[A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

PubMed

Takase, Koki; Murata, Kohei; Kagawa, Yoshinori; Nose, Yohei; Kawai, Kenji; Sakamoto, Takuya; Naito, Atsushi; Murakami, Kohei; Katsura, Yoshiteru; Omura, Yoshiaki; Takeno, Atsushi; Nakatsuka, Shinichi; Takeda, Yutaka; Kato, Takeshi; Tamura, Shigeyuki

2018-01-01

Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

Treatment using oxaliplatin and S-1 adjuvant chemotherapy for pathological stage III gastric cancer: a multicenter phase II study (TOSA trial) protocol.

PubMed

Namikawa, Tsutomu; Maeda, Hiromichi; Kitagawa, Hiroyuki; Oba, Koji; Tsuji, Akihito; Yoshikawa, Takaki; Kobayashi, Michiya; Hanazaki, Kazuhiro

2018-02-13

Recent studies demonstrated the efficacy of S-1-based adjuvant chemotherapy administered for six months after curative surgery for stage III gastric cancer; however, it is unproven whether this type of combination chemotherapy is more effective than the standard adjuvant chemotherapy of S-1 for one year. This multicenter phase II study evaluate the efficacy and safety of adjuvant chemotherapy using S-1 plus oxaliplatin followed by S-1 for up to one year for curatively resected stage III gastric cancer in patients aged over 20 years. Treatment initially comprises oral fluoropyrimidine S-1 (80 mg/m 2 ) administered twice daily for the first 2 weeks of a 3-week cycle. On day 1 of a second 3-week cycle, patients will receive 100 mg/m 2 of intravenous oxaliplatin followed by 80 mg/m 2 of S-1 (maximum 8 cycles). Then, the patients will receive 80 mg/m 2 of S-1 daily for 4 weeks, followed by 2 weeks of no chemotherapy. This 6-week cycle will be repeated during the first year after surgery. The primary endpoint is relapse-free survival for 3 years and secondary endpoints are safety, including the incidence of adverse events, and grading of neuropathy with each treatment cycle. The planned sample size of 75 patients is appropriate for this trial. The data will be analyzed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance. In contrast to previous trials, the current study involves administration of S-1 until one year after surgery in addition to prior S-1 plus oxaliplatin, and is the first study to evaluate the safety and efficacy of S-1 plus oxaliplatin followed by S-1 for up to one year in patients with curatively resected stage III gastric cancer. This trial is registered in the University Hospital Medical Information Network's Clinical Trials Registry (UMIN-CTR) registration number, R000029656  ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029656 ). Registered January 24, 2017.

Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects.

PubMed

Vyas, Purvi; Thakar, A B; Baghel, M S; Sisodia, Arvind; Deole, Yogesh

2010-10-01

Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy.

Adjuvant chemotherapy for osteosarcoma.

PubMed

Eilber, F R; Rosen, G

1989-08-01

present to minimally include high-dose methotrexate, Adriamycin, and cisplatin. It would also appear from several of these reports that not only is the adjuvant use of these chemotherapeutic agents indicated, but that the preoperative use of these agents has had significant advantages. The neoadjuvant chemotherapy begins the essential systemic chemotherapy at a very early stage, allows histologic assessment of treatment effect, permits altering drug regimens postoperative, and in many reported trials has allowed less than amputative surgery (limb salvage) to be performed. Finally, close follow-up of patients with osteosarcoma has therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)

Efficacy of adjuvant chemotherapy after surgery when considered over all cancer types: a synthesis of meta-analyses.

PubMed

Bowater, Russell J; Abdelmalik, Sally M E; Lilford, Richard J

2012-10-01

Despite a large number of clinical trials having been conducted to assess the efficacy of adjuvant chemotherapy after surgery for various cancers, whether it is best to use this treatment remains a generally contentious issue for many common cancers. The purpose of this study was to ascertain whether any general conclusions can be drawn about the efficacy or inefficacy of this treatment within different cancer classifications. Meta-analyses of randomized, controlled trials (RCTs) of adjuvant chemotherapy after surgery were synthesized over as many types of cancer as possible. Data sources were Medline, Embase, and the Cochrane library. Eligible meta-analyses were meta-analyses of RCTs for any type of cancer that compared surgery followed by adjuvant chemotherapy with surgery followed by no adjuvant chemotherapy. The literature search found 25 meta-analyses for 15 cancer types that satisfied the criteria necessary for detailed analysis within this study. The estimates of relative risk for all cause mortality were reported as being less than one (indicating adjuvant chemotherapy is beneficial) by all meta-analyses apart from a meta-analysis for colorectal cancer metastasized to the liver. Moreover, 15 of these meta-analyses also reported that the 95% confidence interval for this relative risk is less than one (indicating statistical significance at the 5% level). The results for all cancer types included in this study except for cancer metastasized to the liver can be thought of as supporting each other through the idea of there being a common treatment effect or at least a common range of effect across all (or most) of these cancer types. For example, with regard to cancer types where the evidence in favor of adjuvant chemotherapy after surgery is only moderately strong, the results of this study may encourage more clinicians to regard the use of this treatment as standard practice.

Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma

PubMed Central

Galaal, Khadra; Godfrey, Keith; Naik, Raj; Kucukmetin, Ali; Bryant, Andrew

2014-01-01

Background Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of patients with advanced uterine carcinosarcoma is poor with pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. Objectives To evaluate the effectiveness and safety of radiotherapy and/or systemic chemotherapy in the management of stage III-IV persistent or recurrent uterine carcinosarcoma. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, The Cochrane Library 2010, Issue 2, MEDLINE and EMBASE to May 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. Data collection and analysis We independently abstracted data and assessed risk of bias. We pooled hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy in meta-analyses. Main results Three trials (579 women, of whom all were assessed at the end of the trials) met the inclusion criteria. Two trials (373 women with stage III-IV persistent or recurrent disease) found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide. There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, which affected significantly more women in the combination therapy group than in the ifosamide group. One trial found no statistically significant difference in the risk of death and disease progression in women who received whole abdominal irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95

Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.

