as OS and

  13. Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: A Review of the National Cancer Data Base

    PubMed Central

    Robinson, Cliff G.; Patel, Aalok P.; Bradley, Jeffrey D.; DeWees, Todd; Waqar, Saiama N.; Morgensztern, Daniel; Baggstrom, Maria Q.; Govindan, Ramaswamy; Bell, Jennifer M.; Guthrie, Tracey J.; Colditz, Graham A.; Crabtree, Traves D.; Kreisel, Daniel; Krupnick, Alexander S.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

    2015-01-01

    Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. PMID:25667283

  14. A prospective cohort study of early discontinuation of adjuvant chemotherapy in women with breast cancer: the breast cancer quality of care study (BQUAL).

    PubMed

    Neugut, Alfred I; Hillyer, Grace Clarke; Kushi, Lawrence H; Lamerato, Lois; Buono, Donna L; Nathanson, S David; Bovbjerg, Dana H; Mandelblatt, Jeanne S; Tsai, Wei-Yann; Jacobson, Judith S; Hershman, Dawn L

    2016-07-01

    For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and reasons for early discontinuation of adjuvant chemotherapy in women with breast cancer. We conducted a prospective cohort study among three U.S. health care organizations. Of 1158 women with newly diagnosed non-metastatic breast cancer, 2006-2010, we analyzed 445 (38.4 %) patients who initiated standard adjuvant chemotherapy as defined by accepted guidelines. We interviewed patients at baseline and twice during treatment regarding sociodemographic/psychosocial factors and treatment decision-making and collected clinical data. They were categorized according to the number of cycles required by the chemotherapy regimen they had initiated. The outcome was early discontinuation (<80 % of planned cycles). Of patients analyzed, 392 (88.1 %) completed the prescribed therapy. The strongest predictor was receipt of a regimen entailing >4 cycles of therapy (18.1 % for longer regimens, 7.4 % for 4 cycles) (odds ratio [OR] 2.59, 95 % CI 1.32-5.08), controlling for race, age, stage, hormone receptor status, social support, optimism, spirituality, stress, and physical symptoms. Higher levels of psychological symptoms on the Memorial symptom assessment scale also increased the odds of early discontinuation (OR 1.92, 95 % CI 0.998-3.68). The large majority of patients who initiated adjuvant chemotherapy for breast cancer completed their prescribed regimens, but early discontinuation was associated with lengthier regimens and, with borderline statistical significance, for those with psychological side effects. PMID:27287779

  15. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  16. Neo-adjuvant chemotherapy plus surgery versus surgery alone for cervical cancer: Meta-analysis of randomized controlled trials.

    PubMed

    Peng, Yun-Hua; Wang, Xin-Xiu; Zhu, Jing-Song; Gao, Li

    2016-02-01

    The aim of this study was to evaluate the efficacy and safety of neo-adjuvant chemotherapy (NACT) versus radical surgery (RS) for patients with cervical cancer. A meta-analysis of randomized controlled trials (RCT) of NACT + RS versus RS alone for patients with cervical cancer was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The following electronic databases were searched from their inception to April 2015: PUBMED, EMBASE and Cochrane Library. Statistical analysis was done using REVIEW MANAGER 5.3. Five RCT involving 739 patients were studied. There were significant differences between the NACT + RS and the RS-alone groups for positive lymph nodes (OR, 0.45; 95%CI: 0.29-0.70) and parametrial infiltration (OR, 0.48; 95% CI: 0.25-0.92), while treatment efficacy did not differ significantly for 5-year overall survival rate (OR, 1.17; 95% CI: 0.85-1.61), 5-year disease-free survival rate (OR, 1.09; 95% CI: 0.77-1.56) or recurrence rate (OR, 1.17; 95% CI: 0.85-1.61). The results also indicated that chemotherapy-related toxicity was well tolerated. For patients with cervical cancer, NACT could significantly reduce the number of positive lymph nodes and the level of parametrial infiltration compared with RS alone, and be well tolerated. PMID:26807961

  17. Neoadjuvant and adjuvant chemotherapy combined with anatomical resection of feline injection-site sarcoma: results in 21 cats.

    PubMed

    Bray, J; Polton, G

    2016-06-01

    This study assesses the outcome of two combined treatment strategies for the treatment of feline injection-site sarcoma (FISS). Twenty-one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m(-2) ), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co-axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow-up was performed by telephone contact with a median follow-up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour-free survival and disease-free interval. PMID:24502401

  18. Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer

    PubMed Central

    Turan, Nedim; Benekli, Mustafa; Dane, Faysal; Unal, Olcun Umit; Kara, Hasan Volkan; Koca, Dogan; Balvan, Ozlem; Eren, Tulay; Tastekin, Didem; Helvaci, Kaan; Berk, Veli; Demirci, Umut; Ozturk, Selcuk Cemil; Dogan, Erkan; Cetin, Bulent; Kucukoner, Mehmet; Tonyali, Onder; Tufan, Gulnihal; Oztop, Ilhan; Gumus, Mahmut; Coskun, Ugur; Uner, Aytug; Ozet, Ahmet; Buyukberber, Suleyman

    2014-01-01

    Introduction We investigated the impact of modern chemotherapy regimens and bevacizumab following pulmonary metastasectomy (PM) from metastatic colorectal cancer (CRC). Methods A total of 122 consecutive patients who were curatively resected for pulmonary metastases of CRC in twelve oncology centers were retrospectively analysed between January 2000 and April 2012. Results Of 122 patients, 14 did not receive any treatment following PM. The remaining 108 patients received fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) chemotherapy combinations. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). Median recurrence-free survival (RFS) was 17 months and median overall survival (OS) has not been reached at a median follow-up of 25 months after PM. Three and five-year OS rates were 66% and 53%, respectively. RFS and OS were similar, irrespective of the chemotherapy regimen or BEV use. Positive pulmonary margin, KRAS mutation status, and previous liver metastasectomy were negative independent prognostic factors for RFS, while pathologically confirmed thoracic lymph node involvement was the only negative independent prognostic for OS in multivariate analysis. Conclusions No significant RFS or OS difference was observed in respect to chemotherapy regimens with or without BEV in patients with pulmonary metastases of CRC following curative resection. PMID:26763794

  19. Robotic Stereotactic Radioablation Concomitant With Neo-Adjuvant Chemotherapy for Breast Tumors

    SciTech Connect

    Bondiau, Pierre-Yves; Bahadoran, Phillipe; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Chamorey, Emmanuel; Courdi, Adel; Quielle-Roussel, Catherine; Thariat, Juliette; Ferrero, Jean-Marc

    2009-11-15

    Purpose: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. Materials and Methods: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. Results: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. Conclusion: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

  20. Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: an update.

    PubMed

    Horning, S J; Rosenberg, S A; Hoppe, R T

    1996-01-01

    From May 1989 to August 1995, 94 previously untreated patients with Hodgkin's disease stage II with bulky mediastinal involvement (n = 28) or stage III or IV (n = 66) received an abbreviated chemotherapy regimen, Stanford V, +/-radiotherapy (RT). Chemotherapy was given weekly for 12 weeks followed by consolidative RT to sites of initial bulky disease. With a median follow-up of 3 years, the actuarial 6-year survival is 93% and the freedom from progression is 89%. There have been no relapses or deaths among the 28 patients with stage II bulky mediastinal disease. Eight relapses and three deaths have occurred in the group of 66 patients with stage III-IV disease. The abbreviated chemotherapy regimen, Stanford V, in combination with RT is well tolerated and highly effective therapy for bulky, limited stage and advanced stage HD. Lower cumulative exposure to alkylating agents, doxorubicin, bleomycin and limited use of radiation is expected to improved the prospects for fertility and decrease the risks for second neoplasms and late cardiopulmonary toxicity. PMID:8836420

  1. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

    PubMed

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  2. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs

    PubMed Central

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27–87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  3. Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

    PubMed

    Kuranishi, Fumito; Ohno, Tadao

    2013-01-01

    Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease. PMID:23734861

  4. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) (follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 ..beta..-estradiol (E/sub 2/) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E/sub 2/ (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E/sub 2/, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  5. Adjuvant chemotherapy for colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

    PubMed

    Kountourakis, Panteleimon; Souglakos, John; Gouvas, Nikolaos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Boukovinas, Ioannis; Christodoulou, Christos; Chrysou, Evangelia; Dervenis, Christos; Emmanouilidis, Christos; Georgiou, Panagiotis; Karachaliou, Niki; Katopodi, Ourania; Makatsoris, Thomas; Papakostas, Pavlos; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Tekkis, Paris; Triantopoulou, Charina; Tzardi, Maria; Vassiliou, Vassilios; Vini, Louiza; Xynogalos, Spyridon; Xynos, Evaghelos; Ziras, Nikolaos; Papamichael, Demetris

    2016-01-01

    Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered. PMID:26751386

  6. Adjuvant chemotherapy for colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO*

    PubMed Central

    Kountourakis, Panteleimon; Souglakos, John; Gouvas, Nikolaos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Boukovinas, Ioannis; Christodoulou, Christos; Chrysou, Evangelia; Dervenis, Christos; Emmanouilidis, Christos; Georgiou, Panagiotis; Karachaliou, Niki; Katopodi, Ourania; Makatsoris, Thomas; Papakostas, Pavlos; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Tekkis, Paris; Triantopoulou, Charina; Tzardi, Maria; Vassiliou, Vassilios; Vini, Louiza; Xynogalos, Spyridon; Xynos, Evaghelos; Ziras, Nikolaos; Papamichael, Demetris

    2016-01-01

    Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered. PMID:26751386

  7. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    PubMed

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  8. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  9. Protective effect of rPb40 as an adjuvant for chemotherapy in experimental paracoccidioidomycosis.

    PubMed

    Fernandes, V C; Martins, E M N; Boeloni, J N; Serakides, R; Goes, A M

    2012-08-01

    The conventional treatment for the most prevalent mycosis in Latin America, paracoccidioidomycosis (PCM), involves long periods of therapy that results in side effects and a high frequency of relapses. The search for a new, alternative treatment is necessary. Pb40 is an antigenic protein from P. brasiliensis fraction F0. This fraction has already been shown to have significant protective activity when used as a PCM vaccine in experimental models. The complete cDNA sequence corresponding to Pb40 was cloned into a pET-21a plasmid, expressed in E. coli with a his-tag and purified by affinity chromatography. The predicted protein sequence exhibited nearly 100% homology to a fragment of the hypothetical EF-hand domain containing protein of P. brasiliensis. Immunization with this recombinant protein was used together with chemotherapy in an attempt to improve PCM treatment. The combined drug/rPb40 treatment exhibited long-lasting control of PCM in the liver and spleen and largely preserved the tissue structures of these organs. Despite the lack of a reduction in CFUs in the group that received the combined treatment, there was a significant reduction in the size of the lesions in the lungs after 70 days of infection. At the same time, the IL-10 levels were higher in the treated mice than in the infected-only mice. Moreover, significant levels of rPb40-specific IgG antibodies were detected in the sera of immunized mice. Thus, the treatment protocol consisting of rPb40 immunization in addition to fluconazole chemotherapy showed an additive protective effect after intratracheal challenge, preventing fungal dissemination to other sites of infection and preventing relapses. These results provide new prospects for PCM immunotherapy. PMID:22391822

  10. Adjuvant Therapeutic Modalities in Primary Small Cell Carcinoma of Esophagus Patients

    PubMed Central

    Zou, Bingwen; Li, Tao; Zhou, Qiang; Ma, Daiyuan; Chen, Yongshun; Huang, Meijuan; Peng, Feng; Xu, Yong; Zhu, Jiang; Ding, Zhenyu; Zhou, Lin; Wang, Jin; Ren, Li; Yu, Min; Gong, Youling; Li, Yanying; Chen, Longqi; Lu, You

    2016-01-01

    Abstract To evaluate the treatment pattern and survival of patients receiving radical resection for primary small cell carcinoma of the esophagus (PSCCE). This retrospective study included 150 patients who received radical resection of PSCCE. Data were retrieved from 4 centers in Western China. Thirty-nine of 150 patients received postoperative chemo-radiotherapy, 62 received postoperative chemotherapy, and 49 received radical resection only. The median radiation dosage was 50 Gy. The chemotherapeutic regimen was platinum-based and lasted for 2 to 6 cycles (median, 3). Median disease-free survival (mDFS) and overall survival (mOS) were 12.0 and 18.3 months, respectively. Subgroup analysis revealed that postoperative therapy did not improve survival in limited stage I (LSI) disease, whereas postoperative chemotherapy improved survival in limited stage II (LSII) disease. Relative to chemotherapy alone, chemoradiotherapy did not improve survival in patients with completely resected LSII disease. A multivariate analysis indicated an association of no postoperative chemotherapy with shorter DFS (P = 0.050) and OS (P = 0.010). Higher lymph node stage and length of disease longer than 3 cm were poor prognostic factors for both DFS and OS. Adjuvant chemotherapy improves survival in PSCCE patients with completely resected LSII disease. Adjuvant treatment with postoperative chemotherapy alone or postoperative chemo-radiotherapy does not increase survival in completely resected LSI disease. PMID:27124057

  11. Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial.

    PubMed

    Tröger, Wilfried; Zdrale, Zdravko; Tišma, Nevena; Matijašević, Miodrag

    2014-01-01

    Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the secondary objective was neutropenia. Here we report the comparison of HxA (n = 34) versus untreated control (n = 31). Results. In the explorative analysis ten of 15 scores of the EORTC QLQ-C30 showed a better quality of life in the HxA group compared to the control group (P < 0.001 to P = 0.038 in Dunnett-T3 test). The difference was clinically relevant (difference of at least 5 points, range 5.4-12.2) in eight of the ten scores. Neutropenia occurred in 7/34 HxA patients and in 8/31 control patients (P = 0.628). Conclusions. This pilot study showed an improvement of quality of life by treating breast cancer patients with HxA additionally to CAF. Although the open design may be a limitation, the findings show the feasibility of a confirmatory study using the methods described here. PMID:24701238

  12. Therapeutic Usefulness of Postoperative Adjuvant Chemotherapy with Tegafur–Uracil (UFT) in Patients with Breast Cancer: Focus on the Results of Clinical Studies in Japan

    PubMed Central

    Noguchi, Shinzaburo

    2010-01-01

    In Japan, the history of postoperative chemotherapy for breast cancer started with 5-fluorouracil (5-FU), launched in the 1980s. Currently, oral fluoropyrimidine–based regimens indicated for the treatment of breast cancer in Japan include tegafur plus uracil (UFT); tegafur, gimeracil, and oteracil (TS-1); doxifluridine; and capecitabine. In particular, UFT represents an important option for long-term treatment because of minimal adverse events and the potential for long-term maintenance of effective plasma concentrations of 5-FU to inhibit micrometastasis after surgery. Therefore, various clinical studies of postoperative adjuvant chemotherapy with UFT have been conducted in patients with completely resected tumors. Recent studies have shown that UFT prolongs survival after tumor resection in patients with gastric cancer, colorectal cancer, and lung cancer. In patients with breast cancer, large clinical trials of UFT-based postoperative chemotherapy conducted in Japan have shown that UFT is useful for the treatment of intermediate-risk patients with no lymph node metastasis. This paper reviews the results of clinical studies of UFT conducted in Japan to assess the therapeutic usefulness of this oral 5-FU. The types of patients most likely to benefit from UFT are discussed on the basis of currently available evidence and a global consensus of treatment recommendations. The optimal timing of endocrine therapy and strategies for postoperative adjuvant chemotherapy with UFT in patients with breast cancer are also discussed. PMID:20080863

  13. Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial

    PubMed Central

    Tröger, Wilfried; Ždrale, Zdravko; Tišma, Nevena; Matijašević, Miodrag

    2014-01-01

    Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the secondary objective was neutropenia. Here we report the comparison of HxA (n = 34) versus untreated control (n = 31). Results. In the explorative analysis ten of 15 scores of the EORTC QLQ-C30 showed a better quality of life in the HxA group compared to the control group (P < 0.001 to P = 0.038 in Dunnett-T3 test). The difference was clinically relevant (difference of at least 5 points, range 5.4–12.2) in eight of the ten scores. Neutropenia occurred in 7/34 HxA patients and in 8/31 control patients (P = 0.628). Conclusions. This pilot study showed an improvement of quality of life by treating breast cancer patients with HxA additionally to CAF. Although the open design may be a limitation, the findings show the feasibility of a confirmatory study using the methods described here. PMID:24701238

  14. Patterns of Care in the Administration of Neo-adjuvant Chemotherapy for Breast Cancer. A Population-Based Study.

    PubMed

    Vugts, Guusje; Maaskant-Braat, Adriana J G; Nieuwenhuijzen, Grard A P; Roumen, Rudi M H; Luiten, Ernest J T; Voogd, Adri C

    2016-05-01

    Neo-adjuvant chemotherapy (NAC) is used to facilitate radical surgery for initially irresectable or locally advanced breast cancer. The indication for NAC has been extended to clinically node negative (cN0) patients in whom adjuvant systemic therapy is foreseen. A population-based study was conducted to evaluate the increasing use of NAC, breast conserving surgery (BCS) after NAC and timing of the sentinel node biopsy (SNB). All female breast cancer patients, treated in 10 hospitals in the Eindhoven Cancer Registry area in the Netherlands between January 2003 and June 2012 were included (N = 18,427). In total, 1,402 patients (7.6%) received NAC. The administration increased from 2.5% in 2003 to 13.0% in 2011 (p < 0.001). Use of NAC increased from 0.5% to 2.3% for cT1 tumors, from 2.8% to 27.0% for cT2, from 30.6% to 70.9% for cT3, and from 40.5% to 58.1% for cT4 tumors (p < 0.001). In cN0 patients, use of NAC increased from 1.0% to 4.4% and in clinically node positive patients from 12.0% to 57.5% (p < 0.001). Downsizing of the tumor and BCS are achieved increasingly. In 2011, in three hospitals NAC was administered in <10% of patients, in five hospitals in 10-15% and in two hospitals the proportion of patients receiving NAC was >20% (p < 0.001). Of the 1,402 patients with NAC, 495 patients underwent SNB, 91.5% of whom prior to NAC. In the Netherlands up to one in eight patients receive NAC. The administration of NAC and the percentage of BCS increased over the past decade, especially in cT2 tumors. Considerable hospital variation in the administration of NAC exists. PMID:26945566

  15. Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover

    PubMed Central

    Wilson, Caroline; Gossiel, Fatma; Leonard, Robert; Anderson, Richard A; Adamson, Douglas J A; Thomas, Geraldine; Coleman, Robert E

    2016-01-01

    Background The Ovarian Protection Trial In Premenopausal Breast Cancer Patients “OPTION” trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6–8 cycles of (neo)adjuvant chemotherapy (CT) +/− goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CT+/-G on markers of bone turnover. Methods Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (≤40 vs >40 years) and with exploratory analysis according to POI rates at 12 months. Results In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CT+G (40.81 vs 57.82 p=0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CT+G, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CT+G 5.845 vs CT 8.5 p=0.0006). These changes were predominantly seen in women >40 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses. Conclusion Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI. PMID:26998426

  16. Cardiac Tolerability of Concurrent Administration of Trastuzumab and Anthracycline-Based Regimen as Adjuvant Chemotherapy for Breast Cancer

    PubMed Central

    Watanabe, Naoki; Otsuka, Shoko; Sasaki, Yoko; Shimojima, Reiko; Wani, Yoji; Uchino, Kaori

    2014-01-01

    Summary Background Retrospective analysis suggests that anthracycline-containing regimens may be superior to non-anthracycline-containing regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, both trastuzumab and anthracycline have cardiotoxicity, and it remains unclear how to use trastuzumab in combination with an anthracycline to curtail their cardiotoxicity. Patients and Methods From 2010 to 2013, we administered weekly (q1w) paclitaxel (wP) followed by 75 mg/m2 epirubicin, fluorouracil, and cyclophosphamide (FEC) every third week (q3w) and concurrent q1w trastuzumab (H) to 41 patients with HER2-positive breast cancer (H+ group), and wP followed by FEC100 without trastuzumab to 57 patients who were HER2-negative (H– group). We routinely assessed the left ventricular ejection fraction (LVEF) by echocardiography, at the time of initiation, after wP, and after FEC, and compared them between these 2 groups. Results LVEF decreased from 63.2 to 60.9% (p = 0.030) in the H+ group and from 63.9 to 61.9% (p = 0.009) in the H– group. These 2 groups showed no significant difference in the reduction rate of LVEF over the period of chemotherapy (0.968 vs. 0.978: NS, p = 0.6457). There was no severe cardiotoxicity or congestive heart failure in either group. Conclusion Concurrent administration of epirubicin (q3w, 75 mg/m2) and trastuzumab showed no less cardiac tolerability in an adjuvant setting. PMID:24803887

  17. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC)

    PubMed Central

    Oki, E.; Murata, A.; Yoshida, K.; Maeda, K.; Ikejiri, K.; Munemoto, Y.; Sasaki, K.; Matsuda, C.; Kotake, M.; Suenaga, T.; Matsuda, H.; Emi, Y.; Kakeji, Y.; Baba, H.; Hamada, C.; Saji, S.; Maehara, Y.

    2016-01-01

    Backgrounds Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. Patients and methods The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. Results In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. Conclusion One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection. PMID:27056996

  18. Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk primary operable breast cancer--a quality assessment study.

    PubMed

    Svane, Inge M; Homburg, Keld M; Kamby, Claus; Nielsen, Dorte L; Roer, Ole; Sliffsgaard, Dorte; Johnsen, Hans E; Hansen, Steen W

    2002-01-01

    From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support was used as an adjuvant treatment strategy for management of primary high-risk breast cancer patients with more than five positive nodes. This single institution study included 52 women aged < or = 56 years with primary operable breast cancer and > or = 6 tumour-positive axillary lymph nodes. The treatment regimen consisted of at least three initial courses of FEC (5-fluorouracil, epirubicin, cyclophosphamide) followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral blood stem-cell reinfusion. This study focuses on quality control including evaluation of toxicity, supportive therapy and assessment of the stem-cell products. Cytokeratin 19 positive cells were found in the stem-cell product from 3/37 patients. Data regarding organ toxicity were used for evaluation of short- and long-term side effects. Substantial acute toxicity and frequent catheter-related infections were found. Long-term toxicities included reduced lung diffusion capacity (n = 36), fatigue (n = 14), arthralgia/myalgia (n = 10), neurotoxicity (n = 9) and memory loss (n = 4). However, most toxicities were grade 1-2 and reversible within two years. No treatment-related death occurred. Within a median follow-up of 30 months (range, 11-57), 25% of the patients had relapsed. Recurrence-free survival was 75% and overall survival was 88% three years after the start of treatment. Overall, high-dose chemotherapy was relatively well tolerated, with manageable toxicity and an acceptable requirement of supportive therapy. Until now, high-dose chemotherapy has not proven superior to conventional-dose adjuvant chemotherapy, therefore it is necessary in the future to focus on well-designed randomized studies. PMID:14651213

  19. [Adjuvant Systemic Chemotherapy with S-1/Oxaliplatin or mFOLFOX6 after Curative Resection of Distant Metastases in Patients with Colorectal Cancer].

    PubMed

    Miyata, Ryohei; Kameyama, Noriaki; Tomita, Masato; Mitsuhashi, Hiroaki; Baba, Shigeaki; Amada, En

    2016-03-01

    This study was aimed to assess the feasibility and short-term outcomes of adjuvant systemic chemotherapy with either S-1/oxaliplatin (SOX) or mFOLFOX6 (FOLFOX)after curative resection of distant metastases from colorectal cancer. We retrospectively examined 16 patients who underwent R0 resection of colorectal metastases, including the liver (n=6), lung (n=5), lymph node (n=3), and peritoneum (n=2), followed by chemotherapy with SOX (n=7) or FOLFOX (n=9) until disease progression. The mean recurrence-free survival was 13.2 months in the SOX group and 16.9 months in the FOLFOX group. The mean overall survival was 17.9 and 22.9 months, respectively. The number of given courses were 6.5 and 11.0, respectively. Although sensory neuropathy was observed in 38% of the patients, relative dose intensity was higher than 80%. Adjuvant chemotherapy with SOX or FOLFOX was feasible and effective. Further randomized prospective trials are warranted to confirm these results. PMID:27067848

  20. A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium

    PubMed Central

    Jhingran, Anuja; Ramondetta, Lois M.; Bodurka, Diane C.; Slomovitz, Brian M.; Brown, Jubilee; Levy, Lawrence B.; Garcia, Michael E.; Eifel, Patricia J.; Lu, Karen H.; Burke, Thomas W.

    2015-01-01

    Objective To prospectively evaluate tumor control, survival, and toxic effects in patients with International Federation of Gynecology and Obstetrics (1988) stage I-IIIA papillary serous carcinoma of the endometrium treated with concurrent chemoradiation and adjuvant chemotherapy. Methods Thirty-two patients were enrolled from October 2001 through July 2009. Patients underwent full surgical disease staging and postoperative concurrent weekly paclitaxel (50 mg/m2) and pelvic RT to 45 Gy plus a vaginal cuff boost followed by 4 cycles of adjuvant paclitaxel (135 mg/m2). Results Thirty patients (94%) were evaluable (3 with stage IA disease, 11 IB, 3 IC, 1 IIB, and 12 IIIA). Eighteen patients (60%) received all 5 planned courses of concurrent chemotherapy, 10 (33%) received 4 courses, and 2 (7%) received 3 courses. All 30 patients received RT; 27 (90%) received the full dose, 2 received 43.2 Gy, and 1 received 39.6 Gy owing to toxic effects. Twenty-three patients (77%) completed all 4 cycles of adjuvant paclitaxel, 3 (10%) completed 3 cycles, 2 (7%) completed 2 cycles, and 2 received no adjuvant therapy. Overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 93%, 87%, and 87%, respectively, at 2 years and 85%, 83%, and 87%, respectively, at 5 years. Six patients developed (20%) grade 3/4 toxcities from the treatment. Four patients (13%) had grade 3 or more severe bowel complications and two patients developed symptomatic pelvic fractures. Conclusions Treatment with concurrent paclitaxel and pelvic RT followed by 4 courses of systemic paclitaxel produced favorable results in patients with surgically staged I-III UPSC. PMID:23385150

  1. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

    SciTech Connect

    Burstein, Harold J. . E-mail: hburstein@partners.org; Bellon, Jennifer R.; Galper, Sharon; Lu, H.-M.; Kuter, Irene; Wong, Julia; Gelman, Rebecca; Bunnell, Craig A.; Parker, Leroy M.; Garber, Judy E.; Winer, Eric P.; Harris, Jay R.; Powell, Simon N.

    2006-02-01

    Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly x 12 weeks (60 mg/m{sup 2}), or every 3 weeks x 4 cycles (135-175 mg/m{sup 2}). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m{sup 2} per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m{sup 2}. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

  2. Update in Cancer Chemotherapy: Genitourinary Tract Cancer, Part 4: Testicular Cancer

    PubMed Central

    Wright, Jane C.

    1988-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 4 is a review of treatments for cancer of the testicles. Testicular cancer is highly curable and responds well to both surgery and chemotherapy. Patients with stage I and stage II nonseminomatous germ-cell tumors may be cured by surgery alone or in combination with chemotherapy. In patients with pathologic stage II disease, the use of adjuvant chemotherapy with two courses of platinum-based combination drugs has been successful in preventing relapse. Further refinements in management and research could banish the problem of testicular cancer. PMID:3290501

  3. A clinical prognostic scoring system for resectable gastric cancer to predict survival and benefit from paclitaxel- or oxaliplatin-based adjuvant chemotherapy

    PubMed Central

    Qian, Jing; Qian, Yingying; Wang, Jian; Gu, Bing; Pei, Dong; He, Shaohua; Zhu, Fang; Røe, Oluf Dimitri; Xu, Jin; Liu, Lianke; Gu, Yanhong; Guo, Renhua; Yin, Yongmei; Shu, Yongqian; Chen, Xiaofeng

    2016-01-01

    Background Gastrectomy with D2 lymphadenectomy is a standard procedure of curative resection for gastric cancer (GC). The aim of this study was to develop a simple and reliable prognostic scoring system for GC treated with D2 gastrectomy combined with adjuvant chemotherapy. Methods A prognostic scoring system was established based on clinical and laboratory data from 579 patients with localized GC without distant metastasis treated with D2 gastrectomy and adjuvant chemotherapy. Results From the multivariate model for overall survival (OS), five factors were selected for the scoring system: ≥50% metastatic lymph node rate, positive lymphovascular invasion, pathologic TNM Stage II or III, ≥5 ng/mL preoperative carcinoembryonic antigen level, and <110 g/L preoperative hemoglobin. Two models were derived using different methods. Model A identified low- and high-risk patients for OS (P<0.001), while Model B differentiated low-, intermediate-, and high-risk patients for OS (P<0.001). Stage III patients in the low-risk group had higher survival probabilities than Stage II patients. Both Model A (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.69–0.78) and Model B (AUC: 0.79, 95% CI: 0.72–0.83) were better predictors compared with the pathologic TNM classification (AUC: 0.62, 95% CI: 0.59–0.71, P<0.001). Adjuvant paclitaxel- or oxaliplatin-based or triple chemotherapy showed significantly better outcomes in patients classified as high risk, but not in those with low and intermediate risk. Conclusion A clinical three-tier prognostic risk scoring system was established to predict OS of GC treated with D2 gastrectomy and adjuvant chemotherapy. The potential advantage of this scoring system is that it can identify high-risk patients in Stage II or III who may benefit from paclitaxel- or oxaliplatin-based regimens. Prospective studies are needed to confirm these results before they are applied clinically. PMID:26966350

  4. Adjuvant Chemotherapy With or Without Pelvic Radiotherapy After Simultaneous Surgical Resection of Rectal Cancer With Liver Metastases: Analysis of Prognosis and Patterns of Recurrence

    SciTech Connect

    An, Ho Jung; Yu, Chang Sik; Yun, Sung-Cheol; Kang, Byung Woog; Hong, Yong Sang; Lee, Jae-Lyun; Ryu, Min-Hee; Chang, Heung Moon; Park, Jin Hong; Kim, Jong Hoon; Kang, Yoon-Koo; Kim, Jin Cheon; Kim, Tae Won

    2012-09-01

    Purpose: To investigate the outcomes of adjuvant chemotherapy (CT) or chemoradiotherapy (CRT) after simultaneous surgical resection in rectal cancer patients with liver metastases (LM). Materials and Methods: One hundred and eight patients receiving total mesorectal excision for rectal cancer and surgical resection for LM were reviewed. Forty-eight patients received adjuvant CRT, and 60 were administered CT alone. Recurrence patterns and prognosis were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were compared between the CRT and CT groups. The inverse probability of the treatment-weighted (IPTW) method based on the propensity score was used to adjust for selection bias between the two groups. Results: At a median follow-up period of 47.7 months, 77 (71.3%) patients had developed recurrences. The majority of recurrences (68.8%) occurred in distant organs. By contrast, the local recurrence rate was only 4.7%. Median DFS and OS were not significantly different between the CRT and CT groups. After applying the IPTW method, we observed no significant differences in terms of DFS (hazard ratio [HR], 1.347; 95% confidence interval [CI], 0.759-2.392; p = 0.309) and OS (HR, 1.413; CI, 0.752-2.653; p = 0.282). Multivariate analyses showed that unilobar distribution of LM and normal preoperative carcinoembryonic antigen level (<6 mg/mL) were significantly associated with longer DFS and OS. Conclusions: The local recurrence rate after simultaneous resection of rectal cancer with LM was relatively low. DFS and OS rates were not different between the adjuvant CRT and CT groups. Adjuvant CRT may have a limited role in this setting. Further prospective randomized studies are required to evaluate optimal adjuvant treatment in these patients.

  5. Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

    PubMed Central

    Gandhi, S.; Fletcher, G.G.; Eisen, A.; Mates, M.; Freedman, O.C.; Dent, S.F.; Trudeau, M.E.

    2015-01-01

    Background The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)–directed therapy. Methods For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite–based regimens (for example, cyclophosphamide–methotrexate–5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline–taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and

  6. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy.

    PubMed

    Srivastava, Amit Kumar; Wang, Qi-En

    2016-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy. PMID:27308560

  7. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy

    PubMed Central

    Srivastava, Amit Kumar; Wang, Qi-En

    2016-01-01

    ABSTRACT Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy.

  8. Cost-effectiveness of adjuvant chemotherapy with uracil–tegafur for curatively resected stage III rectal cancer

    PubMed Central

    Hisashige, A; Yoshida, S; Kodaira, S

    2008-01-01

    Recently, the National Surgical Adjuvant Study of Colorectal Cancer in Japan, a randomised controlled trial of oral uracil–tegafur (UFT) adjuvant therapy for stage III rectal cancer, showed remarkable survival gains, compared with surgery alone. To evaluate value for money of adjuvant UFT therapy, cost-effective analysis was carried out. Cost-effectiveness analysis of adjuvant UFT therapy was carried out from a payer's perspective, compared with surgery alone. Overall survival and relapse-free survival were estimated by Kaplan–Meier method, up to 5.6 years from randomisation. Costs were estimated from trial data during observation. Quality-adjusted life-years (QALYs) were calculated using utility score from literature. Beyond observation period, they were simulated by the Boag model combined with the competing risk model. For 5.6-year observation, 10-year follow-up and over lifetime, adjuvant UFT therapy gained 0.50, 0.96 and 2.28 QALYs, and reduced costs by $2457, $1771 and $1843 per person compared with surgery alone, respectively (3% discount rate for both effect and costs). Cost-effectiveness acceptability and net monetary benefit analyses showed the robustness of these results. Economic evaluation of adjuvant UFT therapy showed that this therapy is cost saving and can be considered as a cost-effective treatment universally accepted for wide use in Japan. PMID:18797469

  9. Loss of ataxia-telangiectasia-mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer.

    PubMed

    Suh, Koung Jin; Ryu, Han Suk; Lee, Kyung-Hun; Kim, Hyojin; Min, Ahrum; Kim, Tae-Yong; Yang, Yaewon; Moon, Hyeong-Gon; Han, Sae-Won; Oh, Do-Youn; Han, Wonshik; Park, In Ae; Noh, Dong-Young; Im, Seock-Ah

    2016-07-01

    We investigated the correlation of ataxia-telangiectasia-mutated (ATM) protein expression with clinicopathological features and prognosis in patients with breast cancer. ATM expression was determined by immunohistochemistry in 420 surgically resected breast tumors. ATM loss was observed in 126/407 evaluable cases (31.0 %), and was significantly associated with larger tumor size, lymph node metastasis, higher tumor grade, and ER- and/or PR-negative status. ATM loss was also associated with significantly lower disease-free survival rates than those in patients with intact ATM (5-year disease-free survival rate 81.2 vs. 90.7 %, p = 0.015). In multivariate analysis, ATM loss combined with abnormal p53 expression was an independent predictor of shorter disease-free survival [hazard ratio (HR) 3.48; 95 % confidence interval (CI), 1.48-8.17, p = 0.004]. A tendency towards a poorer prognosis was observed for tumoral ATM loss alone, although statistical significance was not reached (HR 1.74; 95 % CI 0.95-3.20; p = 0.075). In subgroup analysis, ATM loss was associated with shorter disease-free survival in patients who did not receive adjuvant anthracycline chemotherapy (5-year disease-free survival rate 92.7 % in intact ATM group vs. 68.1 % in ATM loss group, p = 0.002), but this poor prognosis was overcome in patients who did (5-year disease-free survival rate 89.8 vs. 84.4 %, p = 0.243), suggesting more benefit from anthracycline-based chemotherapy. Tumors with loss of ATM expression have a poor prognosis and their prognoses are dependent on the use of adjuvant anthracycline. ATM loss might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy. PMID:27329169

  10. MGMT Promoter Methylation Is Prognostic but Not Predictive for Outcome to Adjuvant PCV Chemotherapy in Anaplastic Oligodendroglial Tumors: A Report From EORTC Brain Tumor Group Study 26951

    PubMed Central

    van den Bent, Martin J.; Dubbink, Hendrikus J.; Sanson, Marc; van der Lee-Haarloo, Cathleen R.; Hegi, Monika; Jeuken, Judith W.M.; Ibdaih, Ahmed; Brandes, Alba A.; Taphoorn, Martin J.B.; Frenay, Marc; Lacombe, Denis; Gorlia, Thierry; Dinjens, Winand N.M.; Kros, Johan M.

    2009-01-01

    Purpose O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT). Patients and Methods In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification. Results In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed. Conclusion In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma. PMID:19901104

  11. Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.

    PubMed

    Adams, Scott C; Segal, Roanne J; McKenzie, Donald C; Vallerand, James R; Morielli, Andria R; Mackey, John R; Gelmon, Karen; Friedenreich, Christine M; Reid, Robert D; Courneya, Kerry S

    2016-08-01

    The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n = 70), AET (n = 64), or RET (n = 66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32 kg/m(2); p = 0.017), UE-MD (0.12 kg/kg; p < 0.001), and LE-MD (0.27 kg/kg; p < 0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p = 0.039) and dynapenia (p = 0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95 % confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95 % CI -4.0 to 24.1]), and fatigue (5.3 points [95 % CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL. PMID:27394134

  12. Adjuvant treatment

    PubMed Central

    Sultana, Asma; Neoptolemos, John

    2006-01-01

    Exocrine pancreatic cancer (pancreatic ductal adenocarcinoma) is one of the leading causes of cancer deaths in the western world, accounting for 5% of all cancer-related deaths. Only a small percentage of patients with pancreatic cancer are able to undergo potentially curative resection, even in specialized centres, and prognosis remains poor after successful surgery. Over the last few years efforts have been directed towards the development of adjuvant therapies in attempts to improve outcome. The main trials of adjuvant chemotherapy, chemoradiotherapy and chemoradiotherapy with follow-on chemotherapy are described in this paper, followed by the results of the ESPAC-1 trial and the status of ESPAC-2 and -3 trials. PMID:18333088

  13. A Phase II Clinical Trial of Concurrent Helical Tomotherapy plus Cetuximab Followed by Adjuvant Chemotherapy with Cisplatin and Docetaxel for Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Xinxin; Du, Lei; Zhao, Feifang; Wang, Qiuju; Yang, Shiming; Ma, Lin

    2016-01-01

    Purpose: The present clinical trial was designed to evaluate the efficacy and safety of concurrent helical tomotherapy (HT) with cetuximab followed by adjuvant chemotherapy with docetaxel and cisplatin (TP) in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Materials and Methods: This phase II clinical trial included 43 patients with Stage III/IV LANC (33 Stage III and 10 Stage IV). The treatment consisted of concurrent HT with cetuximab (400 mg/m2 loading dose and weekly 250mg/m2), followed by four cycles of chemotherapy [docetaxel (70 mg/m2 on Day 1) and cisplatin (40 mg/m2 on Days 1 and 2 every 3 weeks). Side effects were evaluated with CTCAE criteria (Common Terminology Criteria for Adverse Events 3.0). Results: The median follow-up duration was 48.0 months [95% confidence interval (CI) 41.7-58.0 months], the 2-year locoregional failure-free rate (LFFR), progression-free survival (PFS), distant failure-free rate (DFFR) and overall survival (OS) were 95.2%, 79.1%, 88.1% and 93.0% respectively; the 3-year LFFR, DFFR, PFS and OS were 92.7%, 85.6%, 72.0% and 85.7% respectively. The most common grade 3 toxicities were oropharyngeal mucositis (81.4%) and RT-related dermatitis (7.0%). No patients had more than grade 3 radiation related toxicities and no patients required nasogastric feeding. One patient experienced grade 3 osteonecrosis at 18 months after treatment. Conclusions: Concurrent HT with cetuximab followed by adjuvant chemotherapy with TP is an effective strategy for the treatment of LANC with encouraging survival rates and minimal side effects. PMID:27019628

  14. Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: 10-Year Follow-Up

    SciTech Connect

    Kim, Tae-Won; Lee, Je-Hwan; Lee, Jung-Hee; Ahn, Jin-Hee; Kang, Yoon-Koo; Lee, Kyoo-Hyung; Yu, Chang-Sik; Kim, Jong-Hoon; Ahn, Seung-Do; Kim, Woo-Kun; Kim, Jin-Cheon; Lee, Jung-Shin

    2011-11-15

    Purpose: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. Methods and Materials: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m{sup 2}/day and leucovorin 20 mg/m{sup 2}/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. Results: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). Conclusions: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

  15. Changes over time in the impact of gene-expression profiles on the administration of adjuvant chemotherapy in estrogen receptor positive early stage breast cancer patients: A nationwide study.

    PubMed

    Kuijer, A; Drukker, C A; Elias, S G; Smorenburg, C H; Th Rutgers, E J; Siesling, S; van Dalen, Th

    2016-08-15

    Ten years ago gene-expression profiles were introduced to aid adjuvant chemotherapy decision making in breast cancer. Since then subsequent national guidelines gradually expanded the indication area for adjuvant chemotherapy. In this nation-wide study the evolution of the proportion of patients with estrogen-receptor positive (ER+) tumors receiving adjuvant chemotherapy in relation to gene-expression profile use in patient groups that became newly eligible for chemotherapy according to national guideline changes over time is assessed. Data on all surgically treated early breast cancer patients diagnosed between 2004-2006 and 2012-2014 were obtained from the Netherlands Cancer Registry. ER+/Her2- patients with tumor-characteristics making them eligible for gene-expression testing in both cohorts and a discordant chemotherapy recommendation over time (2004 guideline not recommending and 2012 guideline recommending chemotherapy) were identified. We identified 3,864 patients eligible for gene-expression profile use during both periods. Gene-expression profiles were deployed in 5% and 35% of the patients in the respective periods. In both periods the majority of patients was assigned to a low genomic risk-profile (67% and 69%, respectively) and high adherence rates to the test result were observed (86% and 91%, respectively). Without deploying a gene-expression profile 8% and 52% (p <0.001) of the respective cohorts received chemotherapy while 21% and 28% of these patients received chemotherapy when a gene-expression profile was used (p 0.191). In conclusion, in ER+/Her2- early stage breast cancer patients gene-expression profile use was associated with a consistent proportion of patients receiving chemotherapy despite an adjusted guideline-based recommendation to administer chemotherapy. PMID:27062369

  16. The Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colorectal Cancer is Independent of Age and Comorbidity

    PubMed Central

    Wildes, Tanya M.; Kallogjeri, Dorina; Powers, Brian; Vlahiotis, Anna; Mutch, Matthew; Spitznagel, Edward L.; Tan, Benjamin; Piccirillo, Jay F.

    2010-01-01

    Objectives To determine the combined effect of age and comorbidity on receipt of chemotherapy and its impact on survival in elderly patients with stage III colorectal cancer (CRC). Materials and methods All patients over age 65 with Stage III CRC diagnosed 1996–2006 were identified from the Barnes-Jewish Hospital Oncology Data Services registry. An age/comorbidity staging system was created using the ACE-27 comorbidity index and data from both Stage II and III CRC. The staging system was then applied to patients with Stage III CRC. Odds of receiving chemotherapy were calculated, and survival analyses determined the impact of chemotherapy on overall survival in each age/comorbidity stage. Results 435 patients with Stage III CRC were evaluated [median age 75 years (range 65–99)]. Advancing age/comorbidity stage (Alpha, Beta, Gamma) was associated with decreasing odds of receiving chemotherapy for Stage III CRC [Odds Ratio 0.83 (95% CI, 0.51–1.35) for Beta and 0.14 (95% CI, 0.08–0.24) for Gamma, compared to Alpha]. Chemotherapy was associated with lower risk of death in each of the age/comorbidity stages, compared to those who underwent surgery only. The hazard ratio for death in patients who did not receive chemotherapy, relative to those who did, within each age/comorbidity stage was 1.8 [95%CI 1.06–3.06] for Alpha, 2.24 [95%CI 1.38–3.63] for Beta and 2.10 [95% CI 1.23–3.57] for Gamma. Conclusion While stage III CRC patients with increasing age and comorbidity are less likely to receive chemotherapy, receipt of chemotherapy is associated with a lower risk of death. PMID:21113435

  17. Feasibility Of Administering Adjuvant Chemotherapy Of Pemetrexed Followed By Pemetrexed/oxaliplatin Immediately Post-VATS In Patients With Completely Resected NSCLC

    PubMed Central

    He, Jianxing; Shao, Wenlong; Li, Shuben; Chen, Manyin; Chen, Hanzhang; Liu, Jun; Wang, Wei; Qiu, Yuan; Wang, Daoyuan

    2009-01-01

    Non-small cell lung cancer (NSCLC) accounts for the largest number of cancer deaths annually, worldwide. It seems reasonable to test a less toxic regimen also in early stages after complete (R0) resection of the tumor, where reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and hence perhaps improve survival. The main purpose of this phase II trial is to evaluate the clinical feasibility-in terms of patients without dose limiting toxicities or premature treatment withdrawal or death-of administering adjuvant chemotherapy of pemetrexed followed by pemetrexed/oxaliplatin immediately post-VATS (video-assisted thoracic surgery) in patients with completely resected NSCLC. PMID:22263005

  18. Trial on Refinement of Early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: The TREAT protocol

    PubMed Central

    Kreuter, Michael; Vansteenkiste, Johan; Griesinger, Frank; Hoffmann, Hans; Dienemann, Hendrik; De Leyn, Paul; Thomas, Michael

    2007-01-01

    Background Adjuvant chemotherapy has been proven to be beneficial for patients with early stage non-small cell lung cancer. However, toxicity and insufficient dose delivery have been critical issues with the chemotherapy used. Doublet regimens with pemetrexed, a multi-target folate inhibitor, and platin show clear activity in non-small cell lung cancer and are well tolerated with low toxicity rates and excellent delivery. Methods/Design In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms. Discussion The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival. Trial Registration Clinicaltrials.gov NCT00349089 PMID:17488518

  19. A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers who receive adjuvant chemotherapy following surgery.

    PubMed

    Park, Yeon Hee; Jung, Hae Hyun; Do, In-Gu; Cho, Eun Yoon; Sohn, Insuk; Jung, Sin-Ho; Kil, Won Ho; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck

    2015-04-15

    The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63 and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis and were validated with cross-validation. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% [95% confidence interval (CI), 48.6-78.9%] and 85% (95% CI, 79.2-90.7%), respectively. When adjusting for TNM stage, the distant recurrence-free survival (DRFS)s in the low-risk group was significantly longer than that in the high-risk group (p <0.001) for early stage (I and II) and advanced stage (III) tumors. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy. PMID:25537444

  20. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  1. Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision.

    PubMed

    Kainthla, Radhika; Huerta, Sergio

    2016-10-01

    The management of adenocarcinoma of the rectum is a dynamic field in oncology. The multidisciplinary approach to the management of this disease continues to evolve in each segment of its trimodality treatment. New scheduling regimens and radiosensitizing agents continue to emerge. Although total mesorectal excision continues to be the operation of choice for rectal cancers, what is done before and after surgery continues to evolve to maximize an ideal oncologic outcome with minimal morbidity. The achievement of a pathological complete response [pCR (i.e. ypT0N0)] in a fraction of patients undergoing neoadjuvant chemoradiation poses an interesting management dilemma. The cohort of patients who can achieve a pCR have superior oncologic outcomes compared to nonresponders. The present review addresses the need for adjuvant therapy in patients with a pCR. We discuss the evolution of the role of adjuvant therapy in patients with rectal cancer and the studies addressing the elimination of this strategy in all patients with rectal cancer with a goal of determining the current evidence that might result in the omission of adjuvant therapy for patients with ypT0N0 rectal cancer after chemoradiation and total mesorectal excision. PMID:27387144

  2. Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.

    PubMed

    Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

    2016-04-01

    Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26-55 years) and the median duration of follow-up was 64 months (range, 28-100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis. PMID:27057900

  3. LINE-1 Methylation Status Correlates Significantly to Post-Therapeutic Recurrence in Stage III Colon Cancer Patients Receiving FOLFOX-4 Adjuvant Chemotherapy

    PubMed Central

    Fan, Yun-Ching; Chang, Wei-Chiao; Lu, Chien-Yu; Wu, I-Chen; Hsu, Wen-Hung; Huang, Ching-Wen; Wang, Jaw-Yuan

    2015-01-01

    Background Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients. Materials and Methods 129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes. Results The LINE-1 methylation of all 129 patients was measured on a 0–100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7

  4. Sprouty2 protein in prediction of post-treatment ascites in epithelial ovarian cancer treated with adjuvant carbotaxol chemotherapy

    PubMed Central

    Masoumi-Moghaddam, Samar; Amini, Afshin; Wei, Ai-Qun; Robertson, Gregory; Morris, David L

    2015-01-01

    Ascites development and resistance to chemotherapy with carbotaxol are common clinical problems in epithelial ovarian cancer, partly due to the activation of MAPK/ERK signaling. Sprouty proteins are negative modulators of MAPK/ERK pathway, but their role in predicting resistance to carbotaxol chemotherapy and ascites development is unknown. In this study, we evaluated the expression of Sprouty protein isoforms by immunohistochemistry. The associations between the Sprouty expression and the clinicopathological features, including chemoresistance and the presence of ascites, were then explored. We found that the decreased expression of Spry2 was correlated with the post-treatment development of ascites and represented an independent predictor of this condition in carbotaxol-treated patients. However, no association was observed between the Sprouty expression and chemoresistance. In conclusion, our results suggest that Spry2 may be useful for patient follow-up and monitoring as it predicts the development of ascites in epithelial ovarian cancer cases treated with carbotaxol. PMID:26396926

  5. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    PubMed Central

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  6. Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) Study

    PubMed Central

    Alexopoulou, Zoi; Kalogeras, Konstantine T.; Zagouri, Flora; Timotheadou, Eleni; Gogas, Helen; Pentheroudakis, George; Christodoulou, Christos; Koutras, Angelos; Bafaloukos, Dimitrios; Aravantinos, Gerasimos; Papakostas, Pavlos; Charalambous, Elpida; Papadopoulou, Kyriaki; Varthalitis, Ioannis; Efstratiou, Ioannis; Zaramboukas, Thomas; Patsea, Helen; Scopa, Chrisoula D.; Skondra, Maria; Kosmidis, Paris; Pectasides, Dimitrios; Fountzilas, George

    2015-01-01

    Background The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9) and kinase (exon 20) domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signaling in patients with early breast cancer. Methods Tumor tissue samples from 1008 early breast cancer patients treated with adjuvant chemotherapy in two similar randomized trials of HeCOG were examined. Tumors were subtyped with immunohistochemistry (IHC) and FISH for ER, PgR, Ki67, HER2 and androgen receptor (AR). PIK3CA mutations were analyzed by Sanger sequencing (exon 20) and qPCR (exon 9) (Sanger/qPCR mutations). In 610 cases, next generation sequencing (NGS) PIK3CA mutation data were also available. PIK3CA mutations and PTEN protein expression (IHC) were analyzed in luminal tumors (ER and/or PgR positive), molecular apocrine carcinomas (MAC; ER/PgR negative / AR positive) and hormone receptor (ER/PgR/AR) negative tumors. Results PIK3CA mutations were detected in 235/1008 tumors (23%) with Sanger/qPCR and in 149/610 tumors (24%) with NGS. Concordance between the two methods was good with a Kappa coefficient of 0.76 (95% CI 0.69–0.82). Lobular histology, low tumor grade and luminal A tumors were associated with helical domain mutations (PIK3CAhel), while luminal B with kinase domain mutations (PIK3CAkin). The overall incidence of PIK3CA mutations was higher in luminal as compared to MAC and hormone receptor negative tumors (p = 0.004). Disease-free and overall survival did not significantly differ with respect to PIK3CA mutation presence and type. However, a statistically significant interaction between PIK3CA mutation status and PTEN low protein expression with regard to prognosis was identified. Conclusions The present study did not show any prognostic significance of specific PIK3CA mutations in a large group of

  7. Radiofrequency Ablation–Induced Upregulation of Hypoxia-Inducible Factor-1α Can Be Suppressed with Adjuvant Bortezomib or Liposomal Chemotherapy

    PubMed Central

    Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir; Ahmed, Muneeb

    2014-01-01

    successfully suppressed with an adjuvant HIF-1α-specific inhibitor, bortezomib, or non–HIF-1α-specific liposomal chemotherapy. PMID:25439675

  8. The role of induction and adjuvant chemotherapy in combination with concurrent chemoradiotherapy for nasopharyngeal cancer: a Bayesian network meta-analysis of published randomized controlled trials

    PubMed Central

    Yu, Hongliang; Gu, Dayong; He, Xia; Gao, Xianshu; Bian, Xiuhua

    2016-01-01

    Whether the addition of induction chemotherapy (IC) or adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locally advanced nasopharyngeal cancer is unknown. A Bayesian network meta-analysis was performed to investigate the efficacy of CCRT, IC + CCRT, and CCRT + AC on locally advanced nasopharyngeal cancer. The overall survival (OS) with hazard ratios (HRs) and locoregional recurrence rates (LRRs) and distant metastasis rates (DMRs) with risk ratios (RRs) were investigated. After a comprehensive database search, eleven studies involving 2,626 assigned patients were included in this network meta-analysis. Compared with CCRT alone, IC + CCRT resulted in no significant improvement in OS or LRR and a marginal improvement in DMR (OS: HR =0.67, 95% credible interval (CrI) 0.32–1.18; LRR: RR =1.79, 95% CrI 0.80–3.51; DMR: RR =1.79, 95% CrI 0.24–1.04) and CCRT + AC exhibited no beneficial effects on any of the endpoints of OS, LRR, or DMR (OS: HR =0.99, 95% CrI 0.64–1.43; LRR: RR =0.78, 95% CrI 0.43–1.32; DMR: RR =0.85, 95% CrI 0.57–1.24). As a conclusion, for locally advanced nasopharyngeal cancer, no significant differences in the treatment efficacies of CCRT, IC + CCRT, and CCRT + AC were found, with the exception of a marginally significant improvement in distant control observed following IC + CCRT compared with CCRT alone. PMID:26793000

  9. A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy

    PubMed Central

    Griffin, L.; Balcueva, E. P.; Groteluschen, D. L.; Samuel, T. A.; Lesser, G. J.; Naughton, M. J.; Case, L. D.; Shaw, E. G.; Rapp, S. R.

    2016-01-01

    Purpose Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Methods Women who received adjuvant chemotherapy 1–5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Results Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory—the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p=0.033) and HVLT-R Discrimination (p=0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Conclusion Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Implications for Cancer Survivors Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results. PMID:26130292

  10. Feasibility of adjuvant chemotherapy with S-1 consisting of a 4-week administration and a two-week rest period in patients with completely resected non-small cell lung cancer

    PubMed Central

    OKUMURA, SHUNSUKE; SASAKI, TAKAAKI; SATOH, KAZUHIRO; KITADA, MASAHIRO; NAGASE, ATSUSHI; YATSUYANAGI, EIJI; OHSAKI, YOSHINOBU

    2013-01-01

    The efficacy of adjuvant chemotherapy with S-1 in patients with completely resected non-small cell lung cancer (NSCLC) has yet to be clarified, and the appropriate schedule for the adjuvant chemotherapy with S-1 remains unknown. A phase II study was conducted to evaluate the feasibility and efficacy of adjuvant chemotherapy with S-1. Patients enrolled in this study were 20–75 years old, had pathological stage IB-IIIA NSCLC, and had received complete resection of NSCLC. S-1 (80 mg/m2) was administered orally to the patients for four weeks followed by a two-week rest period (conventional schedule), for a maximum of eight cycles. The primary endpoint was relative dose intensity (RDI), while the secondary endpoints were safety and 1 year of disease-free survival (1y-DFS). Between May 2007 and October 2009, 28 patients were enrolled. The RDI was 63.1% (95% CI, 48.6–77.7). No grade 3 or worse hematological toxicity was observed. Grade 3 non-hematological toxicities were observed in four patients. No grade 4 or worse hematological toxicity was detected. The probability of 1y-DFS was 85.7% (95% CI, 72.8–98.6). In the subgroup analysis, the median RDI of patients over 65 years old was lower compared to the other patients (44.8 vs. 100%; P=0.013; Mann-Whitney U test). Creatinine clearance (CCr) was lower in the older group, with more grade 2 or 3 non-hematological toxicities in the elderly patients. These results suggest that the conventional schedule of adjuvant chemotherapy with S-1 is not likely to be feasible in older patients with completely resected NSCLC. PMID:24649134

  11. Feasibility and toxicity of adjuvant chemotherapy using S-1 granules for local advanced squamous cell carcinoma of the head and neck.