PubMed

Neoptolemos, John P; Moore, Malcolm J; Cox, Trevor F; Valle, Juan W; Palmer, Daniel H; McDonald, Alexander C; Carter, Ross; Tebbutt, Niall C; Dervenis, Christos; Smith, David; Glimelius, Bengt; Charnley, Richard M; Lacaine, François; Scarfe, Andrew G; Middleton, Mark R; Anthoney, Alan; Ghaneh, Paula; Halloran, Christopher M; Lerch, Markus M; Oláh, Attila; Rawcliffe, Charlotte L; Verbeke, Caroline S; Campbell, Fiona; Büchler, Markus W

2012-07-11

Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

PubMed

Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

2018-05-22

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Does biomarker information impact breast cancer patients' preferences and physician recommendation for adjuvant chemotherapy?

PubMed

Partridge, Ann H; Sepucha, Karen; O'Neill, Anne; Miller, Kathy D; Baker, Emily; Dang, Chau T; Northfelt, Donald W; Sledge, George W; Schneider, Bryan P

2017-10-01

This study aimed to examine how biomarker information would impact patients' preferences and physicians' recommendations for adjuvant breast cancer therapy. At the 18-month follow-up, participants in a large, double-blind randomized controlled trial of adjuvant chemotherapy with bevacizumab or placebo (E5103) were surveyed about their preferred treatment (either chemotherapy A alone or chemotherapy A+B) in two hypothetical scenarios: (1) without biomarker information; and (2) after learning that they tested positive for a "B-receptor" which modestly increased both the benefit and toxicity expected with chemotherapy A+B. We performed a cross-sectional analysis of the prospectively collected survey data and used the McNemar's test to examine changes in treatment preferences. A one-time survey of clinical investigators who enrolled patients on the trial evaluated physician recommendations in response to the same biomarker information. 439 patients completed both scenarios on 18-month survey. Most participants preferred A+B in both scenario 1 and 2 (77 and 76% respectively). The increase in benefit and toxicity associated with the positive biomarker information in scenario 2 led 60/439 (14%) of patients to switch their treatment preference. The corresponding physician survey revealed that most physicians chose regimen A+B in scenario 1 (77%), and moreso after the biomarker information was available in scenario 2 (84%). Information about a positive biomarker indicating increased benefit and toxicity from additional chemotherapy did not change many participants' preferred treatment. The majority preferred the most effective course in both scenarios. Similarly, most investigators discounted increased toxicity and valued increased benefit. Parent Trial Registration: NCT00433511.

Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

PubMed Central

Sugarbaker, Paul H.; Bijelic, Lana

2012-01-01

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement. PMID:22888340

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

PubMed

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

2016-07-01

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. 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. 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. 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. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial

PubMed Central

Smyth, Elizabeth C.; Fassan, Matteo; Cunningham, David; Allum, William H.; Okines, Alicia F.C.; Lampis, Andrea; Hahne, Jens C.; Rugge, Massimo; Peckitt, Clare; Nankivell, Matthew; Langley, Ruth; Ghidini, Michele; Braconi, Chiara; Wotherspoon, Andrew; Grabsch, Heike I.

2016-01-01

Purpose The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate. PMID:27298411

Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

PubMed

Aebi, Stefan; Gelber, Shari; Anderson, Stewart J; Láng, István; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P; Geyer, Charles E; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L

2014-02-01

Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy

PubMed Central

Jang, Hoon; Hong, Kwonho; Choi, Youngsok

2017-01-01

Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients. PMID:28590419

What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

PubMed

Altorki, Nasser; Harrison, Sebron

2017-03-01

The majority of patients with operable esophageal cancers present with locally advanced disease, for which surgical resection as a sole treatment modality has been historically associated with poor survival. Even following radical resection, most of these patients will eventually succumb to their disease due to distant metastasis. For this reason, there has been intense interest in the role of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either chemotherapy, radiation therapy, or a combination of the two. Multiple studies of variable scope, design, and patient characteristics have been conducted to determine whether neoadjuvant therapy is warranted, and-if so-what is the best modality of treatment. Despite nearly three decades of study, decisions regarding neoadjuvant therapy for esophageal cancer remain controversial. Regardless, the available evidence provided by large, prospective studies supports preoperative chemotherapy as opposed to surgery alone. Therefore, in our opinion, there is no longer any question as to whether induction therapy is appropriate for locally advanced esophageal cancer. Less clear, however, is the evidence that the addition of radiation to chemotherapy in the preoperative setting is superior to neoadjuvant chemotherapy alone. Our group generally advocates for neoadjuvant chemotherapy alone followed by radical esophageal resection. The data for adjuvant therapy are soft, and particularly troubling is the high rate of treatment drop out in trials studying adjuvant therapy. Therefore, we strongly prefer neoadjuvant chemotherapy and reserve adjuvant chemotherapy for those rare, highly selected patients-patients with T1 tumors, for example-who do not receive neoadjuvant treatment and are found to have occult nodal disease at the time of surgery.

Association Between Adjuvant Chemotherapy and Overall Survival in Patients With Rectal Cancer and Pathological Complete Response After Neoadjuvant Chemotherapy and Resection.

PubMed

Dossa, Fahima; Acuna, Sergio A; Rickles, Aaron S; Berho, Mariana; Wexner, Steven D; Quereshy, Fayez A; Baxter, Nancy N; Chadi, Sami A

2018-04-19

Although American guidelines recommend use of adjuvant chemotherapy in patients with locally advanced rectal cancer, individuals who achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy are less likely to receive adjuvant treatment than incomplete responders. The association and resection of adjuvant chemotherapy with survival in patients with pCR is unclear. To determine whether patients with locally advanced rectal cancer who achieve pCR after neoadjuvant chemoradiation therapy and resection benefit from the administration of adjuvant chemotherapy. This retrospective propensity score-matched cohort study identified patients with locally advanced rectal cancer from the National Cancer Database from 2006 through 2012. We selected patients with nonmetastatic invasive rectal cancer who achieved pCR after neoadjuvant chemoradiation therapy and resection. We matched patients who received adjuvant chemotherapy to patients who did not receive adjuvant treatment in a 1:1 ratio. We separately matched subgroups of patients with node-positive disease before treatment and node-negative disease before treatment to investigate for effect modification by pretreatment nodal status. We compared overall survival between groups using Kaplan-Meier survival methods and Cox proportional hazards models. We identified 2455 patients (mean age, 59.5 years; 59.8% men) with rectal cancer with pCR after neoadjuvant chemoradiation therapy and resection. We matched 667 patients with pCR who received adjuvant chemotherapy and at least 8 weeks of follow-up after surgery to patients with pCR who did not receive adjuvant treatment. Over a median follow-up of 3.1 years (interquartile range, 1.94-4.40 years), patients treated with adjuvant chemotherapy demonstrated better overall survival than those who did not receive adjuvant treatment (hazard ratio, 0.44; 95% CI, 0.28-0.70). When stratified by pretreatment nodal status, only those patients with pretreatment node

Current status of adjuvant chemotherapy after radical cystectomy for deeply invasive bladder cancer.

PubMed

Skinner, D G; Daniels, J R; Lieskovsky, G

1984-07-01

Between March, 1976, and December, 1982, 70 of 157 patients (45%) undergoing single-stage radical cystectomy with pelvic lymphadenectomy and urinary diversion with the intent to cure invasive bladder cancer were found to have pathologic Stage P3B, P4 and/or N + disease. Thirty-four of the 70 patients received adjuvant prophylactic chemotherapy after cystectomy and 36 patients were followed expectantly. From 1976 through 1977 adjuvant chemotherapy consisted of cyclophosphamide 1 Gm/M2 each month for six months; from 1978 through June, 1980, adjuvant chemotherapy consisted of cis-platinum 100 mg/M2 each month for four months with the exception of 1 patient treated more aggressively with combination chemotherapy (CISCA). Since July, 1980, a prospective study has been utilized in which patients were randomized into two groups, Group A receiving combination chemotherapy and Group B followed up expectantly; adjuvant chemotherapy appears to result in a slight delay in time to relapse but no influence in overall survival was observed.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.

PubMed

Shimizu, Fumitaka; Muto, Satoru; Taguri, Masataka; Ieda, Takeshi; Tsujimura, Akira; Sakamoto, Yoshiro; Fujita, Kazuhiko; Okegawa, Takatsugu; Yamaguchi, Raizo; Horie, Shigeo

2017-05-01

To evaluate the clinical benefit of adjuvant platinum-based chemotherapy after radical cystectomy for muscle-invasive bladder cancer in routine clinical practice. The present observational study was carried out to compare the effectiveness of adjuvant chemotherapy versus observation post-radical cystectomy in patients with clinically muscle-invasive bladder cancer. Cancer-specific survival and overall survival between the adjuvant chemotherapy group and radical cystectomy alone group were compared using Kaplan-Meier method and log-rank test. After adjusting for background factors using propensity score weighting, differences in cancer-specific survival and overall survival between these two groups were compared. Subgroup analyses by the pathological characteristics were carried out. In total, 322 patients were included in the present study. Of these, 23% received adjuvant chemotherapy post-radical cystectomy. Clinicopathological characteristics showed that patients in the adjuvant chemotherapy group were pathologically more advanced and were at higher risk than the radical cystectomy alone group. In the unadjusted population, although it is not significant, the adjuvant chemotherapy group had lower overall survival (3-year overall survival; 61.5% vs 73.6%, HR 1.33, P = 0.243, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). In the weighted propensity score analysis, although it is not significant, the adjuvant chemotherapy group were superior to radical cystectomy alone groups (overall survival: HR 0.65, 95% CI 0.39-1.09, P = 0.099, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). Subgroup analyses showed that adjuvant chemotherapy significantly reduced the hazard ratio of overall survival and cancer-specific survival in the ≥pT3, pN+, ly+ and v+ subgroups. Platinum-based adjuvant chemotherapy might be associated with increased cancer-specific survival and overall survival in patients with high-risk invasive bladder cancer. �

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

PubMed

Bogani, Giorgio; Fucà, Giovanni; Maltese, Giuseppa; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Lecce, Francesca; Raspagliesi, Francesco; Lorusso, Domenica

2016-11-01

We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested. Copyright © 2016 Elsevier Inc. All rights reserved.

Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature.

PubMed

Alam, Naveed; Shepherd, Frances A; Winton, Timothy; Graham, Barbara; Johnson, David; Livingston, Robert; Rigas, James; Whitehead, Marlo; Ding, Keyue; Seymour, Lesley

2005-03-01

Resected non-small cell lung cancer (NSCLC) has 5-years survival rates of 30-70%. The role of adjuvant chemotherapy remains unclear with poor compliance reported in most trials. The compliance with adjuvant chemotherapy (ACT) for stage IB and II NSCLC was analyzed using data from a North American multi-centre phase III study (accrual 1994-2001) that compared adjuvant chemotherapy to observation. Planned chemotherapy consisted of cisplatin (CIS) 50 mg/m2 days 1, 8 and vinorelbine (VIN) 25 mg/m2 days 1, 8, 15, 22 for four cycles; the VIN dose had been reduced from 30 mg/m2 after an initial cohort of patients experienced unacceptable toxicity. Four hundred and twenty-four patients were randomized after the amendment, 215 to the chemotherapy arm. Median age was 60 years, 64% were male and 84% had stage II disease. Thirty-seven patients completed one cycle, 14 completed two, 20 completed three and 108 patients completed all four cycles. Ten patients received no therapy. Multivariate analysis demonstrated statistically significant differences in compliance with extent of surgery, gender and age. Patients randomized in Canada were more likely to fail to complete chemotherapy due to refusal of therapy than their American counterparts. Patients who had pneumonectomies were more likely to discontinue therapy due to toxicity than those who had lesser resections. Extent of surgery may play a role in both the compliance and toxicity of ACT. Differences between nations in the perception of the risks and benefits of adjuvant chemotherapy regimens, both between physicians and patients, should be investigated further.