    PubMed

    Suzuki, Shinsuke; Honda, Kohei; Sato, Teruyuki; Yamazaki, Kazuharu; Ishikawa, Kazuo

    2015-10-01

    S-1 granulated powder has recently been released to the market as an additional format to that of the capsule. Patients who previously found it difficult to swallow the capsules are now able to take S-1 in powder form. This study evaluated the feasibility of S-1 granulated powder as adjuvant chemotherapy for advanced head and neck cancer. S-1 was orally administered for 2  weeks, followed by 1  week of rest (one course) for 12  months (16 courses). Twenty-four stage III and IV head and neck cancer patients were enrolled in this study. In total, 10 (47.6%) of the patients follow the planned schedule and dose. Severe adverse events were observed in 22 patients (91.7%), whereas no grade 4 adverse events were observed. S-1 granulated powder should be presented as an additional option for the treatment of head and neck cancer, especially for patients experiencing difficulty in swallowing oral medications. PMID:25971448

  12. Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest

    PubMed Central

    YAMATSUJI, TOMOKI; FUJIWARA, YASUHIRO; MATSUMOTO, HIDEO; HATO, SHINJI; NAMIKAWA, TSUTOMU; HANAZAKI, KAZUHIRO; TAKAOKA, MUNENORI; HAYASHI, JIRO; SHIGEMITSU, KAORI; YOSHIDA, KAZUHIRO; URAKAMI, ATSUSHI; UNO, FUTOSHI; NISHIZAKI, MASAHIKO; KAGAWA, SHUNSUKE; NINOMIYA, MOTOKI; FUJIWARA, TOSHIYOSHI; HIRAI, TOSHIHIRO; NAKAMURA, MASAFUMI; HAISA, MINORU; NAOMOTO, YOSHIO

    2015-01-01

    In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID:26137261

  13. MCL-1 is the key target of adjuvant chemotherapy to reverse the cisplatin-resistance in NSCLC.

    PubMed

    Ma, Jun; Zhao, Zhenxian; Wu, Kaiming; Xu, Zhe; Liu, Kuanzhi

    2016-08-10

    Cisplatin is one of the most effective chemotherapeutic agents for the treatment of lung cancer. However, the acquired resistance occurred in cancer cells limits the clinical application of cisplatin. MCL-1, which is an important member in the pro-survival Bcl-2 family, plays a critical role in multidrug resistance (MDR). The aim of the present study is to investigate the value of Pan-Bcl-2 inhibitor as sensitizer for the chemotherapy of cisplatin-resistant non-small cell lung cancer (NSCLC) cells. We found the obatoclax but not the ABT-737 significantly decreased the IC50 (half maximal inhibitory concentration) of cisplatin in cisplatin-resistant NSCLC cells. Furthermore, we demonstrated that the mechanism of obatoclax-promoted cell death induced by cisplatin was dependent on the inhibition of MCL-1, which couldn't be inhibited by ABT-737 but is the target of obatoclax. Moreover, inhibition of MCL-1 recovered the function of NOXA and BAK in cisplatin-resistant NSCLC cells, leading to the promotion of mitochondrial apoptosis induced by cisplatin. Interestingly, our date indicated the obatoclax also reversed the cross-resistance in cisplatin-resistant NSCLC cells. Therefore, we demonstrated that the targeted therapy with MCL-1 inhibitors, such as obatoclax, may represent a novel strategy for cancer therapy. PMID:27138804

  14. Gemcitabine and cisplatin as neo-adjuvant chemotherapy for non-small cell lung cancer: a phase II study.

    PubMed

    Aydiner, Adnan; Kiyik, Murat; Cikrikcioglu, Saadettin; Kosar, Filiz; Gurses, Atilla; Turna, Akif; Yazar, Aziz; Dilege, Sukru; Goksel, Tuncay; Cakan, Alpaslan

    2007-11-01

    The combination of gemcitabine and cisplatin is one of the most active chemotherapy regimens against non-small cell lung cancer (NSCLC). This study was designed to evaluate the efficacy and safety of gemcitabine combined with cisplatin in a 3-week cycle regimen for patients with operable, early stage NSCLC. Gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8 of each 21-day cycle for 3 cycles, followed by cisplatin at a dose of 75 mg/m(2) on day 1 was administered to patients with previously untreated, operable, early stage (IB-IIIA) NSCLC. A total of 47 patients (46 male, mean age 56.0+/-8.0 years) who met the eligibility criteria were enrolled. The pathological complete response rate was 5.3% of operated patients and 4.3% of total patients. At visit 4, 57.1% of the patients had partial response, 38.1%, stable disease and 4.8%, progressive disease. The main toxicities - leukopenia, neutropenia and thrombocytopenia - were usually clinically asymptomatic and did not require hospitalization. Non-hematological toxicities were minimal and manageable. Disease free and 12-month overall survival rates were over 70% and 80%, respectively. This study demonstrates that the administration of gemcitabine and cisplatin combination for 3 cycles is effective and tolerable for patients with operable, early stage NSCLC. Low toxicity profile and promising survival outcome suggest that this regimen has an encouraging activity in this subset of patients. PMID:17683827

  15. Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

    PubMed

    Fernanda Amary, M; Ye, Hongtao; Berisha, Fitim; Khatri, Bhavisha; Forbes, Georgina; Lehovsky, Katie; Frezza, Anna M; Behjati, Sam; Tarpey, Patrick; Pillay, Nischalan; Campbell, Peter J; Tirabosco, Roberto; Presneau, Nadège; Strauss, Sandra J; Flanagan, Adrienne M

    2014-08-01

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors. PMID:24861215

  16. Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy

    PubMed Central

    Fernanda Amary, M; Ye, Hongtao; Berisha, Fitim; Khatri, Bhavisha; Forbes, Georgina; Lehovsky, Katie; Frezza, Anna M; Behjati, Sam; Tarpey, Patrick; Pillay, Nischalan; Campbell, Peter J; Tirabosco, Roberto; Presneau, Nadège; Strauss, Sandra J; Flanagan, Adrienne M

    2014-01-01

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors. PMID:24861215

  17. Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Gandola, Lorenza; Spreafico, Filippo; Luksch, Roberto; Collini, Paola; Giangaspero, Felice; Simonetti, Fabio; Casanova, Michela; Cefalo, Graziella; Pignoli, Emanuele; Ferrari, Andrea; Terenziani, Monica; Podda, Marta; Meazza, Cristina; Polastri, Daniela; Poggi, Geraldina; Ravagnani, Fernando; Fossati-Bellani, Franca

    2006-03-15

    Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.

  18. Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue

    PubMed Central

    2010-01-01

    Background Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs. Methods This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up. Discussion This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy. Trial registration This study is registered at the Netherlands Trial

  19. Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients

    PubMed Central

    Chen, Jin-Hua; Yen, Yu-Chun; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Lin, Ming-Chin; Wu, Szu-Yuan

    2016-01-01

    Abstract The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age <20 years, missing sex data, docetaxel use during or after RT, induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose <7000 cGy, curative head and neck cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence. We enrolled 10,721 stage III–IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum-based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22–1.53) and 1.44 (1.36–1.52) in arms 2 and 3, respectively. In a

  20. Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

    PubMed Central

    Swain, Sandra M.; Tang, Gong; Geyer, Charles E.; Rastogi, Priya; Atkins, James N.; Donnellan, Paul P.; Fehrenbacher, Louis; Azar, Catherine A.; Robidoux, André; Polikoff, Jonathan A.; Brufsky, Adam M.; Biggs, David D.; Levine, Edward A.; Zapas, John L.; Provencher, Louise; Northfelt, Donald W.; Paik, Soonmyung; Costantino, Joseph P.; Mamounas, Eleftherios P.; Wolmark, Norman

    2013-01-01

    Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed. PMID:23940225

  1. Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy.

    PubMed

    Chanat, Cédric; Delbaldo, Catherine; Denis, Jennifer; Bocaccio, François; Cojean-Zelek, Isabelle; Le Guyader, Nathalie

    2015-10-01

    Docetaxel is an antineoplastic drug from the taxane family that inhibits tubulin polymerization. Its brand name is Taxotere. In mid-2010, the formulation of Taxotere changed from a two-vial preparation needing a predilution (T2V) to a one-vial ready-to-use preparation (T1V). The aim of this study was to compare the toxicity profile of these two formulations. This retrospective observational and monocentric study included all patients who received Taxotere-based chemotherapy (100 mg/m) as an adjuvant or a neoadjuvant treatment for localized breast cancer, following initial treatment with anthracycline-based chemotherapy. Patients received either T2V or T1V Taxotere depending on the period of treatment. The main endpoint was the ratio of the dose of Taxotere received to that scheduled (R=docetaxel dose received/docetaxel dose scheduled). The secondary endpoint was tolerance. A total of 97 patients were included: 39 in the T2V group and 58 in the T1V group. The ratio of docetaxel received/docetaxel scheduled was significantly lower in the T1V than in the T2V group (0.83 vs. 0.95, respectively; P=0.028). A higher proportion of patients did not receive the totality of the scheduled dose in the T1V than in the T2V group (28 vs. 8%, respectively; P=0.03). Furthermore, the proportion of patients experiencing cutaneous toxicity was significantly higher in the T1V than in the T2V group (50 vs. 15%, respectively; P<0.001) as well as for neurological toxicity (31 vs. 15%, respectively; P=0.03). The frequency of grade 3 toxicities was higher in the T1V than in the T2V group (50 vs. 8%, P=0.016). The frequency of idiosyncratic toxicities was not affected by the change of formulation (4.7 vs. 5.4%, P=0.98). This study shows that patients treated with the T1V formulation received a significantly smaller dose of Taxotere than patients treated with T2V. In this small retrospective study, no conclusions can be drawn as to why a change in formulation would be associated with

  2. Benefit of Adjuvant Chemotherapy and Pelvic Lymph Node Dissection in pT3 and Node Positive Bladder Cancer Patients Treated with Radical Cystectomy

    PubMed Central

    Boström, Peter J.; Mirtti, Tuomas; van Rhijn, Bas; Fleshner, Neil E.; Finelli, Antonio; Laato, Matti; Jewett, Michael A.; Moore, Malcom J.; Sridhar, Srikala; Nurmi, Martti; Tannock, Ian F.; Zlotta, Alexandre R.

    2016-01-01

    Background: Benefits of adjuvant chemotherapy (AC) and extent of pelvic lymph node dissection (PLND) in radical cystectomy (RC) are debated. Results from randomized trials are still expected. Objective: To analyze the effects of AC and PLND in two academic centers with opposite policies regarding their use. Methods: 581 bladder cancer patients who underwent RC without neoadjuvant chemotherapy, from Toronto (University Health Network), Canada, and Turku University Hospital, Finland were included. Disease specific survival (DSS) and failure patterns were assessed. Results: Centers differed in PLND rate (93% and 36% in Toronto and Turku respectively, p <  0.001), PLND extent (≥10 removed nodes, 58% vs. 8%, p <  0.001) and AC rate (21% vs. 2%, p <  0.001). Survival between centers among pT≤1 or pT4 patients was similar. pT3 patients in Toronto had an improved 10 year DSS (43% vs. 22%, p = 0.025). Distant failures were less common after AC (HR 0.56, 95%  CI 0.33–0.98, p <  0.042). In node positive (N+) patients, mortality was significantly higher in Turku (HR 2.19, 95%  CI 1.44–3.34, p <  0.001) and lower in patients receiving AC (HR 0.60, 95%  CI 0.37–0.99, p = 0.044). 41% DSS at 10 years was observed in N+ Toronto patients. Limitations included the non-randomized retrospective design and absence of propensity score analysis. Conclusion: Combining AC and PLND to RC is associated with improved survival in pT3 and N+ patients. PLND did not affect survival independently but helps in selecting patients for AC. Our data adds to the growing body of evidence supporting the usefulness of AC in addition to PLND in high risk patients operated by cystectomy. PMID:27376145

  3. Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial?

    PubMed Central

    2013-01-01

    Introduction Predictive cancer biomarkers to guide the right treatment to the right patient at the right time are strongly needed. The purpose of the present study was to validate prior results that tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or in combination with either HER2 or TOP2A copy number can be used to predict benefit from epirubicin (E) containing chemotherapy compared with cyclophosphamide, methotrexate and fluorouracil (CMF) treatment. Methods For the purpose of this study, formalin fixed paraffin embedded tumor tissue from women recruited into the BR9601 clinical trial, which randomized patients to E-CMF versus CMF, were analyzed for TIMP-1 immunoreactivity. Using previously collected data for HER2 amplification and TOP2A gene aberrations, we defined patients as "anthracycline non-responsive", that is, 2T (TIMP-1 immunoreactive and TOP2A normal) and HT (TIMP-1 immunoreactive and HER2 negative) and anthracycline responsive (all other cases). Results In total, 288 tumors were available for TIMP-1 analysis with (183/274) 66.8%, and (181/274) 66.0% being classed as 2T and HT responsive, respectively. TIMP-1 was neither associated with patient prognosis (relapse free survival or overall survival) nor with a differential effect of E-CMF and CMF. Also, TIMP-1 did not add to the predictive value of HER2, TOP2A gene aberrations, or to Ki67 immunoreactivity. Conclusion This study could not confirm the predictive value of TIMP-1 immunoreactivity in patients randomized to receive E-CMF versus CMF as adjuvant treatment for primary breast cancer. PMID:23570501

  4. Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy

    PubMed Central

    Odin, Elisabeth; Sondén, Arvid; Gustavsson, Bengt; Carlsson, Göran; Wettergren, Yvonne

    2015-01-01

    Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3 to 5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p < 0.001 and p < 0.01, respectively) with a decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in the transport of folates into the cells and each functions optimally at a different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin. PMID:26193446

  5. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  6. Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy.

    PubMed

    Odin, Elisabeth; Sondén, Arvid; Gustavsson, Bengt; Carlsson, Göran; Wettergren, Yvonne

    2015-01-01

    Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3 to 5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p < 0.001 and p < 0.01, respectively) with a decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in the transport of folates into the cells and each functions optimally at a different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin. PMID:26193446

  7. Adjuvant high-dose chemotherapy with autologous hematopoietic stem cell support for high-risk primary breast cancer: results from the Italian national registry.

    PubMed

    Pedrazzoli, Paolo; Martinelli, Giovanni; Gianni, Alessandro Massimo; Da Prada, Gian Antonio; Ballestrero, Alberto; Rosti, Giovanni; Frassineti, Giovanni Luca; Aieta, Michele; Secondino, Simona; Cinieri, Saverio; Fedele, Roberta; Bengala, Carmelo; Bregni, Marco; Grasso, Donatella; De Giorgi, Ugo; Lanza, Francesco; Castagna, Luca; Bruno, Barbara; Martino, Massimo

    2014-04-01

    The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients has been an area of intense controversy among the medical oncology community. The aim of this study was to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary BC patients who underwent AHPCT in Italy. A total of 1183 patients receiving HDC for high-risk BC (HRBC) (>3 positive nodes) were identified in the Italian registry. The median age was 46 years, 62% of patients were premenopausal at treatment, 60.1% had endocrine-responsive tumors, and 20.7% had a human epidermal growth factor receptor 2 (HER2)-positive tumor. The median number of positive lymph nodes (LN) at surgery was 15, with 71.5% of patients having ≥ 10 positive nodes. Seventy-three percent received an alkylating agent-based HDC as a single procedure, whereas 27% received epirubicin or mitoxantrone-containing HDC, usually within a multitransplantation program. The source of stem cells was peripheral blood in the vast majority of patients. Transplantation-related mortality was .8%, whereas late cardiac and secondary tumor-related mortality were around 1%, overall. With a median follow-up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in patients with endocrine-responsive tumors and in patients receiving multiple transplantation procedures. HER2 status did not affect survival probability. The size of the primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHPCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk primary BC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials. PMID:24374214

  8. Platinum-based drugs: past, present and future.

    PubMed

    Dilruba, Shahana; Kalayda, Ganna V

    2016-06-01

    Platinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of human neoplasms. Their clinical success is, however, limited due to severe side effects and intrinsic or acquired resistance to the treatment. Much effort has been put into the development of new platinum anticancer complexes, but none of them has reached worldwide clinical application so far. Nedaplatin, lobaplatin and heptaplatin received only regional approval. Some new platinum complexes and platinum drug formulations are undergoing clinical trials. Here, we review the main classes of new platinum drug candidates, such as sterically hindered complexes, monofunctional platinum drugs, complexes with biologically active ligands, trans-configured and polynuclear platinum complexes, platinum(IV) prodrugs and platinum-based drug delivery systems. For each class of compounds, a detailed overview of the mechanism of action is given, the cytotoxicity is compared to that of the clinically used platinum drugs, and the clinical perspectives are discussed. A critical analysis of lessons to be learned is presented. Finally, a general outlook regarding future directions in the field of new platinum drugs is given. PMID:26886018

  9. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy.

    PubMed

    Boye, Kjetil; Jacob, Havjin; Frikstad, Kari-Anne M; Nesland, Jahn M; Maelandsmo, Gunhild M; Dahl, Olav; Nesbakken, Arild; Flatmark, Kjersti

    2016-08-01

    Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited. PMID:27273130

  10. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502

    PubMed Central

    Sadahiro, S.; Tsuchiya, T.; Sasaki, K.; Kondo, K.; Katsumata, K.; Nishimura, G.; Kakeji, Y.; Baba, H.; Sato, S.; Koda, K.; Yamaguchi, Y.; Morita, T.; Matsuoka, J.; Usuki, H.; Hamada, C.; Kodaira, S.

    2015-01-01

    Background While adjuvant chemotherapy is preferable for high-risk colon cancer, treatment duration is controversial. Oral uracil and tegafur (UFT)/leucovorin (LV) is widely used as a standard adjuvant chemotherapy for colon cancer in Japan. We conducted a phase III trial to investigate the optimal duration of adjuvant chemotherapy for stage IIB/III colon cancer. Patients and methods Patients with curatively resected stage IIB/III colon cancer were eligible for enrollment in this trial. Patients were registered within 6 weeks after surgery and were randomly assigned to receive UFT/LV for 28 of 35 days for 6 months in the control group or for 5 consecutive days per week for 18 months in the study group. The primary end point was the disease-free survival (DFS), and the secondary end points were overall survival (OS) and safety. Result A total of 1071 patients were registered from 233 centers. A statistically significant difference in DFS was not observed between the study group and the control group; the 5-year DFS was 69% in the study group and 69% in the control group. The 5-year OS was 85% in the study group and 85% in the control group. Conclusion Eighteen-month treatment with UFT/LV did not improve DFS or OS compared with 6-month UFT/LV treatment in patients with stage IIB/III colon cancer. The important finding from this study is that not 18 months but 6 months of treatment is enough for postoperative UFT/LV for stage IIB/III colon cancer. Clinical trial number UMIN-CTR C000000245. PMID:26347106

  11. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    PubMed Central

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  12. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer.

    PubMed

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4-6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  13. CT-Guided Wire Localization for Involved Axillary Lymph Nodes After Neo-adjuvant Chemotherapy in Patients With Initially Node-Positive Breast Cancer.

    PubMed

    Trinh, Long; Miyake, Kanae K; Dirbas, Frederick M; Kothary, Nishita; Horst, Kathleen C; Lipson, Jafi A; Carpenter, Catherine; Thompson, Atalie C; Ikeda, Debra M

    2016-07-01

    Resection of biopsy-proven involved axillary lymph nodes (iALNs) is important to reduce the false-negative rates of sentinel lymph node (SLN) biopsy after neo-adjuvant chemotherapy (NAC) in patients with initially node-positive breast cancer. Preoperative wire localization for iALNs marked with clips placed during biopsy is a technique that may help the removal of iALNs after NAC. However, ultrasound (US)-guided localization is often difficult because the clips cannot always be reliably visible on US. Computed tomography (CT)-guided wire localization can be used; however, to date there have been no reports on CT-guided wire localization for iALNs. The aim of this study was to describe a series of patients who received CT-guided wire localization for iALN removal after NAC and to evaluate the feasibility of this technique. We retrospectively analyzed five women with initially node-positive breast cancer (age, 41-52 years) who were scheduled for SLN biopsy after NAC and received preoperative CT-guided wire localization for iALNs. CT visualized all the clips that were not identified on post-NAC US. The wire tip was deployed beyond or at the target, with the shortest distance between the wire and the index clip ranging from 0 to 2.5 mm. The total procedure time was 21-38 minutes with good patient tolerance and no complications. In four of five cases, CT wire localization aided in identification and resection of iALNs that were not identified with lymphatic mapping. Residual nodal disease was confirmed in two cases: both had residual disease in wire-localized lymph nodes in addition to SLNs. Although further studies with more cases are required, our results suggest that CT-guided wire localization for iALNs is a feasible technique that facilitates identification and removal of the iALNs as part of SLN biopsy after NAC in situations where US localization is unsuccessful. PMID:27061012

  14. The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma-including the analysis of clinicopathological factors influencing relative dose intensity.

    PubMed

    Yabusaki, Norimitsu; Fujii, Tsutomu; Yamada, Suguru; Murotani, Kenta; Sugimoto, Hiroyuki; Kanda, Mitsuro; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

    2016-07-01

    Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated.A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed.Patients with RDIs ≥80% (n = 79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n = 55) (median survival time (MST): 45.6 months, 26.0 months, P < 0.001). Patients with no AC (n = 34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P = 0.79) or in those with <80% (P = 0.73). Patients in the S-1 monotherapy group (n = 49) showed significantly better OS than patients in the gemcitabine monotherapy group (n = 51) (MST: 95.0 months, 26.0 months, respectively; P = 0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P = 0.01), intraoperative blood transfusion (P = 0.005), lymph node metastasis (P = 0.03), and postoperative WBC count (P = 0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P = 0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P = 0.04) as independent predictors of poor RDI.Efforts to

  15. Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment

    PubMed Central

    Al-Khanbashi, Manal; Caramuta, Stefano; Alajmi, Adil M.; Al-Haddabi, Ibrahim; Al-Riyami, Marwa; Lui, Weng-Onn; Al-Moundhri, Mansour S.

    2016-01-01

    Introduction MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. Methods Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant. Results We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis. Conclusion Variations in

  16. West Midlands Oncology Association trials of adjuvant chemotherapy in operable breast cancer: results after a median follow-up of 7 years. I. Patients with involved axillary lymph nodes.

    PubMed Central

    Morrison, J. M.; Howell, A.; Kelly, K. A.; Grieve, R. J.; Monypenny, I. J.; Walker, R. A.; Waterhouse, J. A.

    1989-01-01

    The aim of this study was to test the effectiveness of a regimen of combination chemotherapy known to be active in advanced breast cancer when given as an adjuvant treatment after mastectomy. A total of 569 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after simple mastectomy with axillary sampling, to receive either no adjuvant treatment or intravenous adriamycin 50 mg, vincristine 1 mg, cyclophosphamide 250 mg, methotrexate 150 mg and fluorouracil 250 mg (AVCMF) every 21 days for eight cycles. Randomisation was stratified according to menopausal status and tumour size. Treatment was started within 14 days of surgery in 94% of patients. Eighty-eight per cent of patients received at least seven cycles of chemotherapy with no dose reduction. The median relapse-free survival was prolonged by 14 months in patients treated with AVCMF (chi2 1 = 11.7; P = 0.0006). In the premenopausal group this period was 17 months (chi2 1 = 8.8; P = 0.003) compared with 8 months in the post-menopausal group (chi2 1 = 3.3; P = 0.07). Neither overall survival nor survival in these subgroups was significantly influenced by treatment. PMID:2690913

  17. Nanoscale Drug Delivery Platforms Overcome Platinum-Based Resistance in Cancer Cells Due to Abnormal Membrane Protein Trafficking

    PubMed Central

    Xue, Xue; Hall, Matthew D.; Zhang, Qiang; Wang, Paul C.; Gottesman, Michael M.; Liang, Xing-Jie

    2014-01-01

    The development of cellular resistance to platinum-based chemotherapies is often associated with reduced intracellular platinum concentrations. In some models, this reduction is due to abnormal membrane protein trafficking, resulting in reduced uptake by transporters at the cell surface. Given the central role of platinum drugs in the clinic, it is critical to overcome cisplatin resistance by bypassing the plasma membrane barrier to significantly increase the intracellular cisplatin concentration enough to inhibit the proliferation of cisplatin-resistant cells. Therefore, rational design of appropriate nanoscale drug delivery platforms (nDDPs) loaded with cisplatin or other platinum analogs as payloads is a possible strategy to solve this problem. This review will focus on the known mechanism of membrane trafficking in cisplatin-resistant cells, and the development and employment of nDDPs to improve cell uptake of cisplatin. PMID:24219825

  18. Systemic capillary leak syndrome in a patient receiving adjuvant oxaliplatin for locally advanced colon cancer.

    PubMed

    Anderson, Brandon J; Peterson, Lindsay L

    2016-10-01

    Colorectal cancer is the third most common cancer diagnosed in the USA each year. Oxaliplatin, a platinum-based chemotherapy agent, is part of the standard adjuvant chemotherapy regimen FOLFOX (oxaliplatin with 5-fluorouracil [5-FU] and leucovorin [LV]) for the treatment of stage III and some high-risk stage II colorectal cancers. Although oxaliplatin is generally well tolerated, certain side effects such as nausea, vomiting, and peripheral neuropathy are common. We report a case of oxaliplatin-induced capillary-leak syndrome in a 63-year-old man undergoing his 12th and final cycle of FOLFOX for stage III colorectal cancer. To our knowledge, this is the first case of systemic capillary leak syndrome (SCLS) reported in association with oxaliplatin. Currently, there is no prevention for SCLS. Documenting future cases of SCLS attributed to oxaliplatin is vital, as SCLS is associated with significant morbidity and mortality and no standard treatments beyond supportive care measures exist. Early recognition and diagnosis are therefore essential to improving patient outcomes. PMID:26071595

  19. The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer.

    PubMed

    Annels, Nicola E; Shaw, Victoria E; Gabitass, Rachel F; Billingham, Lucinda; Corrie, Pippa; Eatock, Martin; Valle, Juan; Smith, David; Wadsley, Jonathan; Cunningham, David; Pandha, Hardev; Neoptolemos, John P; Middleton, Gary

    2014-02-01

    In pre-clinical models, the only two chemotherapy drugs which have been demonstrated to directly reduce the number of myeloid-derived suppressor cells (MDSCs) are gemcitabine and 5-fluorouracil. Here we analyze the dynamics of MDSCs, phenotyped as Lin-DR-CD11b+, in patients with advanced pancreatic cancer receiving the combination of gemcitabine and capecitabine, a 5-FU pro-drug. We found no evidence that gemcitabine and capecitabine directly reduce MDSC% in patients. Gemcitabine and capecitabine reduced MDSCs in 42% of patients (n = 19) and MDSC% fell in only 3/9 patients with above-median baseline MDSCs. In 5/8 patients with minimal tumour volume change on treatment, the MDSC% went up: increases in MDSC% in these patients appeared to correlate with sustained cancer-related inflammatory cytokine upregulation. In a separate cohort of 21 patients treated with gemcitabine and capecitabine together with concurrently administered GV1001 vaccine with adjuvant GM-CSF, the MDSC% fell in 18/21 patients and there was a significant difference in the trajectory of MDSCs between those receiving GV1001 and GM-CSF in combination with chemotherapy and those receiving chemotherapy alone. Thus, there was no evidence that the addition of low-dose adjuvant GM-CSF increased Lin-DR-CD11b+ MDSC in patients receiving combination chemoimmunotherapy. 9/21 patients developed an immune response to GV1001 and the MDSCs fell in 8 of these 9 patients, 6 of whom had above-median pre-vaccination MDSC levels. A high pre-vaccination MDSC% does not preclude the development of immunity to a tumour-associated antigen. PMID:24292263

  20. Five-Year Results From a Scandinavian Sarcoma Group Study (SSG XIII) of Adjuvant Chemotherapy Combined With Accelerated Radiotherapy in High-Risk Soft Tissue Sarcoma of Extremities and Trunk Wall

    SciTech Connect

    Jebsen, Nina L.; Bruland, Oyvind S.; Eriksson, Mikael; Engellau, Jacob; Turesson, Ingela; Folin, Annika; Trovik, Clement S.; Hall, Kirsten Sundby

    2011-12-01

    Purpose: To evaluate adjuvant chemotherapy and interpolated accelerated radiotherapy (RT) for adult patients with high-risk soft tissue sarcoma in the extremities or trunk wall. Methods and Materials: High-risk soft tissue sarcoma was defined as high-grade malignancy and at least two of the following criteria: size {>=}8 cm, vascular invasion, or necrosis. Six cycles of doxorubicin and ifosfamide were prescribed for all patients. RT to a total dose of 36 Gy (1.8 Gy twice daily) was inserted between two chemotherapy cycles after marginal margin resection regardless of tumor depth or after wide-margin resection for deep-seated tumors. RT was boosted to 45 Gy in a split-course design in the case of intralesional margin resection. Results: A total of 119 patients were eligible, with a median follow-up of 5 years. The 5-year estimate of the local recurrence, metastasis-free survival, and overall survival rate was 12%, 59%, and 68%, respectively. The group receiving RT to 36 Gy had a local recurrence rate of 10%. In contrast, the local recurrence rate was 29% in the group treated with RT to 45 Gy. The presence of vascular invasion and low chemotherapy dose intensity had a negative effect on metastasis-free and overall survival. Toxicity was moderate after both the chemotherapy and the RT. Conclusions: Accelerated RT interposed between chemotherapy cycles in a selected population of patients with high-risk soft tissue sarcoma resulted in good local and distant disease control, with acceptable treatment-related morbidity. The greater radiation dose administered after intralesional surgery was not sufficient to compensate for the poorer surgical margin. Vascular invasion was the most important prognostic factor for metastasis-free and overall survival.

  1. Oral single-agent chemotherapy in older patients with solid tumours: A position paper from the International Society of Geriatric Oncology (SIOG).

    PubMed

    Biganzoli, L; Lichtman, S; Michel, J-P; Papamichael, D; Quoix, E; Walko, C; Aapro, M

    2015-11-01

    Compared with intravenous (i.v.) chemotherapy, oral administration is convenient, requires fewer healthcare resources, is generally preferred by patients, and may be appropriate in older people with breast, colorectal and lung cancers. The effects of organ dysfunction on drug metabolism and drug interactions in patients with multiple comorbidities must be considered but are not specific to oral chemotherapy. Single-agent oral chemotherapy with capecitabine or vinorelbine is active in older patients with advanced or metastatic breast cancer. Choice of treatment is based mainly on different safety profiles. In the adjuvant treatment of colorectal cancer (CRC), single-agent oral capecitabine is an effective alternative to i.v. fluorouracil (5-FU) regimens. In metastatic CRC, oral, single-agent capecitabine has recently shown encouraging median overall survival in combination with bevacizumab. In non-small cell lung cancer, fit older patients, like their younger counterparts, benefit from platinum-based doublets, with carboplatin preferred to cisplatin. Single agent vinorelbine is an option for those less suited to combination chemotherapy, and oral may be an alternative to i.v. administration. For elderly cancer patients in general, metronomic chemotherapy combines good tolerability with acceptable activity. PMID:26340809

  2. Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study.

    PubMed

    Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

    2015-12-01

    The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10-17) and 31 (28-36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13-22) and an OS of 38 (33-41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20-0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95-9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may

  3. Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study

    PubMed Central

    Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

    2015-01-01

    Abstract The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting. We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma. Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10–17) and 31 (28–36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13–22) and an OS of 38 (33–41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20–0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95–9.77; P < 0.01). We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines

  4. The treatment of soft-tissue sarcomas of the extremities - prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy

    SciTech Connect

    Rosenberg, S.A.; Tepper, J.; Glatstein, E.

    1982-09-01

    Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m/sup 2/), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p/sub 1/ = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (83% and 88% at five years; p/sub 2/ = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p/sub 1/ < 0.00001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p/sub 1/ = 0.00008) and overall survival (95% vs. 74%; p/sub 1/ = 0.04).