Questionnaire survey on adjuvant chemotherapy for elderly patients after gastrectomy indicates their vulnelabilities.

PubMed

Tanahashi, Toshiyuki; Yoshida, Kazuhiro; Yamaguchi, Kazuya; Okumura, Naoki; Takeno, Atsushi; Fujitani, Kazumasa; Fukushima, Norimasa; Takiguchi, Nobuhiro; Nishida, Yasunori; Boku, Narikazu; Yoshikawa, Takaki; Terashima, Masanori

2018-05-24

In Japan, S-1 adjuvant chemotherapy for 1 year is the standard of care for the treatment of stage II and III patients under 80 years old with gastric cancer after curative operation. However, the feasibility of S-1 chemotherapy in patients over 80 years old has not yet been elucidated. To clarify the current treatment situation and feasibility of S-1 treatment in patients over 80 years old, a questionnaire survey of the patients treated from January 2011 to December 2012 was conducted at 58 member institutions of the Stomach Cancer Study Group of the JCOG (Japan Clinical Oncology Group). Gastrectomy was performed in 15,573 patients of all ages, and 1,660 (10.7%) patients were over 80 years of age. Of these elderly patients, 661 (4.2%) were diagnosed as stage II and III. While S-1 adjuvant chemotherapy was recommended to 248 (37.5%) of the stageII/III patients, only 99 (15.0%) of them actually received S-1. Interestingly, the creatinine clearance rate was between 30 and 80 mL/min in 87 (87.9%) of the patients suggesting that S-1 dose modification should be considered. Moreover, S-1 compliance was poor in patients with more than 15% body weight loss. In general practice, surgery alone can be regarded as the standard of care for stage II and III gastric cancer patients over 80 years old. The feasibility and efficacy of S-1 adjuvant chemotherapy should be elucidated in a randomized control trial considering the vulnerabilities of the elderly.

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

PubMed

Schmitt, Thomas; Lehner, Burkhard; Kasper, Bernd; Bischof, Marc; Roeder, Falk; Dietrich, Sascha; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G; Mechtersheimer, Gunhild; Wuchter, Patrick; Ho, Anthony D; Egerer, Gerlinde

2011-12-07

data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account. ClinicalTrials.gov NCT01382030, EudraCT 2004-002501-72. NCT01382030

11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial.

PubMed

Cameron, David; Piccart-Gebhart, Martine J; Gelber, Richard D; Procter, Marion; Goldhirsch, Aron; de Azambuja, Evandro; Castro, Gilberto; Untch, Michael; Smith, Ian; Gianni, Luca; Baselga, Jose; Al-Sakaff, Nedal; Lauer, Sabine; McFadden, Eleanor; Leyland-Jones, Brian; Bell, Richard; Dowsett, Mitch; Jackisch, Christian

2017-03-25

Clinical trials have shown that trastuzumab, a recombinant monoclonal antibody against HER2 receptor, significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer, but long-term follow-up data are needed. We report the results of comparing observation with two durations of trastuzumab treatment at a median follow-up of 11 years, for patients enrolled in the HERA (HERceptin Adjuvant) trial. HERA (BIG 1-01) is an international, multicentre, open-label, phase 3 randomised trial of 5102 women with HER2-positive early breast cancer, who were enrolled from hospitals in 39 countries between Dec 7, 2001, and June 20, 2005. After completion of all primary therapy (including, surgery, chemotherapy, and radiotherapy as indicated), patients were randomly assigned (1:1:1) to receive trastuzumab for 1 year (once at 8 mg/kg of bodyweight intravenously, then 6 mg/kg once every 3 weeks) or for 2 years (with the same dose schedule), or to the observation group. Primary endpoint is disease-free survival, and analyses are in the intention-to-treat population. Hazard ratios (HRs) were estimated from Cox models, and survival curves were estimated by the Kaplan-Meier method. Comparison of 2 years versus 1 year of trastuzumab is based on 366-day landmark analyses. This study is registered with ClinicalTrials.gov (NCT00045032). Of the 5102 women randomly assigned in the HERA trial, three patients had no evidence of having provided written informed consent to participate. We followed up the intention-to-treat population of 5099 patients (1697 in observation, 1702 in 1-year trastuzumab, and 1700 in 2-years trastuzumab groups). After a median follow-up of 11 years (IQR 10·09-11·53), random assignment to 1 year of trastuzumab significantly reduced the risk of a disease-free survival event (HR 0·76, 95% CI 0·68-0·86) and death (0·74, 0·64-0·86) compared with observation. 2 years of adjuvant trastuzumab did not improve disease free

Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer

PubMed Central

Jover, R; Zapater, P; Castells, A; Llor, X; Andreu, M; Cubiella, J; Piñol, V; Xicola, R M; Bujanda, L; Reñé, J M; Clofent, J; Bessa, X; Morillas, J D; Nicolás‐Pérez, D; Payá, A; Alenda, C

2006-01-01

Aim Some retrospective studies have shown a lack of benefit of 5‐fluorouracil (5‐FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5‐FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival. Methods We included 754 patients with a median follow up of 728.5 days (range 1–1097). A total of 260 patients with stage II or III tumours received 5‐FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT‐26 showed instability or there was loss of MLH1 or MSH2 protein expression. Results At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5‐FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non‐chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non‐chemotherapy 82.4%; log rank, p = 0.4). Conclusions Benefit from 5‐FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5‐FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours. PMID:16299036

Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer.