  5. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

  6. Exploration of optimal time for initiating adjuvant chemotherapy after surgical resection: A retrospective study in Chinese patients with stage IIIA non‐small cell lung cancer in a single center

    PubMed Central

    Zhu, Yixiang; Zhai, Xiaoyu; Chen, Sipeng

    2016-01-01

    Abstract Background Adjuvant chemotherapy (ACT) can reduce the risk of recurrence and improve survival after surgical resection in non‐small cell lung cancer (NSCLC) patients. We explore the optimal time from surgery to initiation of ACT in Chinese patients with stage IIIA NSCLC. Methods Patients pathologically diagnosed with IIIA NSCLC who underwent radical surgery were included in this study. The cut‐off point of time to initiation of adjuvant chemotherapy (TTAC) was determined by maximally selected log‐rank statistics. Patients were divided into two groups according to the TTAC cut‐off point. Propensity score matching (PSM) was used to eliminate confounding variables, and Kaplan–Meier analysis was used to analyze the impact of TTAC on disease‐free survival (DFS). Results The cut‐off time was 46 days from surgery to the first ACT. Prior to PSM, baseline characteristic variables were balanced with no statistical difference between the groups, except for pathologic subtype and smoking history. No difference in DFS was found between the two groups prior to PSM (P = 0.529); after PSM, the median DFS was consistent between the two (P = 0.822). N2 lymph node station involvement was an independent factor associated with poor survival compared with patients with N0 lymph node involvement. Moderate differentiation and postoperative radiotherapy could improve survival; however, TTAC was not significantly correlated with DFS. Subgroup analyses showed no significant correlation between DFS and different TTAC programs. Conclusion No survival difference was obtained as to when ACT was initiated for patients with stage IIIA NSCLC.

  7. Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial

    PubMed Central

    Pacilio, C; Morabito, A; Nuzzo, F; Gravina, A; Labonia, V; Landi, G; Rossi, E; De Maio, E; Di Maio, M; D'aiuto, G; Botti, G; Normanno, N; Chiodini, P; Gallo, C; Perrone, F; de Matteis, A

    2006-01-01

    The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m−2 (D) with the combination of docetaxel 80 mg m−2 and epirubicin 75 mg m−2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n=26) and D arms (n=25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy. PMID:16622454

  8. RESISTANCE TO PLATINUM-BASED CHEMOTHERAPY IN LUNG CANCER CELL LINES

    PubMed Central

    Chen, Jianli; Emara, Nashwa; Solomides, Charalambos; Parekh, Hemant; Simpkins, Henry

    2010-01-01

    Purpose A series of six lung cancer cell lines of different cell origin (including small cell and mesothelioma) were characterized immunohistochemically and the role of a series of protein candidates previously implicated in drug resistance investigated. Methods These include colony-forming and cell growth assays, immunohistochemistry, siRNA knockouts, Real Time PCR, and Western blots. Results No correlation was found with AKT, HO-1, HO-2, GRP78, 14-3-3zeta and ERCC1 levels and cisplatin nor oxaliplatin cytotoxicity but an association was observed with levels of the enzyme, dihydrodiol dehydrogenase (DDH); an enzyme previously implicated in the development of platinum resistance. The relationship appeared to hold true for those cell lines derived from lung epithelial primary tumors but not for the neuroendocrine/small cell and mesothelioma cell lines. siRNA knockouts to DDH-1 and DDH-2 were prepared with the cell line exhibiting the greatest resistance to cisplatin (A549) resulting in marked decreases in the DDH isoforms as assessed by Real Time PCR, western blot and enzymatic activity. The DDH-1 knockout was far more sensitive to cisplatin than the DDH-2 knockout. Conclusion Thus, sensitivity to cisplatin appeared to be associated with DDH levels in epithelial lung cancer cell lines with the DDH-1 isoform producing the greatest effect. Results in keeping with transfection experiments with ovarian and other cell lines. PMID:20953859

  9. Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial.

    PubMed

    Schmidt, Martina E; Wiskemann, Joachim; Armbrust, Petra; Schneeweiss, Andreas; Ulrich, Cornelia M; Steindorf, Karen

    2015-07-15

    Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group-based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group-based interventions. One-hundred-one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group-based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20-item multidimensional questionnaire, QoL with the EORTC QLQ-C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between-group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p-interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group-based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy. PMID:25484317

  10. The role of surgical margins in treatment of Ewing's sarcoma family tumors: Experience of a single institution with 512 patients treated with adjuvant and neoadjuvant chemotherapy

    SciTech Connect

    Bacci, Gaetano . E-mail: gaetano.bacci@ior.it; Longhi, Alessandra; Briccoli, Antonio; Bertoni, Franco; Versari, Michela; Picci, Piero

    2006-07-01

    Purpose: To evaluate the importance of surgical margins for local and systemic control of Ewing's sarcoma family tumors (ESFT). Methods and Materials: Between 1979 and 1999, 512 patients with ESFTs entered 4 different adjuvant and neoadjuvant studies performed at a single institution. Of these patients, 335 were treated with surgery alone (196) or surgery followed by radiotherapy at doses of 44.8 Gy (139). We compared their outcome with that of the 177 patients who were locally treated by radiotherapy at 60 Gy. Results: Local control (88.8% vs. 80.2%, p < 0.009) and 5-year disease-free survival (63.8% vs. 47.6%, p < 0.0007) were significantly better in patients treated with surgery and, among them, in those with adequate surgical margins (96.6% vs. 71,7%, p < 0.0008, and 69.6% vs. 46.3%, p < 0.0002). Nonetheless, better results were observed only in extremity tumors. Conclusions: Surgery is better than radiotherapy in cases of extremity ESFT with achievable adequate surgical margins, and in cases of inadequate surgical margins, adjuvant reduced-dose radiotherapy is ineffective. Therefore, when inadequate margins are expected, patients are better treated with full-dose radiotherapy from the start.

  11. Esophageal Metastasis to the Iris Effectively Palliated Using Stereotactic Body Radiation Therapy and Adjuvant Intravitreal Chemotherapy: Case Report and Literature Review

    PubMed Central

    Dhakal, Sughosh; Lema, Gareth M.C.; DiLoreto, David A.; Katz, Alan W.

    2012-01-01

    We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris. PMID:23275779

  12. Regorafenib as a potential adjuvant chemotherapy agent in disseminated small colon cancer: Drug selection outcome of a novel screening system using nanoimprinting 3-dimensional culture with HCT116-RFP cells.

    PubMed

    Yoshii, Yukie; Furukawa, Takako; Aoyama, Hironori; Adachi, Naoya; Zhang, Ming-Rong; Wakizaka, Hidekatsu; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2016-04-01

    Colon cancer is one of the leading causes of cancer death worldwide. Adjuvant chemotherapy following primary surgical treatment is suggested to be beneficial in eradicating invisible disseminated small tumors in colon cancer; however, an effective drug remains to be developed. Recently, we reported a novel drug screening system using a nanoimprinting 3-dimensional (3D) culture that creates multicellular spheroids, which simulate in vivo conditions and, thereby, predict effective drugs in vivo. This study aimed to perform drug selection using our recently developed 3D culture system in a human colon cancer HCT116 cell line stably expressing red fluorescent protein (HCT116-RFP), to determine the most effective agent in a selection of clinically used antitumor agents for colon cancer. In addition, we confirmed the efficacy of the selected drug regorafenib, in vivo using a mouse model of disseminated small tumors. HCT116-RFP cells were cultured using a nanoimprinting 3D culture and in vitro drug selection was performed with 8 clinically used drugs [bevacizumab, capecitabine, cetuximab, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, panitumumab and regorafenib]. An in vivo study was performed in mice bearing HCT116-RFP intraperitoneally disseminated small tumors using 3'-[18F]-fluoro-3'-deoxythymidine-positron emission tomography and fluorescence microscopy imaging to evaluate the therapeutic effects. Regorafenib was determined to be the most effective drug in the 3D culture, and significantly inhibited tumor growth in vivo, compared to the untreated control and 5-FU-treated group. The drug 5-FU is commonly used in colon cancer treatment and was used as a reference. Our results demonstrate that regorafenib is a potentially efficacious adjuvant chemotherapeutic agent for the treatment of disseminated small colon cancer and, therefore, warrants further preclinical and clinical studies. PMID:26820693

  13. High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

    PubMed

    Martino, Massimo; Lanza, Francesco; Pavesi, Lorenzo; Öztürk, Mustafa; Blaise, Didier; Leno Núñez, Rubén; Schouten, Harry C; Bosi, Alberto; De Giorgi, Ugo; Generali, Daniele; Rosti, Giovanni; Necchi, Andrea; Ravelli, Andrea; Bengala, Carmelo; Badoglio, Manuela; Pedrazzoli, Paolo; Bregni, Marco

    2016-03-01

    The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials. PMID:26723932

  14. Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

    PubMed Central

    Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-01-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. PMID:25784204

  15. Synergistic effects of laser and adjuvant therapies for cancer: progress in the development of novel cancer treatment methods using combinations of photothermal, photochemical, immunotherapy, and chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Bartels, Kenneth E.; Korbelik, Mladen; Liu, Hong; Nordquist, Robert E.

    2005-04-01

    Combination therapy has been commonly used in chemotherapy, taking advantage of different effects of different chemotherapeutic agents. The treatment effects are often synergistic. The same approach has been investigated in laser phototherapy. Specifically, different combinations of laser photothermal interaction, laser photochemical interaction, immunotherapy and chemotherapy have been used in the treatment of tumors. These novel approaches showed promise in cancer treatment, particularly against metastatic tumors. The recent development in this area is discussed in this paper. Furthermore, a specific combination of photodynamic therapy (PDT) with a novel immunoadjuvant, glycated chitosan (GC), has shown to be effective in the treatment mammary tumors and lung tumors in mice. In the treatment of EMT6 tumor-bearing mice, the Photofrin-based PDT and GC has significantly increased the survival rates from 37.5% with PDT alone to 62.5% when a 0.1-ml 0.5% GC was peritumoral injected immediately after PDT treatment. The survival rate was further increased to 75.0% when GC of higher concentration was used. In comparison, the individual components of the PDT-GC treatment showed either no effect or very limited effects. In the treatment of a poorly immunogenic tumor model, Line 1 lung tumors in mice, the combination of PDT and GC resulted in a 37.5% survival rate, while no survival mice were observed with PDT alone.

  16. Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach.

    PubMed

    Kepka, Lucyna; Socha, Joanna; Rucinska, Monika; Wasilewska-Tesluk, Ewa; Komosinska, Katarzyna

    2016-07-01

    This editorial comments on the study by Lee et al. which reported on the use of postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA-pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients received postoperative chemotherapy (POCT). The five-year overall survival (OS) was significantly higher in patients treated with PORT and POCT than in patients treated with PORT alone. Authors concluded that PORT used as first postoperative strategy does not compromise a benefit of POCT and its implementation should be further studied. We discuss the pros and cons of using PORT before POCT for stage IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however, caution should be paid to not to unnecessarily delay or omit POCT because of its demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could be an attractive approach, but we still have very limited clinical data on its use in this indication. PMID:27501290

  17. Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach

    PubMed Central

    Socha, Joanna; Rucinska, Monika; Wasilewska-Tesluk, Ewa; Komosinska, Katarzyna

    2016-01-01

    This editorial comments on the study by Lee et al. which reported on the use of postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA-pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients received postoperative chemotherapy (POCT). The five-year overall survival (OS) was significantly higher in patients treated with PORT and POCT than in patients treated with PORT alone. Authors concluded that PORT used as first postoperative strategy does not compromise a benefit of POCT and its implementation should be further studied. We discuss the pros and cons of using PORT before POCT for stage IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however, caution should be paid to not to unnecessarily delay or omit POCT because of its demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could be an attractive approach, but we still have very limited clinical data on its use in this indication. PMID:27501290

  18. A Model to Estimate the Risk of Breast Cancer-Related Lymphedema: Combinations of Treatment-Related Factors of the Number of Dissected Axillary Nodes, Adjuvant Chemotherapy, and Radiation Therapy

    SciTech Connect

    Kim, Myungsoo; Kim, Seok Won; Lee, Sung Uk; Lee, Nam Kwon; Jung, So-Youn; Kim, Tae Hyun; Lee, Eun Sook; Kang, Han-Sung; Shin, Kyung Hwan

    2013-07-01

    Purpose: The development of breast cancer-related lymphedema (LE) is closely related to the number of dissected axillary lymph nodes (N-ALNs), chemotherapy, and radiation therapy. In this study, we attempted to estimate the risk of LE based on combinations of these treatment-related factors. Methods and Materials: A total of 772 patients with breast cancer, who underwent primary surgery with axillary lymph node dissection from 2004 to 2009, were retrospectively analyzed. Adjuvant chemotherapy (ACT) was performed in 677 patients (88%). Among patients who received radiation therapy (n=675), 274 (35%) received supraclavicular radiation therapy (SCRT). Results: At a median follow-up of 5.1 years (range, 3.0-8.3 years), 127 patients had developed LE. The overall 5-year cumulative incidence of LE was 17%. Among the 127 affected patients, LE occurred within 2 years after surgery in 97 (76%) and within 3 years in 115 (91%) patients. Multivariate analysis showed that N-ALN (hazard ratio [HR], 2.81; P<.001), ACT (HR, 4.14; P=.048), and SCRT (HR, 3.24; P<.001) were independent risk factors for LE. The total number of risk factors correlated well with the incidence of LE. Patients with no risk or 1 risk factor showed a significantly lower 5-year probability of LE (3%) than patients with 2 (19%) or 3 risk factors (38%) (P<.001). Conclusions: The risk factors associated with LE were N-ALN, ACT, and SCRT. A simple model using combinations of these factors may help clinicians predict the risk of LE.

  19. Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.

    PubMed

    Ogawa, Masaichi; Watanabe, Michiaki; Mitsuyama, Yoshinobu; Anan, Tadashi; Ohkuma, Masahisa; Kobayashi, Tetsuya; Eto, Ken; Yanaga, Katsuhiko

    2014-12-01

    The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer. PMID:25364408

  20. Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy.

    PubMed

    Antonângelo, Leila; Tuma, Taila; Fabro, Alexandre; Acencio, Milena; Terra, Ricardo; Parra, Edwin; Vargas, Francisco; Takagaki, Teresa; Capelozzi, Vera

    2016-06-01

    Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC. PMID:26869608

  1. Aprepitant as prophylaxis of chemotherapy-induced nausea and vomiting in anthracyclines and cyclophosphamide-based regimen for adjuvant breast cancer.

    PubMed

    Meattini, Icro; Francolini, Giulio; Scotti, Vieri; De Luca Cardillo, Carla; Cappelli, Sabrina; Meacci, Fiammetta; Furfaro, Ilaria Francesca; Muntoni, Cristina; Scoccianti, Silvia; Detti, Beatrice; Mangoni, Monica; Nori, Jacopo; Orzalesi, Lorenzo; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2015-03-01

    The aim of our study was to evaluate the efficacy and safety of a three-drug antiemetic prophylaxis in a single-center series treated with anthracyclines and cyclophosphamide-based regimen for BC. We collected data from 92 consecutive patients treated with routine antiemetic prophylaxis consisted of aprepitant (oral 125 mg, on day 1; oral 80 mg, on days 2 and 3), a 5-HT3 receptor antagonist (palonosetron iv 0.25 mg, on day 1), and dexamethasone (iv 12 mg, on day 1). Acute and delayed phases were defined as the first 24 h and days 2-5 after treatment, respectively. Therapy outcomes were defined as complete response (CR), in case of no vomiting, no rescue treatment; complete protection (CP), in case of no vomiting, no rescue treatment, no significant nausea; and total control (TC), in case of no vomiting, no rescue treatment, no nausea. Overall, 89.1 and 81.5% of patients showed CR in acute and delayed phase, respectively; 67.4 and 62% showed CP in acute and delayed phase, respectively; and 52.2 and 48.9% of patients showed TC in acute and delayed phase, respectively. 4.3% complained an episode of emesis during the first 24 h from treatment, while in delayed phase, only 2.2% of patients had vomiting. Our analysis confirmed that a three-drug prophylaxis is safe, effective, and consequently highly recommended in patients who undergo anthracyclines and cyclophosphamide-based regimens, though still not classified as highly emetogenic chemotherapy by all the international guidelines. PMID:25698536

  2. Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity.

    PubMed

    Chen, Juan; Wu, Lin; Wang, Ying; Yin, Jiye; Li, Xiangping; Wang, Zhan; Li, Huihua; Zou, Ting; Qian, Chenyue; Li, Chuntian; Zhang, Wei; Zhou, Honghao; Liu, Zhaoqian

    2016-02-01

    Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients. PMID:26358256

  3. Adjuvant treatment for pancreatic cancer.

    PubMed

    Daoud, Vladimir; Saif, Muhammad Wasif; Goodman, Martin

    2014-07-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women. Surgical resection has been shown to be the only curable treatment available. Unfortunately only 20% of all patients diagnosed with pancreatic cancer are surgical candidates due to the aggressive biology of this disease. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. The survival of these patients, even status post resection and adjuvant therapy, remains poor and therefore the need for alternative adjuvant therapies is needed. We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this paper which are relevant to the issues described above. PMID:25076340

  4. Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704-A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients With Resected Adenocarcinoma of the Pancreas

    SciTech Connect

    Abrams, Ross A.; Winter, Kathryn A.; Regine, William F.; Safran, Howard; Hoffman, John P.; Lustig, Robert; Konski, Andre A.; Benson, Al B.; Macdonald, John S.; Rich, Tyvin A.; Willett, Christopher G.

    2012-02-01

    Purpose: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.

  5. Impact of Lymph Node Ratio on Oncologic Outcomes in ypStage III Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy followed by Total Mesorectal Excision, and Postoperative Adjuvant Chemotherapy

    PubMed Central

    Kim, Jae-Sung; Kim, Kyubo; Chie, Eui Kyu; Kang, Sung-Bum; Lee, Keun-Wook; Kim, Jee Hyun; Jeong, Seung-Yong; Kim, Tae-You

    2015-01-01

    Purpose To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT). Materials and Methods We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study. Results The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02–1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831). Conclusions For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients. PMID:26381522

  6. Prognostic Value of Log Odds of Positive Lymph Nodes after Radical Surgery Followed by Adjuvant Treatment in High-Risk Cervical Cancer

    PubMed Central

    Kwon, Jeanny; Eom, Keun-Yong; Kim, In Ah; Kim, Jae-Sung; Kim, Young-Beom; No, Jae Hong; Kim, Kidong

    2016-01-01

    Purpose The purpose of this study is to compare the prognostic efficacy of the number and location of positive lymph nodes (LN), LN ratio (LNR), and log odds of positive LNs (LODDs) in high-risk cervical cancer treated with radical surgery and adjuvant treatment. Materials and Methods Fifty high-risk patients who underwent radical hysterectomy and pelvic node dissection followed by adjuvant treatment were analyzed retrospectively. The patients had International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIB. Upper LN is defined as common iliac or higher LN, and LNR is the ratio of positive LNs to harvested LNs. LODDs is log odds between positive LNs and negative LNs. Radiotherapy was delivered to the whole pelvis with median 50.4 Gy/28 Fx± to the para-aortic regions. Platinum-based chemotherapy was used in most patients (93%). The median follow-up duration was 80 months. Results The 5-year disease-free survival (DFS) rate was 76.1%, and the overall survival (OS) rate was 86.4%. Treatment failure occurred in 11 patients, and distant failure (DF) was the dominant pattern (90.9%). In univariate analysis, significantly lower DFSwas observed in patients with perineural invasion, ≥ 2 LN metastases, LNR ≥ 10%, upper LN metastasis, and ≥ –1.05 LODDs. In multivariate analysis, ≥ –1.05 LODDs was the only significant factor for DFS (p=0.011). Of patients with LODDs ≥ –1.05, 40.9% experienced DF. LODDs was the only significant prognostic factor for OS as well (p=0.006). Conclusion LODDs ≥ –1.05 was the only significant prognostic factor for both DFS and OS. In patients with LODDs ≥ –1.05, intensified chemotherapy might be required, considering the high rate of DF. PMID:26194370

  7. DNA Repair Pathway Gene Expression Score Correlates with Repair Proficiency and Tumor Sensitivity to Chemotherapy

    PubMed Central

    Pitroda, Sean. P.; Pashtan, Itai. M.; Logan, Hillary. L.; Budke, Brian; Darga, Thomas E.; Weichselbaum, Ralph. R.; Connell, Philip. P.

    2016-01-01

    Homologous recombination (HR) and non-homologous end joining (NHEJ) are alternative pathways of double-strand DNA break repair. We developed a method to quantify the efficiency of DNA repair pathways in the context of cancer therapy. The Recombination Proficiency Score (RPS) utilizes the expression levels for four genes involved in DNA repair pathway preference (RIF1, PARI, RAD51, and Ku80), such that high expression of these genes yields a low RPS. Carcinoma cells with low RPS exhibit HR suppression and frequent DNA copy number alterations, which are characteristic of error-prone repair processes that arise in HR-deficient backgrounds. The RPS system was clinically validated in patients with breast or non-small cell lung carcinomas (NSCLC). Tumors with low RPS were associated with greater mutagenesis, adverse clinical features, and inferior patient survival rates, suggesting that HR suppression plays a central role in promoting the genomic instability that fuels malignant progression. This adverse prognosis associated with low RPS was diminished if NSCLC patients received adjuvant chemotherapy, suggesting that HR suppression and associated sensitivity to platinum-based drugs counteracts the adverse prognosis associated with low RPS. Therefore, RPS may predict which therapies will be effective for individual patients, thereby enabling more personalized oncology care. PMID:24670686

  8. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease. PMID:3587892

  9. Chemotherapy for Stage II Colon Cancer.

    PubMed

    Varghese, Anna

    2015-12-01

    The adjuvant treatment of patients with stage II colon cancer is an area of controversy in medical oncology. Adjuvant chemotherapy aims to eradicate micrometastatic disease present at the time of surgery, preventing the development of distant metastatic disease and thereby curing those patients of their cancer. National and international guidelines for the adjuvant treatment of stage II colon cancer recommend a range of treatment options from observation to chemotherapy with single-agent or combination regimens, depending on the presence or absence of high-risk features (poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, report of < 12 lymph nodes, bowel obstruction, localized perforation, or positive margins). In the one prospective study designed to address the role of adjuvant chemotherapy in stage II colon cancer, a small but statistically significant benefit in overall survival was seen for those patients who received adjuvant chemotherapy; however, multiple meta-analyses and retrospective subgroup analyses have called these findings into question. Though there may be a role for adjuvant chemotherapy in the treatment of patients with stage II colon cancer, its incremental benefit is small, at best, and comes with the risks of real and rarely fatal complications of chemotherapy. PMID:26648796

  10. Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

    PubMed Central

    Shepherd, Frances A.; Domerg, Caroline; Hainaut, Pierre; Jänne, Pasi A.; Pignon, Jean-Pierre; Graziano, Stephen; Douillard, Jean-Yves; Brambilla, Elizabeth; Le Chevalier, Thierry; Seymour, Lesley; Bourredjem, Abderrahmane; Teuff, Gwénaël Le; Pirker, Robert; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Bandarchi, Bizhan; Ma, Xiaoli; Capelletti, Marzia; Soria, Jean-Charles; Tsao, Ming-Sound

    2013-01-01

    Purpose We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non–small-cell lung cancer (NSCLC). Methods KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Results Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). Conclusion KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT. PMID:23630215

  11. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial

    PubMed Central

    2014-01-01

    Background Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet. Methods From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation. Results At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020). Conclusions No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2

  12. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  13. Customizable radiotherapy enhancement (CuRE) for prostate cancer using platinum based nanoparticles

    NASA Astrophysics Data System (ADS)

    Cifter, Gizem

    New approach to prostate cancer (PCa) therapy titled "Customizable Radiotherapy Enhancement (CuRE)" employs cisplatin (C), carboplatin (Ca) and oxaliplatin (O) nanoparticles (CNPs, CaNPs and ONPs) as adjuvants to brachytherapy and external beam radiation therapy (EBRT), with the CNPs/CaNPs/ONPs released in situ from either brachytherapy spacers or fudicials loaded with the nanoparticles. The chemotherapy dose from the nanoparticles released in situ from within the prostate capsule, is enhanced by the physical dose due to photon interactions with the nanoparticles. The physical dose enhancement is due to low energy photons from the brachytherapy and EBRT sources interacting with the high-Z platinum component of the nanoparticles, causing emission of short-range photoelectrons to boost dose to the tumor. By varying the nanoparticle parameters, such as size, initial concentration, functionalization, location of spacer or fiducial, and intra-tumor biodistribution, the dose enhancement can be customized to maximize dose to tumor cells while minimizing toxicity to healthy cells. The hypothesis is that the CuRE approach will be a more efficacious method for concomitant cisplatin/carboplatin/oxaliplatin and radiotherapy treatment of localized prostate cancer due to significant dose boost to the PCa cells with minimal toxicity to healthy tissue. To investigate this hypothesis, microdosimetry calculations employing the energy loss formula of Cole were used to calculate the dose enhancement to the PCa cells from the CNPs/CaNPs/OPNs. The dose enhancement ratio (DEF) representing the ratio of the overall dose in the presence of CNPs/CaNPs/ONPs to the dose without CNPs/CaNPs/ONPs was determined for a range of CNP/CaNP/OPN concentrations up to their FDA approved limits. The dose enhancement to endothelial cells with (EDEF) with single concentration of cisplatin (42.8 mg/g) was found 2.6 with Pd-103. When EBRT source was used with single concentration of cisplatin, with 10cm x 10

  14. Current adjuvant treatment modalities for gastric cancer: From history to the future.

    PubMed

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-05-15

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  15. Current adjuvant treatment modalities for gastric cancer: From history to the future

    PubMed Central

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  16. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    SciTech Connect

    Bhatia, Sumita; Miller, Robert C. . E-mail: miller.robert@mayo.edu; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-10-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

  17. Influence of catalyst pretreatments on the catalytic oxidation of toluene over nanostructured platinum based spent catalyst.

    PubMed

    Shim, Wang-Geun; Lee, Jae-Wook; Kim, Sang-Chai

    2007-11-01

    In this study, we regenerated a nano-structured platinum based spent catalyst by applying thermal gas and acid pretreatment and examined the influence of treatment on the catalytic oxidation of toluene. The spent catalysts were pretreated with air, hydrogen and six different acid aqueous solutions (HCl, H2SO4, HNO3, H3PO4, CH3COOH and C2H2O4). The physicochemical properties of the parent and its modified catalysts were characterized by XRD, BET, TEM, and ICP. The results of light-off curves showed that air and hydrogen treated catalysts were more active than the parent catalyst. In addition, the catalytic activities of toluene oxidation for acid aqueous treated samples were identical with the order of Pt/Al ratio. PMID:18047055

  18. Can the response to a platinum-based therapy be predicted by the DNA repair status in non-small cell lung cancer?

    PubMed

    Macerelli, Marianna; Ganzinelli, Monica; Gouedard, Cedric; Broggini, Massimo; Garassino, Marina Chiara; Linardou, Helena; Damia, Giovanna; Wiesmüller, Lisa

    2016-07-01

    Preclinical evidence has been accumulating on the impact of the DNA repair status on the sensitivity/resistance to anticancer agents in different tumor types, including lung cancer. The possibility to predict the response to therapy, and specifically to platinum agents, based on tumor specific DNA repair functionality would enable to tailor its use only in those patients with maximum chances to respond, avoiding the burden of toxicity in those ones with lesser chances. We here reviewed the clinical evidence on the prognostic role of DNA repair markers and/or functional assays in predicting the response to a platinum-based chemotherapy in lung cancer patients. Consequently, we focused on those proteins involved in pathways repairing platinum induced DNA inter-strand and intra-strand crosslinks. Most promising clinical trials targeting the nucleotide repair protein ERCC1 in non-small cell lung cancer later on suffered from serious drawbacks. Nevertheless, these results spurred a variety of preclinical studies on a multitude of alternative DNA repair markers. However so far, no one of the analyzed DNA repair markers can be considered a reliable and mature biomarker for selecting patients. We discuss the reasons for such failure which discloses novel strategies for the future. PMID:27262017

  19. Urinary excretion of platinum, arsenic and selenium of cancer patients from the Antofagasta region in Chile treated with platinum-based drugs

    PubMed Central

    2012-01-01

    Background Arsenic exposure increases the risk of non-cancerous and cancerous diseases. In the Antofagasta region in Chile, an established relationship exists between arsenic exposure and the risk of cancer of the bladder, lung and skin. Platinum-based drugs are first-line treatments, and many works recognise selenium as a cancer-fighting nutrient. We characterised the short-term urinary excretion amounts of arsenic, selenium and platinum in 24-h urine samples from patients with lung cancer and those with cancer other than lung treated with cisplatin or/and carboplatin. As - Se - Pt inter-element relationships were also investigated. Results The amounts of platinum excreted in urine were not significantly different between patients with lung cancer and those with other cancers treated with cisplatin, despite the significant variation in platinum amounts supplied from platinum-based drugs. In general, the analytical amounts of excreted selenium were greater than those for arsenic, which could imply that platinum favours the excretion of selenium. For other types of cancers treated with drugs without platinum, excretion of selenium was also greater than that of arsenic, suggesting an antagonist selenium-anti-cancer drug relationship. Conclusions Regards the baseline status of patients, the analytical amounts of excreted Se is greater than those for As, particularly, for cisplatin chemotherapy. This finding could imply that for over the As displacement Pt favours the excretion of Se. The analytical amounts of excreted Se were greater than those for As, either with and without Pt-containing drugs, suggesting an antagonist Se-anti-cancer drug relationship. However, it seemed that differences existed between As - Se - Pt inter-element associations in patients treated for lung cancer in comparison with those treated for cancer other than lung. Therefore, knowledge obtained in this work, can contribute to understanding the arsenic cancer mechanism and the As - Se - Pt

  20. Adjuvant therapy for gastric cancer: Current and future directions

    PubMed Central

    Foo, Marcus; Leong, Trevor

    2014-01-01

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies. PMID:25320509

  1. Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

    PubMed

    Pagani, Olivia; Gelber, Shari; Simoncini, Edda; Castiglione-Gertsch, Monica; Price, Karen N; Gelber, Richard D; Holmberg, Stig B; Crivellari, Diana; Collins, John; Lindtner, Jurij; Thürlimann, Beat; Fey, Martin F; Murray, Elizabeth; Forbes, John F; Coates, Alan S; Goldhirsch, Aron

    2009-08-01

    To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high. PMID:18953651

  2. Adjuvant and neoadjuvant treatment in pancreatic cancer

    PubMed Central

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes “standard” adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients. PMID:22529684

  3. Cancer Chemotherapy

    MedlinePlus

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  4. Cancer Chemotherapy

    MedlinePlus

    ... cells grow and die in a controlled way. Cancer cells keep forming without control. Chemotherapy is drug ... Your course of therapy will depend on the cancer type, the chemotherapy drugs used, the treatment goal ...

  5. Role of transporters in the distribution of platinum-based drugs

    PubMed Central

    Harrach, Saliha; Ciarimboli, Giuliano

    2015-01-01

    Platinum derivatives used as chemotherapeutic drugs such as cisplatin and oxaliplatin have a potent antitumor activity. However, severe side effects such as nephro-, oto-, and neurotoxicity are associated with their use. Effects and side effects of platinum-based drugs are in part caused by their transporter-mediated uptake in target and non target cells. In this mini review, the transport systems involved in cellular handling of platinum derivatives are illustrated, focusing on transporters for cisplatin. The copper transporter 1 seems to be of particular importance for cisplatin uptake in tumor cells, while the organic cation transporter (OCT) 2, due to its specific organ distribution, may play a major role in the development of undesired cisplatin side effects. In polarized cells, e.g., in renal proximal tubule cells, apically expressed transporters, such as multidrug and toxin extrusion protein 1, mediate secretion of cisplatin and in this way contribute to the control of its toxic effects. Specific inhibition of cisplatin uptake transporters such as the OCTs may be an attractive therapeutic option to reduce its toxicity, without impairing its antitumor efficacy. PMID:25964760

  6. Salvage chemotherapy with amrubicin and platinum for relapsed thymic carcinoma: experience in six cases.

    PubMed

    Koizumi, Tomonobu; Agatsuma, Toshihiko; Ichiyama, Takashi; Yokoyama, Toshiki; Ushiki, Atsuhito; Komatsu, Yoshimichi; Tanabe, Tsuyoshi; Kobayashi, Takashi; Yoshikawa, Sumiko; Yasuo, Masanori; Yamamoto, Hiroshi; Kubo, Keishi; Hachiya, Tsutomu

    2010-06-01

    It has been reported that cisplatin-based chemotherapy shows beneficial effects in certain patients with advanced thymic carcinoma. However, the usefulness of salvage therapy has not been reported. We focused on a new anthracycline agent, amrubicin, combined with platinum compounds as salvage chemotherapy in patients with thymic carcinoma. Six cases of unresectable and locally advanced thymic carcinoma relapsed from prior cisplatin-containing chemotherapy were treated with amrubicin (30-40 mg/m(2) day 1-3) plus platinum compounds (cisplatin 60 mg/m(2) day 1 or nedaplatin 70 mg/m(2) day 1) chemotherapy as salvage chemotherapy. Two patients showed a partial response. However, Grade 3/4 neutropenia and thrombocytopenia occurred in all and two of the patients, respectively. We conclude that thymic carcinoma is sensitive to platinum-based chemotherapy and that amrubicin appears to have significant activity against thymic carcinoma. The major toxicity is hematological toxicities. PMID:19415537

  7. Systemic adjuvant therapies in renal cell carcinoma.

    PubMed

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  8. Neo-adjuvant capecitabine chemotherapy in women with newly diagnosed locally advanced breast cancer in a resource-poor setting (Nigeria): efficacy and safety in a phase II feasibility study.

    PubMed

    Arowolo, Olukayode A; Njiaju, Uchenna O; Ogundiran, Temidayo O; Abidoye, Oyewale; Lawal, Olukayode O; Obajimi, Millicent; Adetiloye, Adebayo V; Im, Hae K; Akinkuolie, Akinbolaji A; Oluwasola, Abideen; Adelusola, Kayode; Kayode, Adesunkanmi A; Agbakwuru, Augustine E; Oduntan, Helen; Babalola, Chinedum P; Fleming, Gini; Olopade, Olusola C; Falusi, Adeyinka Gladys; Durosinmi, Muheez A; Olopade, Olufunmilayo I

    2013-01-01

    The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m(2) twice daily (2,000 mg/m(2) total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11-59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20-70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand-foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo-adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted. PMID:23865786

  9. Neo-adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource-poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

    PubMed Central

    Arowolo, Olukayode A; Njiaju, Uchenna O; Ogundiran, Temidayo O; Abidoye, Oyewale; Lawal, Olukayode O; Obajimi, Millicent; Adetiloye, Adebayo V; Im, Hae K; Akinkuolie, Akinbolaji A; Oluwasola, Abideen; Adelusola, Kayode; Kayode, Adesunkanmi A; Agbakwuru, Augustine E; Oduntan, Helen; Babalola, Chinedum P; Fleming, Gini; Olopade, Olusola C; Falusi, Adeyinka Gladys; Durosinmi, Muheez A; Olopade, Olufunmilayo I

    2013-01-01

    The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m2 twice daily (2,000 mg/m2 total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo-adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted. PMID:23865786

  10. [Prostate cancer and chemotherapy].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Bladou, Franck; Viens, Patrice

    2007-07-01

    Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID:17845990

  11. Platinum Based Chemotherapy or Observation in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

    ClinicalTrials.gov

    2015-05-14

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  12. Role of ERCC1 variants in response to chemotherapy and clinical outcome of advanced non-small cell lung cancer.

    PubMed

    Huang, Shao-jun; Wang, Yu-fei; Jin, Zhi-yong; Sun, Jia-yang; Guo, Zhan-lin

    2014-05-01

    Excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum-F (XPF) in the nucleotide excision repair pathway have been effectively repairing DNA damage induced by chemotherapeutic agents. We conducted a cohort study to assess the associations of ERCC1 and XPF polymorphisms with response to platinum-based chemotherapy and clinical outcome of non-small-cell lung cancer (NSCLC). One hundred eighty-seven NSCLC cases treated with platinum-based chemotherapy were prospectively analyzed. The predictive value of four SNPs in ERCC1 and two SNPs in XPF in patient's response and survival related to platinum-based chemotherapy were analyzed using χ(2) tests, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The overall chemotherapy response rate for treatment was 51.18%. One hundred eighty-seven patients were followed up, and the median survival time is 17.6 months (ranged from 1 to 50 months). A total of 106 patients (56.68%) died from NSCLC during the follow-up period. Carriers of the rs3212986 AA and A allele had a borderline significantly lower response rate to the chemotherapy. In the Cox proportional hazards model, patients carrying the ERCC1 rs3212986 AA genotype were significantly associated with increased risk of death from NSCLC when compared with those with CC genotype as a reference variable. This study reported that variants in ERCC1 can be used as a prognostic maker to platinum-based chemotherapy in NSCLC patients. PMID:24370899

  13. Pathological complete response after neoadjuvant therapy for rectal cancer and the role of adjuvant therapy.

    PubMed

    Nelson, Valerie M; Benson, Al B

    2013-04-01

    Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy. PMID:23381584

  14. Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.

    PubMed

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  15. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    PubMed Central

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  16. Nano-structured Platinum-based Catalysts for the Complete Oxidation of Ethylene Glycol and Glycerol

    NASA Astrophysics Data System (ADS)

    Falase, Akinbayowa

    Direct alcohol fuel cells are a viable alternative to the traditional hydrogen PEM fuel cell. Fuel versatility, integration with existing distribution networks, and increased safety when handling these fuels increases their appeal for portable power applications. In order to maximize their utility, the liquid fuel must be fully oxidized to CO2 so as to harvest the full amount of energy. Methanol and ethanol are widely researched as potential fuels to power these devices, but methanol is a toxic substance, and ethanol has a much lower energy density than other liquids such as gasoline or glucose. Oxidation of complex fuels is difficult to realize, due to difficulty in breaking carbon-carbon bonding and poisoning of the catalysts by oxidative byproducts. In order to achieve the highest efficiency, an anode needs to be engineered in such a way as to maximize activity while minimizing poisoning effects of reaction byproducts. We have engineered an anode that uses platinum-based catalysts that is capable of completely oxidizing ethylene glycol and glycerol in neutral and alkaline media with little evidence of CO poisoning. We have constructed a hybrid anode consisting of a nano-structured PtRu electrocatayst with an NAD-dependent alcohol dehydrogenase for improved oxidation of complex molecules. A nano-structured PtRu catalyst was used to oxidize ethylene glycol and glycerol in neutral media. In situ infrared spectroscopy was used to verify complete oxidation via CO2 generation. There was no evidence of poisoning by CO species. A pH study was performed to determine the effect of pH on oxidative current. The peak currents did not trend at 60 mV/pH unit as would be expected from the Nernst equation, suggesting that adsorption of fuel to the surface of the electrode is not an electron-transfer step. We synthesized nano-structured PtRu, PtSn, and PtRuSn catalysts for oxidation of ethylene glycol and glycerol in alkaline media. The PtRu electrocatalyst the highest oxidative

  17. Assessment of microtubule-associated protein (MAP)-Tau expression as a predictive and prognostic marker in TACT; a trial assessing substitution of sequential docetaxel for FEC as adjuvant chemotherapy for early breast cancer.

    PubMed

    Irshad, S; Gillett, C; Pinder, S E; A'hern, R P; Dowsett, M; Ellis, I O; Bartlett, J M S; Bliss, J M; Hanby, A; Johnston, S; Barrett-Lee, P; Ellis, P; Tutt, A

    2014-04-01

    The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients. ER, PR, HER2 from the TACT trial and Tau protein expression was determined by immunohistochemistry on duplicate TMAs. Two parallel scoring systems were generated for Tau expression ('dichotomised' vs. 'combined' score). The positivity rate of Tau expression was 50 % in the trial population (n = 2,483). Tau expression correlated positively with ER (p < 0.001) and PR status (p < 0.001); but negatively with histological grade (p < 0.001) and HER2 status (p < 0.001). Analyses with either scoring systems for Tau expression demonstrated no significant interaction between Tau expression and efficacy of docetaxel. Contrary to the hypothesis that taxane benefit would be enriched in Tau negative/low patients, the only groups with a suggestion of a reduced event rate in the taxane group were the HER2-positive, Tau positive subgroups. Tau expression was seen to be a prognostic factor on univariate analysis associated with an improved DFS, independent of the treatment group (p < 0.001). It had no prognostic value in ER-negative tumours and the weak prognostic effect of Tau in ER-positive tumours (p = 0.02) diminished, when considering ER as an ordinal variable. On multivariable analyses, Tau had no prognostic value in either group. In addition, no significant interaction between Tau expression and benefit from docetaxel in patients within the PR-positive and negative subsets was seen. This is now the second large adjuvant study, and the first with quantitative analysis of ER and Tau expression, failing to show an association between Tau and taxane benefit with limited utility as a prognostic marker for Tau in ER-positive early breast cancer patients. PMID:24519386

  18. Trends in vaccine adjuvants.

    PubMed

    Schijns, Virgil E J C; Lavelle, Ed C

    2011-04-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a century and have been particularly effective at promoting protective humoral immunity. However, alum is not optimally effective for diseases where cell-mediated immunity is required for protection. Furthermore, adjuvants including oil-in-water emulsions have shown improved efficacy for avian influenza protection suggesting that even for diseases where humoral immunity can confer protection, there is scope for developing improved adjuvants. There have been major developments in antigen discovery over the past decade, which has accelerated the vaccine development process for new indications and this demands a new generation of adjuvants that can drive and specifically direct the desired immune responses. A number of systems are under investigation that combine different types of adjuvants into specific formulations with greater activity. Additionally, targeting of vaccines to specific immune cells shows great promise. In the case of cancer and chronic infectious diseases, it may be difficult to develop effective vaccines without blocking immune regulatory pathways, which impede cell-mediated responses. However, increased understanding of immunology and particularly the innate immune system is informing vaccine adjuvant research and consequently driving the development of novel and specifically directed vaccine adjuvant strategies. In this article we address the importance of adjuvants in vaccine development, the known mode of action of specific adjuvants and recent developments in this important field. PMID:21506650

  19. Single nucleotide polymorphisms in glutathione S-transferase P1 and M1 genes and overall survival of patients with ovarian serous cystadenocarcinoma treated with chemotherapy

    PubMed Central

    CONG, LAN-XIANG; ZHAI, XIANG-HONG; WU, FENG-XIA; ZHU, DONG-YI; WANG, AN-CONG

    2016-01-01

    The effects of platinum-based drugs are controlled by genes that are involved in DNA detoxification, including glutathione S-transferase (GST)P1 and GSTM1, which have been associated with increased benefits in the chemotherapeutic treatment of patients with ovarian cancer. The present study assessed the effect of single nucleotide polymorphisms in GST genes on the overall survival (OS) of patients with ovarian serous cystadenocarcinoma that were treated with chemotherapy. A total of 95 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms in the patients were genotyped using the following methods: Pyrosequencing, to identify GSTP1 Ile105Val; a relative quantification method, to identify the copy number variation in GSTM1; and polymerase chain reaction followed by gel electrophoresis, to identify the null vs. non-null genotypes of GSTM1. The association between genotypes and OS of patients was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The OS of patients treated with paclitaxel + carboplatin-based chemotherapy was significantly increased, compared with patients treated with alternative forms of chemotherapy (P=0.035). The OS of patients did not differ significantly between different GSTP1 genotypes (log-rank test, P=0.17). Cox proportional hazards regression analysis revealed that, since the start of the treatment, there was not a significant association between the GSTP1 isoleucine allele and the OS for heterozygous carriers of the isoleucine allele [hazards ratio (HR), 1.78; 95% confidence interval (CI), 0.77–4.12; P=0.18] and no homozygous carriers of the valine allele had been detected (HR, 0.00). There was no significant difference between GSTM1 genotypes, according to Kaplan-Meier survival analysis (log-rank test, P=0.83). Patients that possessed ≤1 copy of GSTM1 exhibited no decrease in OS (HR, 0.96; 95% CI, 0.37–2.51; P=0.94), compared with patients that

  20. Phase III Multi-Institutional Trial of Adjuvant Chemotherapy With Paclitaxel, Estramustine, and Oral Etoposide Combined With Long-Term Androgen Suppression Therapy and Radiotherapy Versus Long-Term Androgen Suppression Plus Radiotherapy Alone for High-Risk Prostate Cancer: Preliminary Toxicity Analysis of RTOG 99-02

    SciTech Connect

    Rosenthal, Seth A. Bae, Kyoungwha; Pienta, Kenneth J.; Sobczak, Mark L.; Asbell, Sucha O.; Rajan, Raghu; Kerlin, Kevin J.; Michalski, Jeff M.; Sandler, Howard M.

    2009-03-01

    Purpose: Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity. Methods and Materials: High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score {>=}7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began. Results: The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. Conclusion: TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.

  1. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

    SciTech Connect

    Rosenthal, Seth A.; Hunt, Daniel; Sartor, A. Oliver; Pienta, Kenneth J.; Gomella, Leonard; Grignon, David; Rajan, Raghu; Kerlin, Kevin J.; Jones, Christopher U.; Dobelbower, Michael; Shipley, William U.; Zeitzer, Kenneth; Hamstra, Daniel A.; Donavanik, Viroon; Rotman, Marvin; Hartford, Alan C.; Michalski, Jeffrey; Seider, Michael; Kim, Harold; and others

    2015-10-01

    Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for

  2. P11: 18FDG-PET/CT for early prediction of response to first line platinum chemotherapy in advanced thymic epithelial tumors

    PubMed Central

    Palmieri, Giovannella; Ottaviano, Margaret; Del Vecchio, Silvana; Segreto, Sabrina; Tucci, Irene; Damiano, Vincenzo

    2015-01-01

    Background To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiological markers, to predict the response disease to first line platinum based chemotherapy in advanced thymic epithelial tumors (TETs). Methods Twenty patients with diagnosis of TET and stage of disease III and IV sec, Masaoka-Koga, were retrospectively included in this monocentric study. Different pre-treatment clinical, biological and pathological parameters, including histotype sec, WHO 2004 and stage of disease sec, Masaoka-Koga were assessed. Tumor glucose metabolism at baseline and its change after the first line platinum based chemotherapy (from 4 to 6 cycles) were assessed using FDG-PET, moreover the response disease was assessed using total body CT scan for the evaluation of RECIST criteria 1.1. Results Twelve patients had an objective response to the first line platinum based chemotherapy according RECIST criteria 1.1 and all of them started with a SUVmax at baseline major than 5, indeed the other eight patients, non-responders to chemotherapy, had a SUVmax at baseline minor than 5. Conclusions It is important to define the chemosensitivity of advanced TETs early. Combining bio-pathological parameters with the metabolism at baseline assessed with FDG-PET can help the physician to early predict the probability of obtaining a disease response to first line platinum based chemotherapy. The SUVmax cut off of 5 at 18FDG-PET/CT performed at baseline treatment might be a new parameter for choosing the most powerful first line of chemotherapy. Given these results, further prospective studies are needed to establish a new first line therapy in advanced TETs with a low SUVmax at baseline, non-responders to conventional chemotherapy.

  3. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  4. Postoperative adjuvant radiotherapy for patients with gastric adenocarcinoma.

    PubMed

    Lim, Do Hoon

    2012-12-01

    In gastric adenocarcinoma, high rates of loco-regional recurrences have been reported even after complete resection, and various studies have been tried to find the role of postoperative adjuvant therapy. Among them, Intergroup 0116 trial was a landmark trial, and demonstrated the definite survival benefit in adjuvant chemoradiotherapy, compared with surgery alone. However, the INT 0116 trial had major limitation for global acceptance of the INT 0116 regimen as an adjuvant treatment modality because of the limited lymph node dissection. Lately, several randomized studies that were performed to patients with D2-dissected gastric cancer were published. This review summarizes the data about patterns of failure after surgical resection and the earlier prospective studies, including INT 0116 study. Author will introduce the latest studies, including ARTIST trial and discuss whether external beam radiotherapy should be applied to patients receiving extended lymph node dissection and adjuvant chemotherapy. PMID:23346491

  5. Improving Systemic Chemotherapy for Bladder Cancer.

    PubMed

    Rose, Tracy L; Milowsky, Matthew I

    2016-05-01

    Systemic chemotherapy is integral to the management of muscle-invasive and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy has been increasingly utilized for muscle-invasive BCa over the past several years, and several options for cisplatin-based regimens have emerged. Adjuvant chemotherapy may be considered for select patients who did not receive neoadjuvant therapy. Systemic chemotherapy added to radiotherapy is a critical component of a bladder-preserving approach and superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa for more than three decades. Novel targeted agents are in development fueled by the recent molecular characterization of BCa. Recent trials of immunotherapy have demonstrated the possibility of a less toxic and potentially more effective treatment for metastatic disease. It is an extremely exciting time for BCa research, and much needed improvements in systemic treatment are most certainly on the horizon. PMID:26984414

  6. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  7. Chemotherapy and Your Mouth

    MedlinePlus

    ... Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being Treated With Chemotherapy ... Back to Top How Does Chemotherapy Affect the Mouth? Chemotherapy is the use of drugs to treat ...

  8. [Adjuvant drug therapies for breast cancer].

    PubMed

    Huovinen, Riikka; Auvinen, Päivi; Mattson, Johanna; Joensuu, Heikki

    2015-01-01

    Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. PMID:26245052

  9. Chemotherapy in elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth; Westeel, Virginie; Zalcman, Gérard; Milleron, Bernard

    2011-12-01

    Because of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated. PMID:21893363

  10. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice

    PubMed Central

    Lesterhuis, W. Joost; Punt, Cornelis J.A.; Hato, Stanleyson V.; Eleveld-Trancikova, Dagmar; Jansen, Bastiaan J.H.; Nierkens, Stefan; Schreibelt, Gerty; de Boer, Annemiek; Van Herpen, Carla M.L.; Kaanders, Johannes H.; van Krieken, Johan H.J.M.; Adema, Gosse J.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2011-01-01

    Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor immune responses. Therapeutic interventions aimed at disrupting these inhibitory mechanisms have been shown to enhance antitumor immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cytotoxic cancer chemotherapeutics on immune inhibitory pathways. We observed that exposure to platinum-based chemotherapeutics markedly reduced expression of the T cell inhibitory molecule programmed death receptor-ligand 2 (PD-L2) on both human DCs and human tumor cells. Downregulation of PD-L2 resulted in enhanced antigen-specific proliferation and Th1 cytokine secretion as well as enhanced recognition of tumor cells by T cells. Further analysis revealed that STAT6 controlled downregulation of PD-L2. Consistent with these data, patients with STAT6-expressing head and neck cancer displayed enhanced recurrence-free survival upon treatment with cisplatin-based chemoradiation compared with patients with STAT6-negative tumors, demonstrating the clinical relevance of platinum-induced STAT6 modulation. We therefore conclude that platinum-based anticancer drugs can enhance the immunostimulatory potential of DCs and decrease the immunosuppressive capability of tumor cells. This dual action of platinum compounds may extend their therapeutic application in cancer patients and provides a rationale for their use in combination with immunostimulatory compounds. PMID:21765211

  11. Update in Cancer Chemotherapy: Gastrointestinal Cancer—Colorectal Cancer, Part 2

    PubMed Central

    Wright, Jane C.

    1986-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy. In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data. PMID:3519988

  12. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    SciTech Connect

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  13. Cytotoxic Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer in Taiwan: Daily Practice

    PubMed Central

    Liang, Yi-Hsin; Shao, Yu-Yun; Liao, Bin-Chi; Lee, Ho-Sheng; Yang, James Chih-Hsin; Chen, Ho-Min; Chiang, Chun-Ju; Cheng, Ann-Lii; Lai, Mei-Shu

    2016-01-01

    Aim: Cytotoxic chemotherapy is the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without specific gene alterations. This study examined the prescription pattern and the survival outcome of cytotoxic chemotherapy regimens in daily practice in Taiwan. Methods:We established a population-based cohort of patients diagnosed with advanced NSCLC between 2005 and 2009 using the databases of Taiwan Cancer Registry and National Health Insurance in Taiwan. We then analyzed chemotherapy prescriptions and the survival outcomes of patients. Results:A total of 25,008 patients with advanced NSCLC were identified, 17,443 (70.0%) of which received first-line chemotherapy and were therefore included in this study. Among them, 11,551 (66.2%) patients had adenocarcinoma and 3,292 (18.9%) patients had squamous cell carcinoma (SCC). Approximately 70% of the patients were diagnosed with NSCLC in medical centers. Platinum-based doublet chemotherapy was administered to 66.9% of the patients. Among all chemotherapy regimens, platinum with gemcitabine (33.8%) was the most common, irrespective of geographic region. The second and third most common regimens were vinorelbine alone (13.0%) and platinum with docetaxel (11.6%). The prevalence of platinum-based doublet chemotherapy regimens decreased from 71.4% in 2005 to 64.1% in 2009. Among patients with adenocarcinoma histology, those who received platinum with pemetrexed had longer OS than did patients who received other platinum-based regimens (p < 0.001). Conclusion: Our findings reaffirm that in real-world practice, treatment plans of advanced NSCLC should be drawn up according to histology type. PMID:27471567

  14. 26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines

    PubMed Central

    Seoane, Samuel; Bermudez, Maria A.; Sendon-Lago, Juan; Martinez-Ordoñez, Anxo; Abdul-Hadi, Soraya; Maestro, Miguel; Mouriño, Antonio; Perez-Fernandez, Roman

    2013-01-01

    It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25D) and some of its analogues have antitumor activity. 1,25D labeled with deuterium (26,26,26,27,27,27-hexadeuterated 1α,25-dihydroxyvitamin D3, or 1,25D-d6) is commonly used as internal standard for 1,25D liquid chromatography-mass spectrometry (LC-MS) quantification. In the present study using human breast cancer cell lines, the biological activity of 1,25D-d6 administered alone and in combination with two commonly used antineoplastic agents, 5-fluorouracil and etoposide, was evaluated. Using an MTT assay, flow cytometry, and western blots, our data demonstrated that 1,25D-d6 has effects similar to the natural hormone on cell proliferation, cell cycle, and apoptosis. Furthermore, the combination of 1,25D-d6 and etoposide enhances the antitumoral effects of both compounds. Interestingly, the antitumoral effect is higher in the more aggressive MDA-MB-231 breast cancer cell line. Our data indicate that 1,25D-d6 administered alone or in combination with chemotherapy could be a good experimental method for accurately quantifying active 1,25D levels in cultures or in biological fluids, on both in vitro breast cancer cell lines and in vivo animal experimental models. PMID:24378752

  15. Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer.

    PubMed

    Lohmann, Ana Elisa; Chapman, Judy-Anne W; Burnell, Margot J; Levine, Mark Norman; Tsvetkova, Elena; Pritchard, Kathleen I; Gelmon, Karen A; O'Brien, Patti; Han, Lei; Rugo, Hope S; Albain, Kathy S; Perez, Edith A; Vandenberg, Theodore A; Chalchal, Haji I; Sawhney, Ravinder Pal Singh; Shepherd, Lois E; Goodwin, Pamela Jean

    2015-04-01

    Low vitamin D levels have been associated with poor breast cancer outcomes in observational studies. We examined the association of vitamin D blood levels with relapse-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the MA.21 randomized clinical trial. Fasting blood was collected pre-chemotherapy in 934/2104 (44.4 %) of subjects; 25 hydroxy vitamin D was measured (radioimmunoassay, Diasorin) in one batch. Vitamin D was assessed as a transformed continuous factor, and categorically (quartiles and clinical classifications). Univariate and multivariate prognostic analyses (adjusted for treatment, stratification factors, and baseline imbalances) were performed using Cox models. Most patients were young (median 47.8 years), white (91.6 %) and premenopausal (69.4 %) with grade III (52 %), HER2 negative or missing (89.5 %), ER positive (61.9 %), T1-2 (89.4 %), N + (72.7 %) breast cancer. Compared to the full population, those with vitamin D levels were more likely to be white, PS 1 or 2, to have undergone mastectomy, and to have an ER + tumor. Mean vitamin D was 69.7 nmol/L (27.9 ng/ml) and did not vary by tumor subtype. The majority (80.5 %) had levels >50 nmol/L (20 ng/ml), considered adequate by Institute of Medicine. Continuous vitamin D was not multivariately associated with RFS, BCSS, or OS (p = 0.36, 0.26, 0.33, respectively); categorical vitamin D was also not associated with outcome. Vitamin D associations with RFS did not differ within ER/HER2 subgroups. There was no evidence that vitamin D blood level was associated with RFS, BCSS, and OS in MA.21; the majority of subjects had adequate vitamin D levels at study entry. PMID:25833209

  16. [Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?].

    PubMed

    Piura, Benjamin

    2014-09-01

    The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma. PMID:25417488

  17. [Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?............... ].

    PubMed

    Piura, Benjamin

    2014-09-01

    The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma. PMID:25507216

  18. Mechanisms of Action of Adjuvants

    PubMed Central

    Awate, Sunita; Babiuk, Lorne A.; Mutwiri, George

    2013-01-01

    Adjuvants are used in many vaccines, but their mechanisms of action are not fully understood. Studies from the past decade on adjuvant mechanisms are slowly revealing the secrets of adjuvant activity. In this review, we have summarized the recent progress in our understanding of the mechanisms of action of adjuvants. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. It appears that adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses. Understanding the mechanisms of action of adjuvants will provide critical information on how innate immunity influences the development of adaptive immunity, help in rational design of vaccines against various diseases, and can inform on adjuvant safety. PMID:23720661

  19. Retinoblastoma: achieving new standards with methods of chemotherapy.

    PubMed

    Kaliki, Swathi; Shields, Carol L

    2015-02-01

    The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827539

  20. Adjuvant therapy for pancreas cancer in an era of value based cancer care

    PubMed Central

    Ahn, Daniel H.; Williams, Terence M.; Goldstein, Daniel A.; El-Rayes, Bassel; Bekaii-Saab, Tanios

    2016-01-01

    In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true “net health benefit” from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer. PMID:26620819

  1. Adjuvant therapy for pancreas cancer in an era of value based cancer care.

    PubMed

    Ahn, Daniel H; Williams, Terence M; Goldstein, Daniel A; El-Rayes, Bassel; Bekaii-Saab, Tanios

    2016-01-01

    In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true "net health benefit" from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer. PMID:26620819

  2. Utility of adjuvant systemic therapy in melanoma

    PubMed Central

    Eggermont, A. M. M.; Testori, A.; Marsden, J.; Hersey, P.; Quirt, I.; Petrella, T.; Gogas, H.; MacKie, R. M.; Hauschild, A.