PubMed

Angitapalli, Revathi; Litwin, Alan M; Kumar, Prasanna R G; Nasser, Eiad; Lombardo, Jeffrey; Mashtare, Terry; Wilding, Gregory E; Fakih, Marwan G

2009-01-01

The impact of adjuvant chemotherapy on hepatic function and portal hypertension in patients with stages II-III colon cancer has not been previously described. We conducted a retrospective study to assess the effects of adjuvant FOLFOX chemotherapy on the splenic index (SI) as a surrogate marker for portal hypertension. Stage II-III colorectal cancer patients treated with adjuvant FOLFOX or fluorouracil/leucovorin (5-FU/LV) at Roswell Park Cancer Institute between 2002 and 2006 were identified. Computerizedt omography (CT) scans obtained prior to and at completion of chemotherapy, and every 6 months thereafter were reviewed. Splenic size was evaluated using the SI (SI = length x width x height of the spleen). 40 patients were identified in the FOLFOX group and 23 in the 5-FU/LV group. After 6 months of adjuvant chemotherapy, the mean increase in SI was 45.7 and 16.3% in the FOLFOX and 5-FU/LV groups, respectively (p = 0.0069). SI increased by >100% in 6 patients (15%) in the FOLFOX group versus none in the 5-FU/LV group (p = 0.16). The mean SI at completion of adjuvant chemotherapy was significantly higher in the FOLFOX group than in the 5-FU/LV group (p = 0.007). The mean SI decreased steadily over a period of 2 years after discontinuation of FOLFOX, suggesting potential reversibility of oxaliplatin-induced hepatic injury in this setting. Adjuvant FOLFOX significantly increases the SI in patients with resected colorectal cancer in comparison to adjuvant 5-FU/LV. The increase in SI may be a marker of oxaliplatin-induced hepatic injury and should be investigated further in prospective longitudinal studies of oxaliplatin-based adjuvant chemotherapy. Copyright 2009 S. Karger AG, Basel.

[Role of Pharmacists in Completion of Adjuvant Cisplatin-Vinorelbine Chemotherapy in Japanese Patients with Non-small Cell Lung Cancer].

PubMed

Morimoto, Yoshihito; Takei, Hidefumi; Tachibana, Keisei; Nakazato, Yoko; Tanaka, Ryota; Nagashima, Yasushi; Watanabe, Kazuhiro; Seki, Reisuke; Shinohara, Takao; Kondo, Haruhiko

2018-01-01

　Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m 2 on day 1 and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.

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

van Waart, Hanna; Stuiver, Martijn M; van Harten, Wim H; Sonke, Gabe S; Aaronson, Neil K

2010-12-07

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. 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. 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. This study is registered at the Netherlands Trial Register (NTR 2159).

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

PubMed

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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.

Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer.

PubMed

Tangjitgamol, Siriwan; Katanyoo, Kanyarat; Laopaiboon, Malinee; Lumbiganon, Pisake; Manusirivithaya, Sumonmal; Supawattanabodee, Busaba

2014-12-03

Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT). However, less than two-thirds of patients in this group survive for longer than five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field. However, inconsistency in trial design, inclusion criteria for participants, interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer (LACC). To evaluate the effect of adjuvant chemotherapy (ACT) after concurrent chemoradiation (CCRT) on survival of women with locally advanced cervical cancer compared with CCRT alone. We searched the Cochrane Gynaecological Review Group Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and conference proceedings to March 2014. We handsearched citation lists of relevant studies. Randomised controlled trials (RCTs) comparing CCRT alone versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma, adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma. Two review authors (ST, KK) selected relevant trials, extracted data, assessed risk of bias independently, compared results and resolved disagreements by discussion. We identified two RCTs involving 978 women with cervical cancer stage IIB to IVA. As the trials were significantly different clinically, we did not perform meta-analyses. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall

Efficacy of temozolomide as adjuvant chemotherapy after postsurgical radiotherapy alone for glioblastomas.

PubMed

Rhee, Deok-Joo; Kong, Doo-Sik; Kim, Won Seog; Park, Kwon-Byong; Lee, Jung-Il; Suh, Yeon-Lim; Song, Sang Young; Kim, Sung Tae; Lim, Do-Hoon; Park, Kwan; Kim, Jong Hyun; Nam, Do-Hyun

2009-11-01

The aim of this study was to assess the efficacy of adjuvant TMZ chemotherapy for newly diagnosed GBM patients who were treated with surgery followed by radiotherapy alone. Between January 2003 and April 2005, 59 consecutive GBM patients underwent radiation therapy after surgical resection and subsequently received TMZ chemotherapy. For the comparative analysis, we selected 60 clinically matched GBM patients who underwent radiotherapy followed by nitrosourea-based chemotherapy (NUBC), at the same institution between June 1995 and April 2005. The study cohort was divided into two groups, those with adjuvant TMZ treatment and with NUBC. 59 patients with adjuvant TMZ treatment were assigned to the treatment group and 60 patients with NUBC to the control group. The median overall survival for the treatment group was 18.2 months (95% CI, 11.7-24.7 months), compared with the survival of 14.5 months (95% CI, 11.2-17.7 months) for the control group (p=0.019). The progression-free survival for the treatment group was 5.6 months (95% CI, 4.4-6.7 months), while the control group showed progression-free survival of 3.3 months (95% CT, 3.2-6.0 months) (p=0.030). Uni- and multivariate analysis revealed that extent of surgical resection, age > or =55 years and postoperative KPS were significantly associated with survival. Adjuvant TMZ chemotherapy provided a clinically relevant benefit of survival, as compared with NUBC. Thus, we suggest that adjuvant TMZ chemotherapy may be effective even for patients who did not receive concomitant chemoradiotherapy for GBM.

Adjuvant chemotherapy and whole abdominal irradiation for gastric carcinoma.

PubMed

Kundel, Yulia; Levitt, Mark L; Oberman, Bernice; Sadezki, Siegal; Tichler, Thomas; Symon, Zvi; Catane, Raphael; Pfeffer, Raphael; Brenner, Baruch

2008-01-01

To analyze the efficacy and toxicity of adjuvant chemotherapy followed by whole abdominal irradiation in the treatment of resectable gastric cancer with positive lymph nodes. Between 1996 and 1999, 10 patients with node-positive gastric cancer underwent complete gross resection and were treated by postoperative chemoradiotherapy. The chemotherapy regimen consisted of 5-fluorouracil, 1000 mg/m2/day as a 96-hr continuous infusion on day 1, and cisplatin, 100 mg/m2 on day 2, every 21 days. Six courses were planned. Radiotherapy was administered 3 weeks after completion of the chemotherapy protocol as a single-fraction dose of 600 cGy in a two-field (anterior and posterior) configuration. Treatment was generally well tolerated, with no treatment-related deaths. However, 9 of the 10 patients died of recurrent disease, with a median survival of 20 months (range, 7-84). Adjuvant chemotherapy with whole abdominal irradiation for gastric cancer is safe and tolerable but has no apparent effect on patient outcome. Studies in larger series are needed to evaluate the role of the approach in this disease.

Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer.

PubMed

Munster, Pamela N; Moore, Amy P; Ismail-Khan, Roohi; Cox, Charles E; Lacevic, Mensura; Gross-King, Margaret; Xu, Ping; Carter, W Bradford; Minton, Susan E

2012-02-10

Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.

Impact of liposomal doxorubicin-based adjuvant chemotherapy on autonomy in women over 70 with hormone-receptor-negative breast carcinoma: A French Geriatric Oncology Group (GERICO) phase II multicentre trial.

PubMed

Brain, Etienne G C; Mertens, Cécile; Girre, Véronique; Rousseau, Frédérique; Blot, Emmanuel; Abadie, Sophie; Uwer, Lionel; Bourbouloux, Emmanuelle; Van Praagh-Doreau, Isabelle; Mourey, Loic; Kirscher, Sylvie; Laguerre, Brigitte; Fourme, Emmanuelle; Luneau, Sylvia; Genève, Jean; Debled, Marc

2011-10-01

Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients' autonomy. In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or "high risk" pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete. Forty patients (median age 75 [70-82]) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred. This study demonstrates the feasibility of an adjuvant chemotherapy

Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer

PubMed Central

Kotaka, Masahito; Yamanaka, Takeharu; Yoshino, Takayuki; Manaka, Dai; Eto, Tetsuya; Hasegawa, Junichi; Takagane, Akinori; Nakamura, Masato; Kato, Takeshi; Munemoto, Yoshinori; Nakamura, Fumitaka; Bando, Hiroyuki; Taniguchi, Hiroki; Gamoh, Makio; Shiozawa, Manabu; Saji, Shigetoyo; Maehara, Yoshihiko; Mizushima, Tsunekazu; Ohtsu, Atsushi; Mori, Masaki

2018-01-01

Background The International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3). Patients and methods ACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator. Results Between August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048). Conclusions We confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs. Trial registration number UMIN000008543, Results. PMID:29713499

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial

PubMed Central

2014-01-01

Background Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. Methods/Design In a double–blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Discussion Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms

Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study.

PubMed

Arakawa, K; Kawai, K; Tanaka, T; Hata, K; Sugihara, K; Nozawa, H

2018-05-12

Clinical guidelines recommend adjuvant chemotherapy for high-risk patients with Stage II-III colorectal cancer. However, chemotherapeutic administration rates differ significantly between hospitals. We assessed the prognostic benefit of adjuvant chemotherapy in patients with Stage IIb/c colorectal cancer, and the prognostic impact of interhospital variations in the administration of adjuvant chemotherapy for Stage II-III colorectal cancer. We conducted a multicentre, retrospective study of 17 757 patients with Stage II-III colorectal cancer treated between 1997 and 2008 in 23 hospitals in Japan. Hospitals were classified as high-rate (rate > 42.8%) or low-rate (rate ≤ 42.8%), chemotherapy prescribing clinics. The 5-year overall survival (OS) of patients with Stage II-III colorectal cancer receiving adjuvant chemotherapy was significantly higher than for those not receiving adjuvant chemotherapy (85.7% vs 79.2%, P < 0.01 and 79.9% vs 72.5%, P < 0.01, respectively). For patients with Stage II disease, adjuvant chemotherapy was an independent factor for longer OS (P < 0.01, hazard ratio = 0.71). Both adjuvant chemotherapy and high-rate hospital independently improved OS for patients with Stage III colorectal cancer (both P < 0.01; hazard ratio = 0.68 and 0.87, respectively). Significant prognostic benefit was found for patients with Stage IIb/c colorectal cancer who received adjuvant chemotherapy, with patients who were treated in hospitals with high adjuvant chemotherapy rates demonstrating better prognoses. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Adjuvant chemotherapy in 780 patients with early breast cancer: 10-year data from Saudi Arabia.

PubMed

Ibrahim, Ezzeldin M; Ezzat, Adnan A; Rahal, Mohammed M; Raja, Madras M; Ajarim, Dahish S

2005-01-01

By and large, data about adjuvant chemotherapy for breast cancer in the Middle East are lacking. Retrospective analysis of prospectively captured data from a main referral center in the Kingdom of Saudi Arabia (KSA) may shed some light on the clinicopathological features and survival of patients offered adjuvant chemotherapy in a similar population in that part of the world. Data on patients with invasive breast cancer (Stages I to IIIA) seen between 1992 and the end of 2001 and who received adjuvant chemotherapy were analyzed. A total of 780 patients were considered eligible and constitute the basis of this report. The median age +/- SD of the 780 patients was 42 +/- 9.6 yr. The majority of patients were younger than 50 yr (78%) and premenopausal (83%). Ten percent, 69%, and 21% of patients had Stage I, II, and IIIA, respectively. Patients expressed relatively high prevalence of adverse clinicopathological characteristics. Most patients (523 patients, 67%) received anthracyclines-containing adjuvant chemotherapy, 610 patients (78%) received adjuvant radiotherapy, and 296 (38%) received adjuvant tamoxifen. At a median follow-up of 42 mo (95% CI, 38.1-62.8 mo), the median overall (OS) and disease-free survival (DFS) were not reached; however, the 5-yr actuarial survival was estimated as 74% and 59%, respectively. Cox proportional regression hazard model identified positive axillary nodal status, and positive vascular invasion are the only variables that influenced OS adversely. The model also distinguished the same variables plus negative estrogen receptor status as covariates with negative effect on DFS. In conclusion, this series of 780 predominantly young patients with breast cancer receiving adjuvant chemotherapy highlighted the disease patterns and survival outcome in the KSA. The current series is significant being one of the few reports about adjuvant chemotherapy experience in a developing country and certainly the first from that part of the world.