    2009-01-01

    The lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in several clinical trials; however, without a clinically significant effect on overall survival (OS). A recently conducted meta-analysis demonstrated prolongation of disease-free survival (DFS) in 7% and OS benefit in 3% of IFN-treated patients when compared with observation-only patients. There were no clear differences for the dose and duration of treatment observed. Observation is still an appropriate control arm in adjuvant clinical trials. Regional differences exist in Europe in the adjuvant use of IFN. In Northwest Europe, IFN is infrequently prescribed. In Central and Mediterranean Europe, dermatologists commonly prescribe low-dose IFN therapy for AJCC stage II and III disease. High-dose IFN regimens are not commonly used. The population of patients that may benefit from IFN needs to be further characterised, potentially by finding biomarkers that can predict response. Such studies are ongoing. PMID:19617295

  3. Sustainable complete remission in recurrence yolk sac tumor patient treated with tandem high-dose chemotherapy and autologous stem cell.

    PubMed

    Abdullah, N A; Wang, P N; Huang, K G; Adlan, A S; Casanova, J

    2013-01-01

    A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy. PMID:23781595

  4. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    NASA Astrophysics Data System (ADS)

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-05-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  5. A first principles study of pristine and Al-doped boron nitride nanotubes interacting with platinum-based anticancer drugs

    NASA Astrophysics Data System (ADS)

    Shakerzadeh, Ehsan; Noorizadeh, Siamak

    2014-03-01

    Interaction of cis-platin and neda-platin, two conventional platinum-based anticancer drugs, with pristine [8,8] and Al-doped [8,0] boron nitride nanotubes (BNNTs) are investigated using the density functional theory (DFT) method. The obtained results indicate that cis-platin and neda-platin weakly interact with pristine zig zag or armchair BNNTs with a little dependency on the adsorbing positions; while both cis-platin and neda-platin are preferentially adsorbed onto the Al atom of the Al-doped BNNT with considerable adsorption energies. Therefore the Al-doped-BNNT might be an efficient carrier for delivery of these drugs in nanomedicine domain. The electronic structures of the stable configurations are also investigated through both DOS and PDOS spectra. The obtained results introduce the Al-doped-BNNT as an efficient carrier for delivery of cis-platin and neda-platin in nanomedicine domain.

  6. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    PubMed Central

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-01-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted. PMID:27150583

  7. Prognostic significance of X-ray cross-complementing gene 1 expression in gastric cancer

    PubMed Central

    Wang, Jian; Wang, Tongshan; Xu, Jun; Chen, WenJiao; Shi, Wei; Cheng, Jianfeng

    2016-01-01

    Objective The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. Conclusions XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.

  8. Novel adjuvant systems.

    PubMed

    McCluskie, M J; Weeratna, R D

    2001-11-01

    Vaccination remains the single most valuable tool in the prevention of infectious disease. Nevertheless, there exists a need to improve the performance of existing vaccines such that fewer boosts are needed or to develop novel vaccines. For the development of effective vaccines for humans, a great need exists for safe and effective adjuvants. A number of novel adjuvants have been reported in recent years including: i) bacterial toxins such as cholera toxin, CT, and the Escherichia coli heat-labile enterotoxin, LT; ii) less toxic derivatives of CT and LT; iii) endogenous human immunomodulators, such as IL-2, IL-12, GM-CSF; iv) hormones; v) lipopeptides; vi) saponins, such as QS-21; vii) synthetic oligonucleotides containing CpG motifs (CpG ODN); viii) lipid 'A derivatives, such as monophosphoryl lipid A, MPL, and ix) muramyl dipeptide (MDP) derivatives. Herein, we will review recent findings using these novel adjuvant systems. PMID:12455400

  9. Glutathione modified CdTe quantum dots as a label for studying DNA interactions with platinum based cytostatics.

    PubMed

    Ryvolova, Marketa; Smerkova, Kristyna; Chomoucka, Jana; Hubalek, Jaromir; Adam, Vojtech; Kizek, Rene

    2013-03-01

    Cisplatin, carboplatin, and oxaliplatin represent three generations of platinum based drugs applied successfully for cancer treatment. As a consequence of the employment of platinum based cytostatics in the cancer treatment, it became necessary to study the mechanism of their action. Current accepted opinion is the formation of Pt-DNA adducts, but the mechanism of their formation is still unclear. Nanomaterials, as a progressively developing branch, can offer a tool for studying the interactions of these drugs with DNA. In this study, fluorescent CdTe quantum dots (QDs, λem = 525 nm) were employed to investigate the interactions of platinum cytostatics (cisplatin, carboplatin, and oxaliplatin) with DNA fragment (500 bp, c = 25 μg/mL). Primarily, the fluorescent behavior of QDs in the presence of platinum cytostatics was monitored and major differences in the interaction of QDs with tested drugs were observed. It was found that the presence of carboplatin (c = 0.25 mg/mL) had no significant influence on QDs fluorescence; however cisplatin and oxaliplatin quenched the fluorescence significantly (average decrease of 20%) at the same concentration. Subsequently, the amount of platinum incorporated in DNA was determined by QDs fluorescence quenching. Best results were reached using oxaliplatin (9.4% quenching). Linear trend (R(2) = 0.9811) was observed for DNA platinated by three different concentrations of oxaliplatin (0.250, 0.125, and 0.063 mg/mL). Correlation with differential pulse voltammetric measurements provided linear trend (R(2) = 0.9511). As a conclusion, especially in the case of oxaliplatin-DNA adducts, the quenching was the most significant compared to cisplatin and nonquenching carboplatin. PMID:23400813

  10. [Induction chemotherapy for locally advanced cervical cancer].

    PubMed

    Morkhov, K Yu; Nechushkina, V M; Kuznetsov, V V

    2015-01-01

    The main methods of treatment for cervical cancer are surgery, radiotherapy or their combination. During past two decades chemotherapy are increasingly being used not only in patients with disseminated forms of this disease but also in patients undergoing chemoradiotherapy or as induction therapy. Possibilities of adjuvant chemotherapy for cervical cancer are being studied. According to A.D.Kaprin and V.V. Starinskiy in 2013 in Russia, 32% of patients with newly diagnosed cervical cancer underwent only radiation therapy, 32%--combined or complex treatment, 27.3%--only surgery, and just 8.7%--chemoradiotherapy. PMID:26087600

  11. Understanding Chemotherapy

    MedlinePlus

    ... you may get chemotherapy before a peripheral blood stem cell transplant. Fill this section in with your doctor or nurse. I am getting chemo ... can be given in these forms: An IV (intravenously) A shot (injection) into a muscle or other part of your body A pill ...

  12. Inhibition of multiple vascular endothelial growth factor receptors (VEGFR) blocks lymph node metastases but inhibition of VEGFR-2 is sufficient to sensitize tumor cells to platinum-based chemotherapeutics.

    PubMed

    Sini, Patrizia; Samarzija, Ivana; Baffert, Fabienne; Littlewood-Evans, Amanda; Schnell, Christian; Theuer, Andreas; Christian, Sven; Boos, Anja; Hess-Stumpp, Holger; Foekens, John A; Setyono-Han, Buddy; Wood, Jeanette; Hynes, Nancy E

    2008-03-01

    Vascular endothelial growth factor receptors (VEGFR) have important roles in cancer, affecting blood and lymphatic vessel functionality as well as tumor cells themselves. We compared the efficacy of a VEGFR tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK), which targets the three VEGFRs, with blocking antibodies directed against VEGFR-2 (DC101) or VEGF-A (Pab85618) in a metastatic melanoma model. Although all inhibitors exerted comparable effects on primary tumor growth, only PTK/ZK significantly reduced lymph node metastasis formation. A comparable decrease in lymphatic vessel density following blockade of VEGFR-2 (DC101) or the three VEGFRs (PTK/ZK) was observed in the metastases. However, the functionality of lymphatics surrounding the primary tumor was more significantly disrupted by PTK/ZK, indicating the importance of multiple VEGFRs in the metastatic process. The antimetastatic properties of PTK/ZK were confirmed in a breast carcinoma model. B16/BL6 tumor cells express VEGF ligands and their receptors. Blockade of a VEGFR-1 autocrine loop with PTK/ZK inhibited tumor cell migration. Furthermore, the tumor cells also showed enhanced sensitivity to platinum-based chemotherapy in combination with PTK/ZK, indicating that autocrine VEGFRs are promoting tumor cell migration and survival. In summary, our results suggest that, in addition to blocking angiogenesis, combined inhibition of the three VEGFRs may more efficiently target other aspects of tumor pathophysiology, including lymphatic vessel functionality, tumor cell dissemination, survival pathways, and response to chemotherapeutic compounds. PMID:18316624

  13. Predicting response to chemotherapy with early-stage lung cancer.

    PubMed

    Rosell, Rafael; Taron, Miquel; Massuti, Bartomeu; Mederos, Nuria; Magri, Ignacio; Santarpia, Mariacarmela; Sanchez, Jose Miguel

    2011-01-01

    A recent meta-analysis of 11,107 patients with non-small cell lung cancer who had undergone surgical resection showed that the 5-year survival benefit of adjuvant chemotherapy was 4%, and that of adjuvant chemoradiotherapy was 5%. Two trials have shown a trend toward improved survival with adjuvant paclitaxel plus carboplatin. However, the benefit of adjuvant treatment remains suboptimal. We must distinguish between patients who will not relapse-and who can thus be spared adjuvant treatment-and those who will-for whom adjuvant treatment must be personalized. Several gene expression signatures, generally containing nonoverlapping genes, provide similar predictive information on clinical outcome, and a model combining several signatures did not perform better than did each of the signatures separately. The invasiveness gene signature, containing 186 genes, includes genes involved in the nuclear factor κB pathway, the RAS-mitogen-activated protein kinase pathway, and epigenetic control of gene expression. A 15-gene signature has identified JBR.10 patients who are more sensitive to adjuvant chemotherapy. PMID:21263267

  14. Adjuvant systemic treatment for individual patients with triple negative breast cancer.

    PubMed

    Oakman, Catherine; Moretti, Erica; Galardi, Francesca; Biagioni, Chiara; Santarpia, Libero; Biganzoli, Laura; Di Leo, Angelo

    2011-10-01

    Chemotherapy is the only evidence based adjuvant systemic treatment option in triple negative breast cancer (TNBC). Despite emerging results for targeted biological therapies for this subpopulation, lack of robust results does not currently support their use beyond the confines of a clinical trial. Conventional systemic chemotherapy remains the standard of care and is curative in a minority of patients. There is no defined standard chemotherapy and there is currently no robust, prospective, randomized data to advise different use of specific chemotherapy agents in TNBC as compared to non-TNBC. Data suggest high sensitivity to chemotherapy, however it is yet to be determined whether this increased sensitivity is agent/regimen specific or whether it reflects general chemosensitivity. This review will focus on systemic chemotherapy in early TNBC, particularly anthracyclines and platinums, and potential predictive tools to guide chemotherapy use. PMID:22015281

  15. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial

    PubMed Central

    Donskih, Roman; Jones, C. Michael; Nixon, Allen; Vidal, Maria J.; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-01-01

    Background. Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. Methods. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count <0.5 × 109/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin. Results. Baseline characteristics were well balanced. DSN was equivalent between groups at mean ± SD 1.36 ± 1.13 (LA-EP2006, n = 155) and 1.19 ± 0.98 (reference, n = 153) in cycle 1. With a treatment difference (reference minus LA-EP2006) of −0.16 days (90% CI −0.36 to 0.04; 95% CI −0.40 to 0.08), LA-EP2006 was equivalent to reference pegfilgrastim. Secondary efficacy parameters were similar between groups during cycle 1 and across cycles. Safety profiles were also similar between groups. No neutralizing antibodies against pegfilgrastim, filgrastim, or polyethylene glycol were detected. Conclusion. LA-EP2006 and reference pegfilgrastim were therapeutically equivalent and comparable regarding efficacy and safety in the prevention of neutropenia in patients with early-stage breast cancer receiving TAC. Implications for Practice: The

  16. [New options in adjuvant endocrine therapy in breast cancer].

    PubMed

    Saltel-Fulero, Aurélien; Donnadieu, Anne; Leman-Detours, Solenne; Cottu, Paul

    2016-01-01

    Endocrine therapy is a compulsory step in the adjuvant management of early breast cancer expressing the estrogen receptor, by reducing as much as possible serum and tissue levels of estrogens. Tamoxifen is the standard therapy for non-menopausal women. Ovarian function suppression, in addition to exemestane or tamoxifen, could be an alternative option for young women at high risk of recurrence and non menopausal after adjuvant or neo-adjuvant chemotherapy. Recent studies show a trend for improvement of overall survival and disease-free-survival with aromatase inhibitors among postmenopausal women. However, safety of aromatase inhibitors is controversial and adverse events may lead to switch for tamoxifen with no loss of efficacy. Extension therapy by tamoxifen or aromatase inhibitor after five years of tamoxifen and for a total duration of ten years significantly improves overall survival. There is to date no data supporting the extension therapy after five years of aromatase inhibitor. PMID:26675809

  17. Adjuvant Therapy for Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad A.

    2012-01-01

    Estimates from the U.S. Surveillance, Epidemiology, and End Results (SEER) registry suggest that melanoma incidence will reach 70,230 in 2011, of which 8,790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society. High-dose interferon-α2b is the only agent approved for adjuvant therapy of melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However toxicity affects compliance and current research is focusing upon biomarkers that may allow selection of patients with greater likelihood of response, and exploring new agents either singly or in combination that may improve upon the benefit of IFN. In this article, we review the data for the adjuvant therapy of malignant melanoma - focusing on the results obtained with various regimens testing the several formulations of interferon-α2, and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, and raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway. PMID:22453021

  18. Laser vaccine adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  19. HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy

    PubMed Central

    Zhao, Wei; Dong, Shuang; Duan, Bensong; Chen, Ping; Shi, Lei; Gao, Hengjun; Qi, Haizhi

    2015-01-01

    Accumulating evidence suggests that long non-coding RNA (lncRNA) HOTAIR participates in many types of cancer such as gastric cancer and may confer malignant phenotype to tumor cells. Fluorouracil and platinum combination chemotherapy is the first line therapy for gastric cancer. However, it is still unknown whether HOTAIR influences the outcome of cancer patients treated with chemotherapy. This study aimed to evaluate the association of HOTAIR expression with the prognosis of patients with advanced gastric adenocarcinoma (GA) receiving fluorouracil and platinum based chemotherapy. We examined the levels of HOTAIR in 168 GA samples using quantitative real-time PCR and analyzed its relationship with clinical features and prognosis of patients with advanced GA treated with fluorouracil and platinum based chemotherapy. Compared with paracancerous tissues, HOTAIR was significantly upregulated in GA tissues, especially in more advanced cases. High HOTAIR expression was an independent poor prognostic factor for patients with advanced GA. Further stratification analyses revealed that the association between HOTAIR expression and survival in patients with advanced GA remained significant in the subgroup of patients with TNM stages IIIA and IIIB, poorly differentiated, and smaller tumors. In conclusion, our results provide first evidence that HOTAIR may be served as a biomarker that predicts which patient with advanced GA will benefit from fluorouracil and platinum combination chemotherapy. PMID:26328013

  20. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance.

    PubMed

    Pinato, David J; Graham, Janet; Gabra, Hani; Sharma, Rohini

    2013-04-01

    Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered "platinum resistant". In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled "dose-dense" platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance. PMID:22595680

  1. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  2. What make differences in the outcome of adjuvant treatments for resected gastric cancer?

    PubMed Central

    Nakajima, Toshifusa; Fujii, Masashi

    2014-01-01

    After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery. PMID:25206264

  3. Adjuvant Immunotherapy of Melanoma, and Development of New Approaches Using the Neo- Adjuvant Approach in Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad

    2013-01-01

    Melanoma is the third most common skin cancer but the leading cause of death from cutaneous malignancies. While early-stage disease is frequently cured by surgical resection with excellent long-term survival, patients with deeper primary lesions (AJCC stage IIB-C) and those with microscopic (IIIA) or clinically evident regional lymph node or in-transit metastases (IIIB-C) have an increased risk of relapse and death–the latter approaching 70% or more at 5 years. In patients at high-risk of recurrence/metastases, adjuvant therapy with high-dose interferon alpha-2b (HDI) following definitive surgical resection has been shown to improve relapse free and overall survival. Neo-adjuvant chemotherapy and/or radiotherapy have offered the prospect to improve regional recurrence risk and overall survival in several solid tumors. The advent of effective new molecularly targeted therapies for metastatic disease and new immunotherapies that overcome checkpoints of immune response have augmented the range of new options that are in current trial evaluation to determine their role as potential adjuvant therapies, alone and in combination with one another, and the established modality of IFNα. The differential characteristics of the host immune response between early and advanced melanoma provide a strong mechanistic rationale for the use of neo-adjuvant immunotherapeutic approaches in melanoma, and the opportunity to evaluate the mechanism of action suggest neoadjuvant trial evaluation for each of the new candidate agents and combinations of interest. Several neo-adjuvant trials have been conducted in the phase II setting, which have illuminated the mechanism of IFNα, as well as providing insight to the effects of anti-CTLA4 blocking antibodies. These agents (anti-CTLA4 blocking antibody ipilimumab [BMS], and BRAF inhibitor vemurafenib [Genentech]) are likely to be followed by other immunotherapies that may overcome the PD-1 checkpoint (anti-PD1 [BMS, Merck, Curetech] and anti

  4. Predictive role of HER2/neu, topoisomerase-II-alpha, and tissue inhibitor of metalloproteinases (TIMP-1) for response to adjuvant taxane-based chemotherapy in patients with intermediate-risk breast cancer: results from the WSG-AGO EC-Doc trial.

    PubMed

    Erber, Ramona; Gluz, Oleg; Brünner, Nils; Kreipe, Hans Heinrich; Pelz, Enrico; Kates, Ronald; Bartels, Annette; Huober, Jens; Mohrmann, Svjetlana; Moustafa, Zehra; Liedtke, Cornelia; Möbus, Volker; Augustin, Doris; Thomssen, Christoph; Jänicke, Fritz; Kiechle, Marion; Kuhn, Walther; Nitz, Ulrike; Harbeck, Nadia; Hartmann, Arndt

    2015-04-01

    Taxane-anthracycline-based adjuvant chemotherapy is standard of care in patients with node-positive breast cancer (BC) but is also associated with severe side effects and significant costs. It is yet unclear, which biomarkers would predict benefit from taxanes and/or general chemoresistance. In this study, we investigate a large cohort of patients with intermediate-risk BC treated within the WSG EC-DOC Trial for the predictive impact of topoisomerase-II-alpha, HER2/neu, and TIMP-1. Tumor tissue was available in a representative cohort of 772 cases of the WSG EC-DOC Trial collective which compared 4xEC-4xDoc versus 6xCEF/CMF. In addition to hormone receptor status and Ki-67, HER2/neu+ and topoisomerase-II-alpha status using fluorescence in situ hybridisation (FISH) and immunohistochemistry, TIMP-1 using immunohistochemistry, and aneuploidy of chromosome 17 using FISH were evaluated and correlated with outcome and taxane benefit. There was significant superiority of EC-Doc over CEF regarding 5-year DFS (90 vs. 80 %, respectively, p = 0.006) particularly in patient subgroups defined by HR+, HER2/neu+, high proliferation (i.e., Ki-67 ≥ 20 %), patient age >50 years old and normal chromosome 17 status, high TIMP-1 and low topoisomerase-II-alpha protein expression. Significant prognostic factors in multivariate analysis were EC-Doc therapy (HR = 0.61; 95 %CI 0.38-0.986), age <50 years old (HR = 1.682; 95 %CI 1.025-2.579), centrally assessed grade 3 (HR = 4.657; 95 %CI 1.809-11.989), and high Ki-67 (HR = 2.232; 95 %CI 1.209-4.121). Interestingly, we observed a significant interaction between treatment arm (EC-Doc vs. CEF) and high topoisomerase-II-alpha protein expression (HR = 0.427; 95 %CI 0.203-0.900) in multivariate interaction analysis. Despite of univariate predictive effect of HER2/neu status among other factors only topoisomerase-II-alpha protein expression was associated with significant benefit from EC-Doc compared to CEF by multivariate interaction analysis

  5. An Unusual Cause of Subacute Headache in a Patient Undergoing Chemotherapy for Advanced Testicular Nonseminomatous Germ Cell Tumour

    PubMed Central

    Porfiri, Emilio

    2016-01-01

    Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short-duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment. PMID:27200199

  6. Surgical controversies in the management of post-chemotherapy nonretroperitoneal residual disease in metastatic nonseminomatous germ cell tumors

    PubMed Central

    Pandey, Durgatosh; Garg, Pankaj Kumar; Ray, Mukur Dipi; Mishra, Ashutosh

    2016-01-01

    Following the advent of platinum-based chemotherapy, Surgery, excepting orchidectomy, has become an adjunct treatment in the management of metastatic non-seminomatous germ cell tumors (NSGCT). Role of surgery comes into play in metastatic NSGCT when residual disease persists following standard chemotherapy. Surgical excision of all post chemotherapy residual disease at all places, whenever surgically feasible with acceptable morbidity and mortality, should be undertaken. As histopathological examination of the excised postchemotherapy residue shows only necrosis and fibrosis in significant number of patients; surgical exercise in this group of patients seems futile and unwarranted retrospectively. This issue becomes more contentious when surgeons are confronted with multiple nonretroperitoneal post chemotherapy residues. This article aims to deal with the management of postchemotherapy nonretroperitoneal residues in metastatic NSGCT. PMID:27169116

  7. High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation.

    PubMed

    Gorodnova, Tatiana V; Sokolenko, Anna P; Ivantsov, Alexandr O; Iyevleva, Aglaya G; Suspitsin, Evgeny N; Aleksakhina, Svetlana N; Yanus, Grigory A; Togo, Alexandr V; Maximov, Sergey Ya; Imyanitov, Evgeny N

    2015-12-28

    Preoperative therapy provides an advantage for clinical drug assessment, as it involves yet untreated patients and facilitates access to the post-treatment biological material. Testing for Slavic founder BRCA mutations was performed for 225 ovarian cancer (OC) patients, who were treated by platinum-based neoadjuvant therapy. 34 BRCA1 and 1 BRCA2 mutation carriers were identified. Complete clinical response was documented in 12/35 (34%) mutation carriers and 8/190 (4%) non-carriers (P = 0.000002). Histopathologic response was observed in 16/35 (46%) women with the germ-line mutation versus 42/169 (25%) patients with the wild-type genotype (P = 0.02). Somatic loss of heterozygosity (LOH) for the remaining wild-type BRCA1 allele was detected only in 7/24 (29%) post-neoadjuvant therapy residual tumor tissues as compared to 9/11 (82%) BRCA1-associated OC, which were not exposed to systemic treatment before the surgery (P = 0.009). Furthermore, comparison of pre- and post-treatment tumor material obtained from the same patients revealed restoration of BRCA1 heterozygosity in 2 out of 3 sample pairs presenting with LOH at diagnosis. The obtained data confirm high sensitivity of BRCA-driven OC to platinating agents and provide evidence for a rapid selection of tumor cell clones without LOH during the course of therapy. PMID:26342406

  8. Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-09-12

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Tumor; Ovarian Seromucinous Carcinoma; Ovarian Serous Tumor; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  9. Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer

    PubMed Central

    Garon, Edward B.; Christofk, Heather R.; Hosmer, Wylie; Britten, Carolyn D; Bahng, Agnes; Crabtree, Matthew J; Hong, Candice Sun; Kamranpour, Naeimeh; Pitts, Sharon; Kabbinavar, Fairooz; Patel, Cecil; von Euw, Erika; Black, Alexander; Michelakis, Evangelos D.; Dubinett, Steven M.; Slamon, Dennis J.

    2014-01-01

    Objectives Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage NSCLC. Materials and Methods This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV non-small cell lung cancer (NSCLC) or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions. Results and Conclusions Under normoxic conditions in vitro, single agent IC50 was > 2 mM for all evaluated cell lines. Synergy with cisplatin was seen in some cell lines under hypoxic conditions. In the clinical trial, after seven patients were enrolled, the study was closed based on safety concerns. The only breast cancer patient had stable disease after 8 weeks, quickly followed by progression in the brain. Two patients withdrew consent within a week of enrollment. Two patients had disease progression prior to the first scheduled scans. Within one week of initiating DCA, one patient died suddenly of unknown cause, and one experienced a fatal pulmonary embolism. We conclude that patients with previously treated advanced NSCLC did not benefit from oral DCA. In the absence of a larger controlled trial, firm conclusions regarding the association between these adverse events and DCA are unclear. Further development of DCA should be in patients with longer life expectancy, in whom sustained therapeutic levels can be achieved, and potentially in combination with cisplatin. PMID:24442098

  10. Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy.

    PubMed

    Hashiguchi, Yasunori; Kasai, Mari; Fukuda, Takeshi; Ichimura, Tomoyuki; Yasui, Tomoyo; Sumi, Toshiyuki

    2015-11-01

    Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24-84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1-12 days) and 3.4 days (range 1-9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P<0.0001), less than five previous chemotherapy cycles (P=0.02), disseminated disease (P=0.03), platinum-based regimens (P<0.0001), taxane-containing regimens (P<0.0001), and combined therapy (P<0.0001). Febrile neutropenia was associated with poor performance status (P<0.0001), no previous chemotherapy (P<0.05), disseminated disease (P<0.0001), and distant metastatic disease (P=0.03). Neither chemotherapy-induced neutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy. PMID:26267078

  11. Capecitabine Induced Multifocal Leukoencephalopathy: Do We Have Always to Switch off the Chemotherapy?

    PubMed

    Bougea, Anastasia; Voskou, Panagiota; Kilidireas, Constantinos; Andreadou, Elisabeth

    2016-01-01

    Capecitabine is a well tolerated and safe 5-fluorouracil agent for adjuvant, neoadjuvant chemotherapy or metastatic cases. Neurological side effects require discontinuation of chemotherapy. We report this unique case of a 50-year-old female, who presented an isolated episode of dysarthria and ataxia under bevacizumab, capecitabine, and oxaliplatin treatment due to reversible multifocal leukoencephalopathy that did not recur after readministration of chemotherapy. PMID:26966603

  12. Impact of Adjuvant Radiotherapy on Survival after Pancreatic Cancer Resection: An Appraisal of Data from the National Cancer Data Base

    PubMed Central

    Kooby, David A.; Gillespie, Theresa W.; Liu, Yuan; Byrd-Sellers, Johnita; Landry, Jerome; Bian, John; Lipscomb, Joseph

    2016-01-01

    Purpose The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB). Methods Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias. Results From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61–0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93–1.18) and NoAdjuvant (index). Conclusions Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC. PMID:23771249

  13. Genetic polymorphisms of DNA repair pathways influence the response to chemotherapy and overall survival of gastric cancer.

    PubMed

    Zhou, Jing; Liu, Zhi-yue; Li, Cun-bao; Gao, Shang; Ding, Li-hong; Wu, Xin-lin; Wang, Zhao-yang

    2015-04-01

    We aimed to evaluate the clinical response to platinum-based chemotherapy and treatment outcome of gastric cancer patients in the present of ERCC1, ERCC2, NBN, RAD51, and XRCC3 gene polymorphisms. A number of 415 patients of gastric cancer that received platinum-based chemotherapy were enrolled in the present study. The presence of ERCC1 rs11615 and rs2298881, ERCC2 rs1799793 and rs13181, NBN rs1805794, rs709816, and RAD51 rs1801321 and XRCC3 rs1799794 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Conditional regression analysis identified that CC genotype of ERCC1 rs11615 and AA genotype of ERCC2 rs1799793 was associated with a better response to chemotherapy in gastric cancer patients, and the odds ratio (ORs)(95% confidence interval (CI)) were 2.70(1.33-5.70) and 3.12(1.52-6.84), respectively. By the Cox analysis, the CC genotype of ERCC1 rs11615, AA genotype of ERCC2 rs1799793, and CC genotype of NBN rs1805794 were significantly associated with a longer overall survival (OS) of gastric cancer. In conclusion, our results suggest that ERCC1 rs11615, ERCC2 rs1799793, and NBN rs1805794 polymorphisms in the DNA repair pathways may influence the response to chemotherapy and OS of gastric cancer. PMID:25542228

  14. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... cancer Next Topic Targeted therapy for thyroid cancer Chemotherapy for thyroid cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  15. Types of chemotherapy

    MedlinePlus

    Chemotherapy is the use of medicine to treat cancer. Chemotherapy kills cancer cells. It may be used to ... people are treated with a single type of chemotherapy. But often, people get more than one type ...

  16. Adjuvant Therapy Trials.

    PubMed

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

  17. The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone

    PubMed Central

    Nutter, Benjamin; Abdul-Karim, Fadi; Amarnath, Sudha; Rose, Peter G

    2016-01-01

    Objective To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy. Methods Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used. Results Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I–II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy. Conclusion In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome. PMID:26463437

  18. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

    PubMed Central

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah

    2016-01-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  19. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy.

    PubMed

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah; Kim, Kwang Ho

    2016-03-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  20. Carbohydrate-based immune adjuvants

    PubMed Central

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  1. Adjuvant therapy for gastric cancer: What have we learned since INT0116?

    PubMed Central

    Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

    2015-01-01

    Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease. PMID:25852269

  2. Adjuvant Therapy: Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad; Kirkwood, John M.

    2011-01-01

    With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. PMID:22220281

  3. A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

    PubMed

    Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Battaglia, Giorgio; Bocus, Paolo; Castoro, Carlo; Cagol, Matteo; Chiarion-Sileni, Vanna; Ruol, Alberto; Amadori, Alberto; Saggioro, Daniela

    2016-05-01

    Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management. PMID:26772957

  4. Chemotherapy for Patients with BRCA1 and BRCA2-Mutated Ovarian Cancer: Same or Different?

    PubMed

    Tan, David S P; Kaye, Stanley B

    2015-01-01

    Retrospective studies have shown an improved prognosis, higher response rates to platinum-containing regimens, and longer treatment-free intervals between relapses in patients with BRCA 1 and BRCA 2 (BRCA1/2)-mutated ovarian cancer (BMOC) compared with patients who are not carriers of this mutation. These features of BMOC are attributed to homologous-recombination repair (HR) deficiency in the absence of BRCA1/2 function, which results in an impaired ability of tumor cells to repair platinum-induced double-strand breaks (DSBs), thereby conferring increased chemosensitivity and increased sensitivity to poly(ADP-ribose) polymerase (PARP) enzyme inhibition and other DNA-damaging chemotherapeutic agents such as pegylated liposomal doxorubicin (PLD). Therefore, the chemotherapeutic approach for patients with BMOC should focus on treatment with platinum-based chemotherapy at first-line and recurrent-disease settings and measures to increase the platinum-free interval following early platinum-resistant relapse (i.e., progression-free survival of less than 6 months from last platinum-based chemotherapy) by using nonplatinum cytotoxic agents, with the aim of reintroducing platinum again at a later date. The role of first-line intraperitoneal platinum-based therapy in the specific context of BMOC also merits further analysis. Other than platinum, alternative DNA-damaging agents (including PLD and trabectedin) also may have a therapeutic role in patients with recurrent BMOC. The recent approval of olaparib for clinical use in Europe and the United States will also affect chemotherapeutic strategies for these patients. Further work to clarify the precise relationship between BRCA1/2 mutation genotype and clinical phenotype is crucial to delineating the optimal therapeutic choices in the future for patients with BMOC. PMID:25993149

  5. Association Between Geographic Access to Cancer Care, Insurance, and Receipt of Chemotherapy: Geographic Distribution of Oncologists and Travel Distance

    PubMed Central

    Lin, Chun Chieh; Bruinooge, Suanna S.; Kirkwood, M. Kelsey; Olsen, Christine; Jemal, Ahmedin; Bajorin, Dean; Giordano, Sharon H.; Goldstein, Michael; Guadagnolo, B. Ashleigh; Kosty, Michael; Hopkins, Shane; Yu, James B.; Arnone, Anna; Hanley, Amy; Stevens, Stephanie; Hershman, Dawn L.

    2015-01-01

    Purpose Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy. Patients and Methods Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics. Results Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P = .009) or ≥ 250 miles (OR, 0.36; P < .001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P = .77). When stratifying analyses by insurance status, non–privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P = .03). Conclusion Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment. PMID:26304878

  6. Have adjuvant tyrosine kinase inhibitors lost their shine?

    PubMed Central

    Sabari, Joshua K.

    2016-01-01

    Despite broad advances in molecularly targeted therapies, lung cancer remains the leading cause of cancer related mortality in the United States. Epidermal growth factor receptor (EGFR) mutations occur in approximately 17% of advanced non-small cell lung cancer (NSCLC) in the US population. The remarkable efficacy of small-molecule EGFR tyrosine kinase inhibitors (TKIs) in this unique subset of patients has revolutionized the therapeutic approach to lung cancer. The success of these agents in the metastatic setting leads to the logical question of what role these drugs may have in the adjuvant setting for patients with earlier stage disease. RADIANT, an international randomized, double-blind, placebo controlled phase III study in patients with completely resected stage IB to IIIA NSLC whose tumors expressed EGFR by IHC and EGFR amplification by FISH, attempted to answer the question of whether erlotinib would improve disease free survival and overall survival in the adjuvant setting. While RADIANT does not conclude for or against adjuvant use of EGFR-TKIs, all data points towards benefit in a selected population. As clinicians, we must continue to enroll to potentially practice changing therapeutic neoadjuvant and adjuvant chemotherapy studies internationally. PMID:27568486

  7. Have adjuvant tyrosine kinase inhibitors lost their shine?

    PubMed

    Sabari, Joshua K; Chaft, Jamie E

    2016-08-01

    Despite broad advances in molecularly targeted therapies, lung cancer remains the leading cause of cancer related mortality in the United States. Epidermal growth factor receptor (EGFR) mutations occur in approximately 17% of advanced non-small cell lung cancer (NSCLC) in the US population. The remarkable efficacy of small-molecule EGFR tyrosine kinase inhibitors (TKIs) in this unique subset of patients has revolutionized the therapeutic approach to lung cancer. The success of these agents in the metastatic setting leads to the logical question of what role these drugs may have in the adjuvant setting for patients with earlier stage disease. RADIANT, an international randomized, double-blind, placebo controlled phase III study in patients with completely resected stage IB to IIIA NSLC whose tumors expressed EGFR by IHC and EGFR amplification by FISH, attempted to answer the question of whether erlotinib would improve disease free survival and overall survival in the adjuvant setting. While RADIANT does not conclude for or against adjuvant use of EGFR-TKIs, all data points towards benefit in a selected population. As clinicians, we must continue to enroll to potentially practice changing therapeutic neoadjuvant and adjuvant chemotherapy studies internationally. PMID:27568486

  8. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine.

    PubMed

    Podda, A

    2001-03-21

    Elderly people and subjects with underlying chronic diseases are at increased risk for influenza and related complications. Conventional influenza vaccines provide only limited protection in the elderly population. In order to enhance the immune response to influenza vaccines, several adjuvants have been evaluated. Among these, an oil in water adjuvant emulsion containing squalene, MF59, has been combined with subunit influenza antigens and tested in clinical trials in comparison with non-adjuvanted conventional vaccines. Data from a clinical database of over 10000 elderly subjects immunised with this adjuvanted vaccine (Fluad, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons. Immunogenicity analyses demonstrate a consistently higher immune response with statistically significant increases of postimmunisation geometric mean titres, and of seroconversion and seroprotection rates compared to non-adjuvanted subunit and split influenza vaccines, particularly for the A/H3N2 and the B strains. The higher immunogenicity profile of the MF59-adjuvanted vaccine is maintained also after subsequent immunisations. An even higher adjuvant effect was shown in subjects with low pre-immunisation titre and in those affected by chronic underlying diseases. In conclusion, the addition of MF59 to subunit influenza vaccines enhances significantly the immune response in elderly subjects without causing clinically important changes in the safety profile of the influenza vaccine. PMID:11257408

  9. Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer

    PubMed Central

    2013-01-01

    Background Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. Methods The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with standard platinum-based chemotherapy. Twelve patient tumours demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumours from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using an Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumours from the resistant group and the sensitive group. Results Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NF κB/ERK gene signalling networks. Conclusions This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. In addition, our

  10. Adjuvants and delivery systems for antifungal vaccines: current state and future developments.

    PubMed

    Portuondo, Deivys Leandro F; Ferreira, Lucas S; Urbaczek, Ana C; Batista-Duharte, Alexander; Carlos, Iracilda Z

    2015-01-01

    Mycoses are gaining increasing attention in modern medicine because of the increase in diseases associated with opportunistic fungal infections. Despite the recognized role of the immune system in the control of fungal infections, no antifungal vaccines are currently licensed for use in humans. However, numerous vaccine candidates are being developed in many laboratories, as proof of the renewed interest in integrating or replacing chemotherapy with vaccines to reduce antibiotic use and consequently limit drug resistance and toxicity. In the effort to use safer and simpler fungal antigens for vaccinations, adjuvants have become relevant as immunostimulators to elicit successful protective immune responses. To address the relevant role of adjuvants as determinants in the balance of vaccine efficacy and safety, an updated and critical review of the adjuvants used in preclinical antifungal vaccines is presented, and prospective trends are addressed. Selected recent papers and other historically relevant and innovative strategies using adjuvants in experimental fungal vaccines are highlighted. PMID:25362733

  11. Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

    PubMed

    Nio, Kenta; Higashi, Daijiro; Kumagai, Hozumi; Arita, Shuji; Shirakawa, Tsuyoshi; Nakashima, Koji; Shibata, Yoshihiro; Esaki, Motohiro; Manabe, Tatsuya; Nagai, Shuntaro; Ueki, Takashi; Nakano, Michitaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Hirahashi, Minako; Oda, Yoshinao; Esaki, Taito; Mitsugi, Kenji; Futami, Kitaro; Akashi, Koichi; Baba, Eishi

    2016-06-01

    Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P<0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis. PMID:26771865

  12. [Laparoscopic surgery and adjuvant therapy for colon cancer].

    PubMed

    Kubicka, Stefan; Geissler, Michael; Bruch, Hans-Peter; Trarbach, Tanja

    2009-01-01

    At present, about 10% of all oncological procedures in the colon are carried out laparoscopically. Acceptance is increasing. After successful R0 resection, the rule for stage III patients is: adjuvant therapy is indicated regardless of age. Regimens containing oxaliplatin should be used. If there are contraindications for oxaliplatin, then fluoropyrimidine monotherapy is indicated, with oral fluoropyrimidines (capecitabine) being given precedence over infusional schemes. The use of 5-FU bolus regimens is regarded as obsolete. For stage II, the following applies: If an adjuvant chemotherapy is planned in these patients on the basis of the QUASAR data, then fluoropyrimidine monotherapy (e. g. capecitabine) can be given. Since patients whose tumours show a high frequency of microsatellite instability (MSI) do not benefit from a fluoropyrimidine monotherapy, the MSI status should be determined before choosing therapy. PMID:19546595

  13. Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies

    PubMed Central

    Cidon, E. Una

    2016-01-01

    Cholangiocarcinoma is a very heterogeneous and rare group of neoplasms originating from the perihilar, intra-, or extrahepatic bile duct epithelium. It represents only 3% of gastrointestinal cancers, although their incidence is increasing as its mortality increases. Surgical resection is the only potentially curative option, but unfortunately the resectability rate is low. Overall, these malignancies have got a very poor prognosis with a five-year survival rate of 5–10%. Although the five-year survival rate increases to 25–30% in the cases amenable to surgery, only 10–40% of patients present with resectable disease. Therefore, it is necessary to optimize the benefit of adjuvant strategies after surgery to increase the rate of curability. This study reviewed the role of adjuvant chemotherapy in resectable bile duct cancers. PMID:27199577

  14. Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study

    PubMed Central

    2014-01-01

    Background Improvement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence. Methods/Design Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat. Discussion Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We

  15. Development of XFCT imaging strategy for monitoring the spatial distribution of platinum-based chemodrugs: Instrumentation and phantom validation

    SciTech Connect

    Kuang Yu; Pratx, Guillem; Bazalova, Magdalena; Qian Jianguo; Meng Bowen; Xing Lei

    2013-03-15

    Purpose: Developing an imaging method to directly monitor the spatial distribution of platinum-based (Pt) drugs at the tumor region is of critical importance for early assessment of treatment efficacy and personalized treatment. In this study, the authors investigated the feasibility of imaging platinum (Pt)-based drug distribution using x-ray fluorescence (XRF, a.k.a. characteristic x ray) CT (XFCT). Methods: A 5-mm-diameter pencil beam produced by a polychromatic x-ray source equipped with a tungsten anode was used to stimulate emission of XRF photons from Pt drug embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The x-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used for the K-shell XRF peak isolation and sinogram generation for Pt. The distribution and concentration of Pt were reconstructed with an iterative maximum likelihood expectation maximization algorithm. The capability of XFCT to multiplexed imaging of Pt, gadolinium (Gd), and iodine (I) within a water phantom was also investigated. Results: Measured XRF spectrum showed a sharp peak characteristic of Pt with a narrow full-width at half-maximum (FWHM) (FWHM{sub K{alpha}1}= 1.138 keV, FWHM{sub K{alpha}2}= 1.052 keV). The distribution of Pt drug in the water phantom was clearly identifiable on the reconstructed XRF images. Our results showed a linear relationship between the XRF intensity of Pt and its concentrations (R{sup 2}= 0.995), suggesting that XFCT is capable of quantitative imaging. A transmission CT image was also obtained to show the potential of the approach for providing attenuation correction and morphological information. Finally, the distribution of Pt, Gd, and I in the water phantom was clearly identifiable in the reconstructed images from XFCT multiplexed imaging. Conclusions: XFCT is a promising modality for monitoring

  16. Development of XFCT imaging strategy for monitoring the spatial distribution of platinum-based chemodrugs: Instrumentation and phantom validation

    PubMed Central

    Kuang, Yu; Pratx, Guillem; Bazalova, Magdalena; Qian, Jianguo; Meng, Bowen; Xing, Lei

    2013-01-01

    Purpose: Developing an imaging method to directly monitor the spatial distribution of platinum-based (Pt) drugs at the tumor region is of critical importance for early assessment of treatment efficacy and personalized treatment. In this study, the authors investigated the feasibility of imaging platinum (Pt)-based drug distribution using x-ray fluorescence (XRF, a.k.a. characteristic x ray) CT (XFCT). Methods: A 5-mm-diameter pencil beam produced by a polychromatic x-ray source equipped with a tungsten anode was used to stimulate emission of XRF photons from Pt drug embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The x-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used for the K-shell XRF peak isolation and sinogram generation for Pt. The distribution and concentration of Pt were reconstructed with an iterative maximum likelihood expectation maximization algorithm. The capability of XFCT to multiplexed imaging of Pt, gadolinium (Gd), and iodine (I) within a water phantom was also investigated. Results: Measured XRF spectrum showed a sharp peak characteristic of Pt with a narrow full-width at half-maximum (FWHM) (FWHMKα1 = 1.138 keV, FWHMKα2 = 1.052 keV). The distribution of Pt drug in the water phantom was clearly identifiable on the reconstructed XRF images. Our results showed a linear relationship between the XRF intensity of Pt and its concentrations (R2 = 0.995), suggesting that XFCT is capable of quantitative imaging. A transmission CT image was also obtained to show the potential of the approach for providing attenuation correction and morphological information. Finally, the distribution of Pt, Gd, and I in the water phantom was clearly identifiable in the reconstructed images from XFCT multiplexed imaging. Conclusions: XFCT is a promising modality for monitoring the spatial distribution of

  17. Time-to-administration in postoperative chemotherapy for colorectal cancer: does minimally-invasive surgery help?

    PubMed

    Amore Bonapasta, Stefano; Checcacci, Paolo; Guerra, Francesco; Mirasolo, Vita M; Moraldi, Luca; Ferrara, Angelo; Annecchiarico, Mario; Coratti, Andrea

    2016-06-01

    The optimal delay in the start of chemotherapy following rectal cancer surgery has not yet been identified. However, postponed adjuvant therapy has been proven to be connected with a significant survival detriment. We aimed to investigate whether the time to initiation of adjuvant treatment can be influenced by the application of minimally invasive surgery rather than traditional open surgery. By comprehensively evaluating the available inherent literature, several factors appear to be associated with delayed postoperative chemotherapy. Some of them are strictly related to surgical short-term outcomes. Laparoscopy results in shortened length of hospital stay, reduced surgical morbidity and lower rate of wound infection compared to conventional surgery. Probably due to such advantages, the application of minimally-invasive surgery to treat rectal malignancies seems to impact favorably the possibility to start adjuvant chemotherapy within an adequate timeframe following surgical resection, with potential improvement in patient survival. PMID:26976732

  18. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    SciTech Connect

    Not Available

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy.

  19. Using antimicrobial adjuvant therapy in cancer treatment: a review

    PubMed Central

    2012-01-01

    Recent clinical and pre-clinical data demonstrate that adjuvant antimicrobial therapy is beneficial in cancer treatment. There could be several reasons for this effect, which include treating cancer associated bacteria and viruses, prophylaxis of post-chemotherapy infections due to immunosuppression, and antiproliferative effect of certain antimicrobials. Targeting cancer associated viruses and bacteria with antimicrobial agents is currently used for gastric, cervical, hematopoietic, liver and brain cancer. However this treatment is effective only in combination with conventional therapies. Antimicrobials can also have a direct antiproliferative and cytotoxic effect, and can cause apoptosis. Moreover, some antimicrobials are known to be helpful in overcoming side effects of drugs commonly used in cancer treatment. Chemotherapy related bacteremia and neutropenia can be overcome by the appropriately timed use of antimicrobials. This review summarizes the data on the effects of antivirals and antibiotics on cancer treatment and describes their mechanisms. PMID:23164412

  20. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  1. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  2. Astragalus-containing Traditional Chinese Medicine, with and without prescription based on syndrome differentiation, combined with chemotherapy for advanced non-small-cell lung cancer: a systemic review and meta-analysis

    PubMed Central

    Wang, S.F.; Wang, Q.; Jiao, L.J.; Huang, Y.L.; Garfield, D.; Zhang, J.; Xu, L.

    2016-01-01

    Objective Traditional Chinese Medicine (tcm) is used in China as part of the treatment for non-small-cell lung cancer (nsclc) and often includes prescription of herbal therapy based on syndrome differentiation. Studies of various Astragalus-based Chinese medicines combined with platinum-based chemotherapy in the treatment of lung cancer are popular in East Asia, particularly in China. The aim of the present study was to perform a systematic review and meta-analysis comparing platinum-based chemotherapy alone with platinum-based chemotherapy plus Astragalus-based Chinese botanicals, with and without prescription based on syndrome differentiation, as first-line treatment for advanced nsclc. Methods We searched the Chinese Biomedical Literature database, the China National Knowledge Internet, the VIP Chinese Science and Technology Periodicals Database, PubMed, embase, the Cochrane databases, and abstracts presented at meetings of the American Society of Clinical Oncology, the World Conference on Lung Cancer, the European Society for Medical Oncology, and the Chinese Society of Clinical Oncology for all eligible studies. Endpoints were overall survival; 1-year, 2-year, and 3-year survival rates; performance status; overall response rate; and grade 3 or 4 adverse events. Subgroup analyses based on herbal formulae individualized using syndrome differentiation or on oral or injection patent medicines were performed using the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.) and a fixed-effects or random-effects model in case of heterogeneity. Results are expressed as a hazard ratio (hr) or relative risk (rr), with corresponding 95% confidence intervals (cis). Results Seventeen randomized studies with scores on the Jadad quality scale of 2 or more, representing 1552 patients, met the inclusion criteria. Compared with platinum-based chemotherapy alone, the addition of Astragalus-based tcm to chemotherapy was associated with significantly

  3. High Risk Stage 2 and Stage 3 Colon Cancer, Predictors of Recurrence and Effect of Adjuvant Therapy in a Nonselected Population

    PubMed Central

    van Eeghen, Elmer E.; Bakker, Sandra D.; van Bochove, Aart; Loffeld, Ruud J. L. F.

    2015-01-01

    Patients with stage 2 and stage 3 colon cancer often are treated with adjuvant chemotherapy. However, patients seen in daily practice have more comorbidity than those enrolled in clinical trials. This study aims to evaluate prognostic factors for recurrence and to ascertain the benefit of adjuvant chemotherapy on recurrence-free survival (RFS) of patients in a nonselected population. Furthermore, the impact of relative dose intensity (RDI) of adjuvant therapy on RFS is examined. Chart review was performed for 243 consecutive patients diagnosed and treated at a single center for stage 2 and stage 3 colon cancer from 2002 to 2008. Adjuvant chemotherapy was administered to 66 patients. Median overall survival (OS) was 5.84 years and median RFS was 5.37 years. For stage 2 disease, patients treated with or without adjuvant therapy had a median RFS of 5.49 and 5.73, respectively (p = ns). For stage 3 disease, median RFS rates were 5.08 and 1.19, respectively (p = 0.084). Overall RDI of oxaliplatin based chemotherapy higher than median was associated with increased RFS (p = 0.045). In conclusion, adjuvant therapy did not significantly increase recurrence-free survival. This could be the result of comorbidity in patients. Relative dose intensity of oxaliplatin based therapy is associated with RFS.

  4. Advances in adjuvant systemic therapy for non-small-cell lung cancer.

    PubMed

    Leong, David; Rai, Rajat; Nguyen, Brandon; Lee, Andrew; Yip, Desmond

    2014-10-10

    Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies. PMID:25302167

  5. Docetaxel as adjuvant and neoadjuvant treatment for patients with breast cancer.

    PubMed

    Heys, Steven D; Sarkar, Tarun; Hutcheon, Andrew W

    2004-10-01

    Developments in the role of adjuvant and neoadjuvant chemotherapy for the treatment of patients with breast cancer have focused on the taxes, in particular, docetaxel. This paper discusses the rationale for the introduction of docetaxel into the management of patients following surgery and also its role in those patients with locally-advanced disease, focussing on key clinical trials. The addition of docetaxel to standard adjuvant chemotherapeutic regimens does seem to result in an increased survival in some patients with early-stage disease. In the neoadjuvant setting, the addition of docetaxel to standard regimens does increase pathological response rates, which is a surrogate marker of eventual outcome. PMID:15461550

  6. Lagged Relationships Among Sleep Disturbance, Fatigue, and Depressed Mood During Chemotherapy

    PubMed Central

    Jim, Heather S.L.; Jacobsen, Paul B.; Phillips, Kristin M.; Wenham, Robert M.; Roberts, William; Small, Brent J.

    2013-01-01

    Objective Recent research suggests that sleep disturbance, fatigue, and depressed mood form a symptom cluster in patients treated with chemotherapy. To date, however, no studies have examined lagged relationships among these symptoms during chemotherapy, a time when symptom variability is high. The aim of the current study was to examine lagged changes among daily symptoms during platinum-based chemotherapy. Methods Participants were 78 women with gynecologic cancer (mean age 63, SD=11; 91% Caucasian; 97% non-Hispanic). Sleep disturbance was assessed via wrist actigraphy, while fatigue and depressed mood were assessed via daily diary in the week after participants’ first chemotherapy infusion. Latent change score models (LCS) were used to examine lagged relationships between symptom pairs. Results High levels of sleep disturbance (i.e., minutes awake at night) were associated with earlier subsequent peaks in fatigue, while high levels of fatigue were associated with higher subsequent levels of depressed mood. Conclusions These findings suggest that sleep disturbance, fatigue, and depressed mood occur in a cascade pattern during chemotherapy, in which increases in sleep disturbance contribute to fatigue, which in turn contributes to depressed mood. Interventions targeting symptoms early in the cascade, such as sleep disturbance, may provide benefits across multiple downstream symptoms. PMID:23437852

  7. RAGE Genetic Polymorphisms Are Associated with Risk, Chemotherapy Response and Prognosis in Patients with Advanced NSCLC

    PubMed Central

    Hua, Feng; Wang, Bin; Mao, Wei; Feng, Xueren

    2012-01-01

    Aim To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). Method This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, −429T/C, −374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. Results All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. Conclusion The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC. PMID:23071492

  8. [Chemotherapy of gastrointestinal tumors (review of the literature)].

    PubMed

    Mayr, A C

    1978-12-01

    There exist no common recommendations for palliative therapy of gastrointestinal cancer. Fluorouracil has been used for a long time, remission rates reported range from 0% to 80%. In larger series they figure about 20% but without prolongation of survival in responders. Although this drug is used for 20 years optimal dose and timing is still unknown. By combination of fluorouracil with other drugs remission rates were improved and in responders survival was prolonged (mitomycin C and/or adriamycin in gastric cancer, methyl-CCNU in colorectal cancer). The results of adjuvant chemotherapy of gastrointestinal cancer are contradictory, the routine usage is not recommendable. Adjuvant as well as palliative chemotherapy must be improved by controlled clinical trials. PMID:83561

  9. Classification of Laser Vaccine Adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Poznansky, Mark C

    2016-01-01

    An immunologic adjuvant, which enhances the magnitude and quality of immune responses to vaccine antigens, has become an essential part of modern vaccine practice. Chemicals and biologicals have been typically used for this purpose, but there are an increasing number of studies that are being conducted on the vaccine adjuvant effect of laser light on the skin. Currently, four different types or classes of laser devices have been shown to systemically enhance immune responses to intradermal vaccination: ultra-short pulsed lasers, non-pulsed lasers, non-ablative fractional lasers and ablative fractional lasers. Aside from involving the application of laser light to the skin in a manner that minimizes discomfort and damage, each type of laser vaccine adjuvant involves emission parameters, modes of action and immunologic adjuvant effects that are quite distinct from each other. This review provides a summary of the four major classes of “laser vaccine adjuvant” and clarifies and resolves their characteristics as immunologic adjuvants. These aspects of each adjuvant’s properties will ultimately help define which laser would be most efficacious in delivering a specific clinical benefit with a specific vaccine. PMID:27104047

  10. The role of adjuvant radiation in endometrial cancer.

    PubMed

    Diavolitsis, Virginia; Boyle, John; Singh, Diljeet K; Small, William

    2009-04-15

    Endometrial cancer treatment ideally begins with a staging procedure including abdominopelvic washing, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node evaluation. Recommendations for postoperative adjuvant radiotherapy are determined by recurrence risk. Patients who have undergone staging and have early stage I disease and an absence of high-risk features for recurrence generally are treated with surgery alone. Intermediate-risk patients--those with high-risk stage I disease and some stage II patients--may benefit from adjuvant radiation therapy. Several randomized trials show that radiation therapy improves locoregional control among intermediate-risk patients. The optimal type of radiation therapy, whether vaginal brachytherapy or whole-pelvic radiation therapy, remains undetermined, though treatment decision can be guided by risk factors not encompassed by the current staging system. Patients with high-risk stage II disease and stage III disease generally receive external-beam radiotherapy, often in combination with chemotherapy. Chemotherapy alone in advanced-stage patients is a consideration, given the results of the Gynecologic Oncology Group (GOG)-122 trial. PMID:19476264

  11. Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer

    PubMed Central

    Galaal, Khadra; Naik, Raj; Bristow, Robert E; Patel, Amit; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background Most women with advanced epithelial ovarian cancer will ultimately develop recurrent disease after completion of initial treatment with primary surgery and adjuvant chemotherapy. Secondary cytoreductive surgery may have survival benefits in selected patients. However, a number of chemotherapeutic agents are active in recurrent ovarian cancer and the standard treatment of patients with recurrent ovarian cancer remains poorly defined. Objectives To evaluate the effectiveness and safety of secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Register of Controlled Trials, (CENTRAL) Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. Selection criteria We searched for RCTs, quasi-randomised trials and non-randomised studies that compared secondary cytoreductive surgery and chemotherapy to chemotherapy alone in women with recurrent epithelial ovarian cancer. Data collection and analysis Three reviewers independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. Main results The search strategy identified 1431 unique references of which all were excluded on the basis of title and abstract. Authors’ conclusions We found no evidence from RCTs to inform decisions about secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Ideally, a large randomised controlled trial or, at the very least, well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare these treatment modalities. The results of the ongoing RCT AGO

  12. Chemokines as Cancer Vaccine Adjuvants

    PubMed Central

    Bobanga, Iuliana D.; Petrosiute, Agne; Huang, Alex Y.

    2013-01-01

    We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs) and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants. PMID:24967094

  13. Triple Negative Breast Cancer: Role of Specific Chemotherapy Agents

    PubMed Central

    Isakoff, Steven J.

    2010-01-01

    Cytotoxic chemotherapy remains the mainstay of treatment for triple negative breast cancer (TNBC) despite the promise of new targeted and biologic agents. Many studies have shown significant benefit of chemotherapy in the neoadjuvant, adjuvant and metastatic treatment of TNBC. Neoadjuvant chemotherapy studies have consistently reported higher response rates in TNBC than non-TNBC, and pathologic complete response has been shown to predict improved long term outcomes for TNBC. Although the specific adjuvant regimens that may be most effective for TNBC are still being determined, third generation chemotherapy regimens utilizing dose dense or metronomic polychemotherapy are among the most effective tools presently available. The role of specific chemotherapy agents in the treatment of TNBC remains incompletely defined and warrants careful review to ensure the most effective therapy is delivered while minimizing unnecessary toxicity. Platinum agents have seen renewed interest in TNBC based on a growing body of preclinical and clinical data suggesting encouraging activity. Taxanes and anthracyclines are active in TNBC and remain important agents, but have not shown specific benefit over non-TNBC. Capecitabine has limited reported data in TNBC, but some reports suggest differential activity in TNBC compared to hormone receptor positive breast cancer. TNBC is itself a heterogeneous group in which subgroups such as BRCA1 mutation carriers may have particular sensitivity to platinum agents and relatively less sensitivity to taxanes. Therefore, the identification of additional molecular biomarkers to predict response to specific chemotherapy is required to further improve treatment strategies with the current menu of chemotherapy options and future combinations with targeted therapies. PMID:20164691

  14. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  15. Spray drift mitigation with spray mix adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  16. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  17. QS-21: a potent vaccine adjuvant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

  18. Selecting a specific pre- or postoperative adjuvant therapy for individual patients with operable gastric cancer.

    PubMed

    Briasoulis, Evangelos; Liakakos, Theodore; Dova, Lefkothea; Fatouros, Michael; Tsekeris, Pericles; Roukos, Dimitrios H; Kappas, Angelos M

    2006-06-01

    Although the very high locoregional recurrence rates reported with limited D0/D1 surgery can be reduced with extended D2 gastrectomy for operable gastric cancer, overall relapse and survival rates remain poor and can only be improved with adequate perioperative adjuvant treatment. However, despite intensive research, no regimen has been established as standard. Meta-analyses have demonstrated a marginal survival benefit with adjuvant chemotherapy. Two recent large randomized trials for operable gastric cancer, the MAGIC trial and the INT-0116 trial, provide evidence that some patients may benefit from perioperative chemotherapy and chemoradiation, respectively. However, while both trials suggest an overall survival benefit with adjuvant treatment, they don't provide the harm-benefit ratio for specific subsets of patients wih different extent of surgery (D1 or D2) and tumor stage (early [T1,2]/advanced [T3,4]). This lack of evidence complicates current therapeutic adjuvant decisions. Estimating the risk of local and distant recurrence (high, moderate or low) after D1 or D2 surgery in various tumor stages and the expected harm-benefit ratio, the authors provide useful information for decisions on adjuvant chemotherapy with or withour radiotherapy in individual patients. Research on newer cytotoxic and targeted agents may improve treatment efficacy. Simultaneously, advances with microarray-based gene-expression profiling signatures may improve individualized treatment decisions. However, the validation and translation of these genomic classifiers as biomarkers into a completed 'bench-to-bedside' cycle for tailoring treatment to individuals is a major challenge and limits inflated expectations. PMID:16761937

  19. Adjuvant radiotherapy in the treatment of gall bladder carcinoma: What is the current evidence.

    PubMed

    Mallick, Supriya; Benson, Rony; Haresh, K P; Julka, P K; Rath, G K

    2016-03-01

    Gall bladder carcinoma (GBC) is considered the fifth most common one of the most aggressive gastro intestinal tract malignancies. Owing to their large incidence randomised controlled trials have hardly been conducted to look into their optimum treatment. Over the years surgical resection has been considered the only curative treatment of these tumors. However, the outcome still remains guarded. The predominant pattern of failure is loco-regional followed by systemic. Hence, local adjuvant radiation has been used by different institutes with concurrent and adjuvant chemotherapy. The large retrospective series with their limitations showed improved survival in patients with regional spread or tumors infiltrating the liver when treated with adjuvant radiotherapy. In the present era with modern radiation techniques and target delineation radiation may further improve upon the impact without adding to the toxicity profile. Hence, radiation in gall bladder cancer needs a relook to optimize treatment outcome of such aggressive disease. PMID:26265290

  20. Preliminary Experience with Locoregional Intraarterial Chemotherapy of Uterine Cervical or Endometrial Cancer Using the Peripheral Implantable Port System (PIPS{sup TM}): A Feasibility Study

    SciTech Connect

    Strecker, Ernst-Peter; Heber, Ralf; Boos, Irene; Goettmann, Dieter; Heinrich, Dirk

    2003-04-15

    The purpose of this study was to assess the suitability of a percutaneously implantable catheter port system (PIPS)for repeated intraarterial locoregional chemotherapy (ILC) for cervical and endometrial carcinoma. In 30 patients with advanced, recurrent, or high-risk cervical (n 23) or endometrial(n = 7) carcinoma, PIPS for ILC was implanted via a femoral access, the catheter localized in the infrarenal abdominal aorta. Chemotherapy was performed adjuvantly after surgery(n = 14) or neo-adjuvantly to enable surgery, or for palliation (n = 16). Port implantation, catheter placement, and repeated port puncture was uneventful in all patients.Complications included catheter dislocation (n = 1),catheter thrombosis (n = 2), subcutaneous infection(n = 1), port-bed skin atrophy (n = 1),requiring port explantation in 3 patients. At 2 years follow-up,complete remission was observed in 7/14 patients with adjuvant chemotherapy, partial remission in 3/14. Successful down-staging could be achieved in 4/8 patients with neo-adjuvant chemotherapy. The PIPS is suitable for repeated ILC which may be a valuable method for pre- and post-surgical therapy of advanced or high-risk cervical and endometrial cancer, for adjuvant chemotherapy as well as neo-adjuvantly for down-staging, or for palliation.

  1. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    PubMed

    Shi, Mingguang; He, Jianmin

    2016-04-22

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials. PMID:26864276

  2. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

    PubMed Central

    Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-01-01

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes. PMID:25999351

  3. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.

    PubMed

    Ayub, Tiyasha H; Keyver-Paik, Mignon-Denise; Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-06-30

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes. PMID:25999351

  4. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    SciTech Connect

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas; Chao, K. S. Clifford; Nori, Dattatreyudu; Wernicke, A. Gabriella

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  5. Adjuvant Therapy for Thymic Carcinoma – A Decade of Experience in a Taiwan National Teaching Hospital

    PubMed Central

    Tseng, Yen-Han; Lin, Yi-Hsuan; Tseng, Yen-Chiang; Lee, Yu-Chin; Wu, Yu-Chung; Hsu, Wen-Hu; Yen, Sang-Hue; Whang-Peng, Jacqueline; Chen, Yuh-Min

    2016-01-01

    Background Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma. Methods To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014. Results Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS) and overall survival (OS) were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003). Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11). Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029). Among 30 patients (with stage I- IV carcinoma) who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months) than 2 patients who received adjuvant chemotherapy (5.9 months) or 4 patients who received concurrent chemoradiotherapy (7.5 months) after surgery (p = 0.003). Conclusions Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection. PMID:26757052

  6. EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

    PubMed Central

    Milovancev, Aleksandar; Stojsic, Vladimir; Zaric, Bojan; Kovacevic, Tomi; Sarcev, Tatjana; Perin, Branislav; Zarogoulidis, Konstantinos; Tsirgogianni, Katerina; Freitag, Lutz; Darwiche, Kaid; Tsavlis, Drosos; Zissimopoulos, Athanasios; Stratakos, Grigoris; Zarogoulidis, Paul

    2015-01-01

    Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA–IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data. PMID:26508876

  7. The effect of postoperative radiotherapy on the feasibility of optimal dose adjuvant CMF chemotheraphy in stage II breast carcinoma

    SciTech Connect

    Sulkes, A.; Brufman, G.; Rizel, S.; Weshler, Z.; Biran, S.; Fuks, Z.

    1983-01-01

    The impact of a number of variables upon the effectiveness of adjuvant chemotherapy given to 87 patients with Stage II breast carcinoma was retrospectively analyzed. Adjuvant chemotherapy consisted of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Drugs were given in optimal doses (85% or more of the planned dose) to 17% of the patients; in intermediate doses (66 to 84% of the planned dose) to 50% of the patients; and in low doses (65% or less of the planned dose) to 33% of the patients. Myelosuppression was the main reason for giving intermediate or low doses. At a median follow-up of three years, 84% of all patients remain alive. Radiation therapy preceding chemotherapy was given to 70% of the patients, concomitant irradation and chemotherapy to 15%, and 13 patients (15%) received chemotheapy only. Of the 14 patients who received optimal doses of CMF, 12 (86%) also received radiation therapy. Disease-free survival at three years is similar for irradiated and nonirradiated patients, but the latter have a higher incidence of local recurrence (5% vs. 15%), although the difference is not statistically significant. Delay in the intiation of chemotherapy, mostly because of the administration of postoperative irradiation, adversely affected the probability and duration of disease-free survival, particulararly in premenopausal women in whom chemotherapy was started within more than 90 days of mastectomy. The administration of optimal doses of adjuvant chemotherapy should follow the primary treatment to the breast tumor as closely as possible. If radiation therapy is indicated as well, it should be delivered concomitantly with chemotherapy, given the feasibility of administering both modalities simultaneously, as demonstrated in this study.

  8. Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues….

    PubMed

    Leary, Alexandra; Cowan, Renee; Chi, Dennis; Kehoe, Sean; Nankivell, Matthew

    2016-01-01

    Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies. PMID:27249696

  9. Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer

    Cancer.gov

    Treatment with trastuzumab for 1 year following standard chemotherapy improved disease-free survival in women with HER2-positive early breast cancer, according to 4-year follow-up results of the Herceptin Adjuvant (HERA) trial reported February 25, 2011,

  10. Chemotherapy in Prostate Cancer.

    PubMed

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  11. The association of adjuvant therapy with survival at the population level following pancreatic adenocarcinoma resection

    PubMed Central

    Kagedan, Daniel J.; Raju, Ravish S.; Dixon, Matthew E.; Shin, Elizabeth; Li, Qing; Liu, Ning; Elmi, Maryam; El-Sedfy, Abraham; Paszat, Lawrence; Kiss, Alexander; Earle, Craig C.; Mittmann, Nicole; Coburn, Natalie G.

    2016-01-01

    Background Using a retrospective observational cohort approach, the overall survival (OS) following curative-intent resection of pancreatic adenocarcinoma (PC) was defined at the population level according to adjuvant treatment, and predictors of OS were identified. Methods Patients undergoing resection of PC in the province of Ontario between 2005 and 2010 were identified using the provincial cancer registry, and linked to databases that include all treatments received and outcomes experienced in the province. Pathology reports were abstracted for staging and margin status. Patients were identified as having received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant treatment (NAT). Kaplan–Meier survival analysis of patients surviving ≥6 months was performed, and predictors of OS identified by log-rank test. Cox multivariable analysis was used to define independent predictors of OS. Results Among the 473 patients undergoing PC resection, the median survival was 17.8 months; for the 397 who survived ≥6 months following surgery, the 5-year OS for the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584). Lymph node-negative patients demonstrated improved OS associated with chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25–3.83 for NAT vs. CT). Conclusions Following PC resection, only patients with negative lymph nodes demonstrated improved OS associated with adjuvant chemotherapy. PMID:27037203

  12. Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.

    PubMed

    Vacchelli, Erika; Ma, Yuting; Baracco, Elisa E; Sistigu, Antonella; Enot, David P; Pietrocola, Federico; Yang, Heng; Adjemian, Sandy; Chaba, Kariman; Semeraro, Michaela; Signore, Michele; De Ninno, Adele; Lucarini, Valeria; Peschiaroli, Francesca; Businaro, Luca; Gerardino, Annamaria; Manic, Gwenola; Ulas, Thomas; Günther, Patrick; Schultze, Joachim L; Kepp, Oliver; Stoll, Gautier; Lefebvre, Céline; Mulot, Claire; Castoldi, Francesca; Rusakiewicz, Sylvie; Ladoire, Sylvain; Apetoh, Lionel; Bravo-San Pedro, José Manuel; Lucattelli, Monica; Delarasse, Cécile; Boige, Valérie; Ducreux, Michel; Delaloge, Suzette; Borg, Christophe; André, Fabrice; Schiavoni, Giovanna; Vitale, Ilio; Laurent-Puig, Pierre; Mattei, Fabrizio; Zitvogel, Laurence; Kroemer, Guido

    2015-11-20

    Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses. PMID:26516201

  13. Vaccine adjuvants as potential cancer immunotherapeutics.

    PubMed

    Temizoz, Burcu; Kuroda, Etsushi; Ishii, Ken J

    2016-07-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund's adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  14. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  15. Vaccine adjuvants as potential cancer immunotherapeutics

    PubMed Central

    Temizoz, Burcu; Kuroda, Etsushi

    2016-01-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  16. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report

    PubMed Central

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    Patient: Male, 71 Final Diagnosis: Neuroendocrine cancer bladder Symptoms: Dysuria • haematuria Medication: — Clinical Procedure: Transurethral resection of the bladder tumor Specialty: Oncology Objective: Rare disease Background: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer. Case Report: A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free. Conclusions: A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder. PMID:27072610

  17. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report.

    PubMed

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    BACKGROUND Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer. CASE REPORT A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free. CONCLUSIONS A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder. PMID:27072610

  18. Chemotherapy in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Gyawali, Bishal; Shimokata, Tomoya; Honda, Kazunori; Ando, Yuichi

    2016-03-01

    Chemotherapy, in combination with a local treatment, has a role in nearly all the settings of locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment: as definitive, adjuvant or induction therapy. However, despite many years of trials, controversies still exist regarding the best approach to using chemotherapy in the multi-modal treatment of LAHNSCC. Opinions are divided on sequential versus concurrent use of chemotherapy and radiotherapy for unresectable LAHNSCC. More debate exists on whether the addition of induction chemotherapy to concomitant chemoradiotherapy is clinically meaningful. After the approval of cetuximab in combination with radiotherapy for this disease, making treatment choices have become further complicated. Although new data from trials are arriving every year, the results have been inconclusive. In this review, we provide the readers with the latest information on various strategies of using chemotherapy and cetuximab that will help to make an evidence-based decision in the treatment of LAHNSCC, including the approach to larynx preservation. We conclude that with the available information, concurrent chemoradiotherapy should be preferred over induction chemotherapy, except in the setting of larynx preservation. Furthermore, given the paucity of positive data and severe financial toxicity associated with cetuximab, concurrent chemoradiotherapy should be the preferred choice over cetuximab-radiotherapy. Future trials in head and neck cancer should be properly planned to address these controversies and provide clear solutions. PMID:26924194

  19. High Id1 expression, a generally negative prognostic factor, paradoxically predicts a favorable prognosis for adjuvant paclitaxel plus cisplatin therapy in surgically treated lung cancer patients

    PubMed Central

    Cheng, Yu-Jen; Lee, Yi-Chen; Chiu, Wen-Chin; Tsai, Jen-Wei; Su, Yu-Han; Hung, Amos C.; Chang, Po-Chih; Huang, Chih-Jen; Chai, Chee-Yin; Yuan, Shyng-Shiou F.

    2014-01-01

    Adjuvant chemotherapy is commonly given to surgically treated non-small-cell lung cancer (NSCLC) patients. However, the prerequisite for chemotherapy needs to be scrutinized in order to maximize the benefits to patients. In this study, we observed that NSCLC cells with high Id1 protein expression were vulnerable to the treatment of paclitaxel and cisplatin. In addition, paclitaxel and cisplatin caused Id1 protein degradation through ubiquitination. In the nude mice xenograft model, the tumor growth was reduced to a large degree in the Id1-overexpressing group upon treatment with paclitaxel and cisplatin. Furthermore, immunohistochemical staining for Id1 followed by Kaplan-Meier survival analysis showed that surgically treated NSCLC patients with high Id1 expression in primary tumor tissues had better disease-free and overall survivals after adjuvant paclitaxel and cisplatin chemotherapy. In summary, our current data suggest that Id1, a generally negative prognostic factor, predicts a favorable prognosis in the case of surgically treated NSCLC patients receiving the definitive adjuvant chemotherapy. The distinct role of Id1 reported in this study may arise from the phenomenon of Id1 dependence of NSCLC cells for survival, which renders the cancer cells additionally susceptive to the adjuvant chemotherapy with paclitaxel and cisplatin. PMID:25344919

  20. Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study

    PubMed Central

    Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.

    2013-01-01

    Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

  1. Chemotherapy-Related Neurotoxicity.

    PubMed

    Taillibert, Sophie; Le Rhun, Emilie; Chamberlain, Marc C

    2016-09-01

    Chemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer. PMID:27443648

  2. Biosafe Nanoscale Pharmaceutical Adjuvant Materials

    PubMed Central

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

    2014-01-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

  3. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

  4. Polysaccharides: Candidates of promising vaccine adjuvants.

    PubMed

    Li, Pingli; Wang, Fengshan

    2015-04-01

    Aluminium-based adjuvants remain the only adjuvants approved for human use in the USA for over 80 years because of alum's simplicity, tolerability, safety and cost-efficiency. Recent development of vaccines, especially the increasing applications of recombinant subunit and synthetic vaccines, makes aluminium adjuvants cannot stimulate enough immunity to the antigens, since aluminium adjuvants can only induce Th2 type immune responses. So, novel adjuvants are urgent to make up the disadvantages of aluminium adjuvants. However, some major hurdles need to be overcome, not only the scientific knowledge of adjuvants but also unacceptable side-effects and toxicity. A number of carbohydrate-based polysaccharides from plant, bacterial, yeast and synthetic sources can act as pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition receptors (PRRs) on immune cells, followed by triggering innate immunity and regulating adaptive immunity. What is more, polysaccharides are safe and biodegradable without tissue deposits as observed in aluminium adjuvants. Therefore, polysaccharide-based compounds and formulations are potential vaccine adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants investigated in recent years. PMID:25994059

  5. Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

    SciTech Connect

    Krishnan, Sunil Rana, Vishal; Evans, Douglas B.; Varadhachary, Gauri; Das, Prajnan; Bhatia, Sumita; Delclos, Marc E.; Janjan, Nora A.; Wolff, Robert A.; Crane, Christopher H.; Pisters, Peter W.

    2008-03-01

    Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

  6. Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma.

    PubMed

    Kemeny, N; Fata, F

    1999-01-01

    Hepatic metastases from colorectal carcinoma are common and may be resected for cure. The response of liver metastases to systemic chemotherapy is low. In contrast, hepatic arterial chemotherapy produces higher response rates than systemic chemotherapy, but randomized trials have not definitely proved a survival advantage because they allowed cross over. Most adjuvant portal vein chemotherapy studies have shown a survival advantage over the control group, but it is not clear whether this benefit is from the portal vein therapy or from immediate postoperative chemotherapy, since there is rarely a reduction in liver metastases. We describe the results of systemic, hepatic artery infusion, and portal therapy for patients with liver metastases of colorectal carcinoma. PMID:10436236

  7. Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience

    PubMed Central

    Wolff, Antonio C.; Blackford, Amanda L.; Visvanathan, Kala; Rugo, Hope S.; Moy, Beverly; Goldstein, Lori J.; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S.; Theriault, Richard L.; Hughes, Melissa E.; Weeks, Jane C.; Karp, Judith E.

    2015-01-01

    Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. PMID

  8. Adjuvant progestagens for endometrial cancer

    PubMed Central

    Martin-Hirsch, Pierre PL; Bryant, Andrew; Keep, Sarah L; Kitchener, Henry C; Lilford, Richard

    2014-01-01

    Background Endometrial cancer is the most common genital tract carcinoma among women in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. Objectives To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009. Selection criteria Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses.. Main results Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27). Authors’ conclusions There

  9. Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer

    PubMed Central

    Stefanou, Dimitra T.; Bamias, Aristotelis; Episkopou, Hara; Kyrtopoulos, Soterios A.; Likka, Maria; Kalampokas, Theodore; Photiou, Stylianos; Gavalas, Nikos; Sfikakis, Petros P.; Dimopoulos, Meletios A.; Souliotis, Vassilis L.

    2015-01-01

    Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that

  10. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

    PubMed Central

    2011-01-01

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561

  11. Thermal potentiation of chemotherapy by magnetic nanoparticles

    PubMed Central

    Torres-Lugo, Madeline; Rinaldi, Carlos

    2014-01-01

    Clinical studies have demonstrated the effectiveness of hyperthermia as an adjuvant for chemotherapy and radiotherapy. However, significant clinical challenges have been encountered, such as a broader spectrum of toxicity, lack of patient tolerance, temperature control and significant invasiveness. Hyperthermia induced by magnetic nanoparticles in high-frequency oscillating magnetic fields, commonly termed magnetic fluid hyperthermia, is a promising form of heat delivery in which thermal energy is supplied at the nanoscale to the tumor. This review discusses the mechanisms of heat dissipation of iron oxide-based magnetic nanoparticles, current methods and challenges to deliver heat in the clinic, and the current work related to the use of magnetic nanoparticles for the thermal-chemopotentiation of therapeutic drugs. PMID:24074390

  12. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved. PMID:12756087

  13. Adjuvant systemic therapy in older women with breast cancer

    PubMed Central

    Leone, Julieta; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents. PMID:27524919

  14. Surgeons’ Volume of Colorectal Cancer Procedures and Collaborative Decision-making about Adjuvant Therapies

    PubMed Central

    Rogers, Selwyn O.; Ayanian, John Z.; Ko, Clifford Y.; Kahn, Katherine L.; Zaslavsky, Alan M.; Sandler, Robert S.; Keating, Nancy L.

    2011-01-01

    Background Few studies have assessed associations of surgeons’ practice volume with processes of care that lead to better outcomes. Objective We surveyed surgeons treating colorectal cancer to determine whether high-volume surgeons were more likely to collaborate with other physicians in decisions about adjuvant therapies. Subjects and methods Surgeons caring for patients with colorectal cancer in multiple regions and health-care organizations were surveyed to assess their volume of colorectal cancer resections and participation in decisions about adjuvant chemotherapy and radiation therapy. We used logistic regression to assess physician and practice characteristics associated with surgical volume and the relation of surgical volume and these other characteristics to collaborative decision-making regarding adjuvant therapies. Results Of 635 responding surgeons, those who identified themselves as surgical oncologists or colorectal surgeons were more likely than others to report high volume of colorectal cancer resections (p<.001), as were those who practiced at a comprehensive cancer center (P=.06) and attended tumor board meetings weekly (vs. quarterly or less, P=.09). Most surgeons reported a collaborative role in decisions about chemotherapy and radiation therapy. However, in adjusted analyses, higher-volume surgeons more often reported a collaborative role with other physicians in decisions about chemotherapy (P<0.001) and radiation therapy (P<0.001). Conclusions Higher-volume surgeons are more likely to report collaborating with other physicians in decisions about adjuvant therapies for patients following colorectal cancer surgery. This collaborative decision-making of higher-volume surgeons may contribute to outcome differences by surgeon volume. PMID:19855265

  15. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    PubMed Central

    Chen, Jianhua; Wu, Shengqi; Hu, Chenping; Yang, Yicheng; Rajan, Narayan; Chen, Yun; Yang, Canjuan; Li, Jianfeng; Chen, Wendong

    2016-01-01

    Objective The objective of this study was to compare hospital costs per treatment cycle (HCTC) for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC) in Chinese patients. Methods Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs), paclitaxel–platinum (39 pairs), gemcitabine–platinum (93 pairs), and vinorelbine–platinum (73 pairs), respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient −0.174, P=0.015), which included patients experiencing any hematological adverse events (coefficient −0.199, P=0.013), neutropenia (coefficient −0.426, P=0.021), or leukopenia (coefficient −0.406, P=0.001), pemetrexed–platinum had the highest total HCTC (median difference from RMB 1,692 to RMB 7,400, P<0.001) among platinum-based doublets because of its higher drug acquisition costs (median difference from RMB 4,636 to RMB 7,332, P<0.001). Conclusion Among Chinese patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC, the higher acquisition costs for nonplatinum cytotoxic drugs associated with pemetrexed–platinum could be partially offset by its significantly lower hospital

  16. TUMOR AND HOST FACTORS THAT MAY LIMIT EFFICACY OF CHEMOTHERAPY IN NON-SMALL CELL AND SMALL CELL LUNG CANCER

    PubMed Central

    Stewart, David J.

    2010-01-01

    While chemotherapy provides useful palliation, advanced lung cancer remains incurable since those tumors that are initially sensitive to therapy rapidly develop acquired resistance. Resistance may arise from impaired drug delivery, extracellular factors, decreased drug uptake into tumor cells, increased drug efflux, drug inactivation by detoxifying factors, decreased drug activation or binding to target, altered target, increased damage repair, tolerance of damage, decreased proapoptotic factors, increased antiapoptotic factors, or altered cell cycling or transcription factors. Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the strongest clinical evidence is for taxane resistance with elevated expression or mutation of class III β-tubulin (and possibly α tubulin), platinum resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1 expression, and resistance to several agents and COX-2 expression (although COX-2 inhibitors have had minimal impact on drug efficacy clinically). Tumors expressing high BRCA1 may have increased resistance to platinums but increased sensitivity to taxanes. Limited early clinical data suggest that chemotherapy resistance in NSCLC may also be increased with decreased expression of cyclin B1 or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH, survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R inhibitors may increase efficacy of chemotherapy, particularly in squamous cell carcinomas. Equivocal data (with some positive studies but other negative studies) suggest that NSCLC tumors with some EGFR mutations may have increased sensitivity to chemotherapy, while K-ras mutations and

  17. Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer.

    PubMed

    Stewart, David J

    2010-09-01

    While chemotherapy provides useful palliation, advanced lung cancer remains incurable since those tumors that are initially sensitive to therapy rapidly develop acquired resistance. Resistance may arise from impaired drug delivery, extracellular factors, decreased drug uptake into tumor cells, increased drug efflux, drug inactivation by detoxifying factors, decreased drug activation or binding to target, altered target, increased damage repair, tolerance of damage, decreased proapoptotic factors, increased antiapoptotic factors, or altered cell cycling or transcription factors. Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the strongest clinical evidence is for taxane resistance with elevated expression or mutation of class III beta-tubulin (and possibly alpha tubulin), platinum resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1 expression, and resistance to several agents and COX-2 expression (although COX-2 inhibitors have had minimal impact on drug efficacy clinically). Tumors expressing high BRCA1 may have increased resistance to platinums but increased sensitivity to taxanes. Limited early clinical data suggest that chemotherapy resistance in NSCLC may also be increased with decreased expression of cyclin B1 or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH, survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R inhibitors may increase efficacy of chemotherapy, particularly in squamous cell carcinomas. Equivocal data (with some positive studies but other negative studies) suggest that NSCLC tumors with some EGFR mutations may have increased sensitivity to chemotherapy, while K-ras mutations

  18. Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.

    2005-08-01

    Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

  19. [Standards and new developments in the chemotherapy of glioblastomas].

    PubMed

    Weller, M

    2005-10-01

    For 25 years involved-field radiotherapy has remained the mainstay of postoperative treatment for glioblastoma. In contrast, the role of adjuvant chemotherapy in addition to radiotherapy has remained controversial. A recent randomized multinational phase III trial (EORTC 26 981/22 981/NCIC CE.3) assessing concomitant and adjuvant chemotherapy with the alkylating agent, temozolomide, in addition to radiotherapy in newly diagnosed glioblastoma defines an increase in median survival from 12.1 months with radiotherapy alone to 14.6 months with radiochemotherapy and an increase in the 2-year survival rate from 10 to 26 %. Subgroup analysis revealed that the gain in survival in the experimental arm was largely achieved in patients with glioblastomas which exhibited a methylation of the promoter region of the O (6)-methylguanine DNA methyltransferase (MGMT) gene and thus did not express MGMT. MGMT is a DNA repair enzyme which repairs DNA lesions induced by chemotherapy with alkylating agents. The cellular MGMT stores are consumed during DNA repair, suggesting that temozolomide itself may deplete MGMT and thus overcome its own most important pathway of resistance. EORTC 26 981/22 981/NCIC CE.3 thus defines a milestone in the treatment of glioblastoma and will provide a platform for further efforts at improving the outcome for patients suffering from this still invariably fatal neoplasm. PMID:16208603

  20. Selection of chemotherapy for non-small cell lung cancer is facilitated by new therapeutic strategies

    PubMed Central

    Wang, Zhehai

    2014-01-01

    Nowadays, advanced non-small cell lung cancer is still an incurable disease. Recent researches have led to considerable progress in the treatment of non-small cell lung cancer. This article reviews the main studies on chemotherapy on non-small cell lung cancer and discusses the new therapeutic strategies available to date. Stable disease (SD) is necessary in chemotherapy for tumor. The proportion of population with responders or SD basically maintained similar regardless of regimens. The overall survival after chemotherapy for patients with SD was lower than patients with responders, and higher than patients with progressive disease. Greater benefits could be achieved in patients with effective induction chemotherapy using chemotherapeutic agents for maintenance therapy, whereas the benefits were relatively small for patients with SD. It has been found that epidermal growth factor receptor (EGFR) mutation status had certain correlation with the efficacy of chemotherapy. First-line chemotherapy has shown advantages in effective rate and progression free survival on EGFR mutant. EGFR mutation produced significant effects on the efficacy of postoperative adjuvant chemotherapy. Patients with EGFR mutation had a higher effective rate than wild-type EGFR patients, and patients with responders had a greater benefit in progression free survival from maintenance therapy. However, it is still necessary to carry out more careful and deeper studies and analyses on traditional cytotoxic chemotherapy, to further optimize cytotoxic chemotherapy and to use molecular targeted agents with different mechanisms. PMID:25550891

  1. Chemotherapy (For Parents)

    MedlinePlus

    ... sample before beginning chemotherapy to evaluate kidney function. Giving your child plenty of fluids to drink will ... eating, after using the bathroom, and after touching animals. They shouldn't share cups or utensils with ...

  2. Recruitment of trimeric proliferating cell nuclear antigen by G1-phase cyclin-dependent kinases following DNA damage with platinum-based antitumour agents

    PubMed Central

    He, G; Kuang, J; Koomen, J; Kobayashi, R; Khokhar, A R; Siddik, Z H

    2013-01-01

    Background: In cycling tumour cells, the binary cyclin-dependent kinase Cdk4/cyclin D or Cdk2/cyclin E complex is inhibited by p21 following DNA damage to induce G1 cell-cycle arrest. However, it is not known whether other proteins are also recruited within Cdk complexes, or their role, and this was investigated. Methods: Ovarian A2780 tumour cells were exposed to the platinum-based antitumour agent 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinum(IV) (DAP), which preferentially induces G1 arrest in a p21-dependent manner. The Cdk complexes were analysed by gel filtration chromatography, immunoblot and mass spectrometry. Results: The active forms of Cdk4 and Cdk2 complexes in control tumour cells have a molecular size of ∼140 kDa, which increased to ∼290 kDa when inhibited following G1 checkpoint activation by DAP. Proteomic analysis identified Cdk, cyclin, p21 and proliferating cell nuclear antigen (PCNA) in the inhibited complex, and biochemical studies provided unequivocal evidence that the increase in ∼150 kDa of the inhibited complex is consistent with p21-dependent recruitment of PCNA as a trimer, likely bound to three molecules of p21. Although p21 alone was sufficient to inhibit the Cdk complex, PCNA was critical for stabilising p21. Conclusion: G1 Cdk complexes inhibited by p21 also recruit PCNA, which inhibits degradation and, thereby, prolongs activity of p21 within the complex. PMID:24104967

  3. Quantitative imaging of platinum based on laser ablation-inductively coupled plasma-mass spectrometry to investigate toxic side effects of cisplatin