Adjuvant chemotherapy and overall survival in adult medulloblastoma.

PubMed

Kann, Benjamin H; Lester-Coll, Nataniel H; Park, Henry S; Yeboa, Debra N; Kelly, Jacqueline R; Baehring, Joachim M; Becker, Kevin P; Yu, James B; Bindra, Ranjit S; Roberts, Kenneth B

2017-02-01

Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or older receiving adjuvant chemotherapy for early breast cancer.

PubMed

Adjogatse, D; Thanopoulou, E; Okines, A; Thillai, K; Tasker, F; Johnston, S R D; Harper-Wynne, C; Torrisi, E; Ring, A

2014-11-01

Low rates of adjuvant chemotherapy use are frequently reported in older women with early breast cancer. One of the reasons for this may be the risk of febrile neutropaenia or the perception that older patients will probably not complete the chemotherapy course prescribed. There are no data regarding these adverse outcomes in routine clinical practice. We identified 128 patients aged 70 years or over who received neoadjuvant or adjuvant chemotherapy for early breast cancer in seven UK cancer centres between 2006 and 2012. Data were collected regarding standard clinical and pathological variables and treatment toxicity and outcomes. Twenty-four patients (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not complete their planned therapy. Chemotherapy discontinuation was more common in those patients with an episode of febrile neutropaenia (46% versus 16%, P = 0.004). Thirty patients (23%) were admitted with chemotherapy-related complications. There were no treatment-related deaths. The rates of febrile neutropaenia and treatment discontinuation are high in women aged 70 years or over receiving adjuvant chemotherapy for breast cancer. Close attention should be paid to the choice or regimen and the use of supportive therapies in this patient population. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting.

PubMed

Blohmer, J U; Rezai, M; Kümmel, S; Kühn, T; Warm, M; Friedrichs, K; Benkow, A; Valentine, W J; Eiermann, W

2013-01-01

The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. Country-specific data on the risk of distant recurrence and quality-of-life were not available. Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current

Randomized Trial Using Gonadotropin-Releasing Hormone Agonist Triptorelin for the Preservation of Ovarian Function During (Neo)Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Munster, Pamela N.; Moore, Amy P.; Ismail-Khan, Roohi; Cox, Charles E.; Lacevic, Mensura; Gross-King, Margaret; Xu, Ping; Carter, W. Bradford; Minton, Susan E.

2012-01-01

Purpose Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. Patients and Methods Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. Results Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. Conclusion When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group. PMID:22231041

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial.

PubMed

Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; Vitetta, Luis; McKavanagh, Daniel; Thomson, Damien; Sali, Avni; Isenring, Liz

2014-04-09

Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. In a double-blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this

Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers

PubMed Central

Kim, Jung Ho; Bae, Jeong Mo; Oh, Hyeon Jeong; Lee, Hye Seung; Kang, Gyeong Hoon

2015-01-01

Background: Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability–high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. Methods: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). Results: Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin–based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin–based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. Conclusions: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC. PMID:26148739

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.

PubMed Central

Saarto, T.; Blomqvist, C.; Rissanen, P.; Auvinen, A.; Elomaa, I.

1997-01-01

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy. PMID:9010042

Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

PubMed

Chung, Ki-Young Y; Kelsen, David

2006-06-01

The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

PubMed

Sandra-Petrescu, Flavius; Herrle, Florian; Burkholder, Iris; Kienle, Peter; Hofheinz, Ralf-Dieter

2018-04-03

A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p < 0.0001). Of 361 patients with an overall survival of at least six months, 251(69.5%) patients received all cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

Cost-utility analysis of adjuvant chemotherapy in patients with stage III colon cancer in Thailand.

PubMed

Lerdkiattikorn, Panattharin; Chaikledkaew, Usa; Lausoontornsiri, Wirote; Chindavijak, Somjin; Khuhaprema, Thirawud; Tantai, Narisa; Teerawattananon, Yot

2015-01-01

In Thailand, there has been no economic evaluation study of adjuvant chemotherapy for stage III colon cancer patients after resection. This study aims to evaluate the cost-utility of all chemotherapy regimens currently used in Thailand compared with the adjuvant 5-fluorouracil/leucovorin (5-FU/LV) plus capecitabine as the first-line therapy for metastatic disease in patients with stage III colon cancer after resection. A cost-utility analysis was performed to estimate the relevant lifetime costs and health outcomes of chemotherapy regimens based on a societal perspective using a Markov model. The results suggested that the adjuvant 5-FU/LV plus capecitabine as the first-line therapy for metastatic disease would be the most cost-effective chemotherapy. The adjuvant FOLFOX and FOLFIRI as the first-line treatment for metastatic disease would be cost-effective with an incremental cost-effectiveness ratio of 299,365 Thai baht per QALY gained based on a societal perspective if both prices of FOLFOX and FOLFIRI were decreased by 40%.

Cost-effectiveness of the 21-gene assay for guiding adjuvant chemotherapy decisions in early breast cancer.

PubMed

Paulden, Mike; Franek, Jacob; Pham, Ba'; Bedard, Philippe L; Trudeau, Maureen; Krahn, Murray

2013-01-01

Adjuvant chemotherapy decisions in early breast cancer are complex. The 21-gene assay can potentially aid such decisions, but costs US $4175 per patient. Adjuvant! Online is a freely available decision aid. We evaluate the cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant! Online, and of providing adjuvant chemotherapy conditional upon risk classification. A probabilistic Markov decision model simulated risk classification, treatment, and the natural history of breast cancer in a hypothetical cohort of 50-year-old women with lymph node-negative, estrogen receptor- and/or progesterone receptor-positive, human epidermal growth factor receptor 2/neu-negative early breast cancer. Cost-effectiveness was considered from an Ontario public-payer perspective by deriving the lifetime incremental cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each strategy, and the probability each strategy is cost-effective, assuming a willingness-to-pay of $50,000 per QALY. The 21-gene assay has an incremental cost per QALY in patients at low, intermediate, or high Adjuvant Online! risk of $22,440 (probability cost-effective 78.46%), $2,526 (99.40%), or $1,111 (99.82%), respectively. In patients at low (high) 21-gene assay risk, adjuvant chemotherapy increases (reduces) costs and worsens (improves) health outcomes. For patients at intermediate 21-gene assay risk and low, intermediate, or high Adjuvant! Online risk, chemotherapy has an incremental cost per QALY of $44,088 (50.59%), $1,776 (77.65%), or $1,778 (82.31%), respectively. The 21-gene assay appears cost-effective, regardless of Adjuvant! Online risk. Adjuvant chemotherapy appears cost-effective for patients at intermediate or high 21-gene assay risk, although this finding is uncertain in patients at intermediate 21-gene assay and low Adjuvant! Online risk. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights

Alternative Therapy and Abnormal Liver Function During Adjuvant Chemotherapy in Breast Cancer Patients

PubMed Central

Ahn, Jin-Hee; Kim, Sung-Bae; Yun, Mi Ra; Lee, Jung-Shin; Kang, Yoon-Koo

2004-01-01

Although hepatotoxicity has been rarely reported during adjuvant chemotherapy in breast cancer patients, we observed a high frequency in our patients who were also taking alternative agents. We therefore sought to determine the association between hepatotoxicity and alternative agents during adjuvant chemotherapy in breast cancer patients. All breast cancer patients were treated with the same chemotherapeutic regimen and had normal baseline liver function test (LFT). LFT was checked repeatedly during each cycle of chemotherapy. Patients showing LFT abnormalities were asked about use of alternative agents, and, after the end of chemotherapy, a questionnaire was administered to each patient on their use of alternative agents. Of 178 patients, 65 (36.5%) admitted using alternative therapy, and significantly more patients in this group developed LFT abnormalities (37/65, 56.9%) than those who denied taking alternative therapy (25/113, 22.1%, p=0.001). Although LFT abnormalities were mild to moderate and normalized in most patients after cessation of alternative agents, it remained a serious problem in one patient. In conclusion, alternative therapy may be one of the etiologies for abnormal LFT in breast cancer patients receiving adjuvant chemotherapy. PMID:15201506

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.

PubMed

Shigekawa, Takashi; Osaki, Akihiko; Sekine, Hiroshi; Sato, Nobuaki; Kanbayashi, Chizuko; Sano, Hiroshi; Takeuchi, Hideki; Ueda, Shigeto; Nakamiya, Noriko; Sugitani, Ikuko; Sugiyama, Michiko; Shimada, Hiroko; Hirokawa, Eiko; Takahashi, Takao; Saeki, Toshiaki

2015-04-10

for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey.

PubMed

Basaran, Gul; Turhal, Nazım Serdar; Cabuk, Devrim; Yurt, Nevin; Yurtseven, Gul; Gumus, Mahmut; Teomete, Mehmet; Dane, Faysal; Yumuk, Perran Fulden

2011-06-01

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases

Adjuvant chemotherapy in elderly patients with primary breast cancer: are women ≥65 undertreated?

PubMed

Wallwiener, C W; Hartkopf, A D; Grabe, E; Wallwiener, M; Taran, F-A; Fehm, T; Brucker, S Y; Krämer, B

2016-08-01

To establish whether women over 65 years of age with newly diagnosed with breast cancer (BC) receive adjuvant chemotherapy less frequently than younger postmenopausal women and whether comorbidity influences this potential undertreatment. In a single-site, retrospective, comparative study, postmenopausal early stage BC patients treated between 01/2001 and 12/2005 at a major German university hospital were analyzed in two age Groups A and B (≥65 vs. <65 years) for initiation and completion of guideline-recommended adjuvant chemotherapy. Risk stratification was based on the 2005 St. Gallen Consensus Conference criteria. Comorbidity was parametrized using the Charlson Comorbidity Index (CCI). Analysis included 634 patients, 380 in Group A and 254 in Group B. Mean age (range) was 73 (65-94) and 61 (55-64) years, respectively. The proportion of patients from Group A given ≥3 cycles of chemotherapy was significantly decreased as compared to Group B. 52 % of patients with CCI <3 but only 20 % with CCI ≥3 were recommended to undergo chemotherapy (p < 0.001). Median follow-up [95 % confidence interval (CI)] was 85 (82-88) months. DFS was significantly shorter in patients aged ≥65 years as compared to younger postmenopausal patients (HR, 0.598; 95 % CI, 0.358-0.963; p = 0.048). Despite being high-risk patients, older women with early stage BC were often not given guideline-recommended chemotherapy. Higher recurrence rates compared with younger postmenopausal women suggest that older patients are undertreated. Treatment needs to be adapted to general health and tumor biology rather than age. More trials in elderly BC patients are needed.

The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: Prospective Combined Analysis of Phase III Trials Investigating Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial Design and Current Status.

PubMed

André, Thierry; Iveson, Timothy; Labianca, Roberto; Meyerhardt, Jeffrey A; Souglakos, Ioannis; Yoshino, Takayuki; Paul, James; Sobrero, Alberto; Taieb, Julien; Shields, Anthony F; Ohtsu, Atsushi; Grothey, Axel; Sargent, Daniel J

2013-01-01

The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration was established to prospectively combine and analyze data from several randomized trials conducted around the world to answer whether a three-month course of oxaliplatin-based adjuvant therapy (FOLFOX4/modified FOLFOX6 or XELOX) is non-inferior to the current standard six-month treatment for patients with stage III colon cancer, with a primary endpoint of three years disease-free survival. The IDEA steering committee comprises two members from each group coordinating an individual trial and two members from a secretariat who coordinate combining of the data and management of the joint analysis. Members of the IDEA agreed to combine the data from their individual trials to enable definitive analysis consisting of at least 10,500 patients. With accrual of 8,797 patients at the end of February 2013, the IDEA is on track to achieve its accrual objective of at least 10,500 patients by the end of 2013.

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

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PubMed

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

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. 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. 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). 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. Copyright © 2014 Elsevier Inc. All rights reserved.

Adjuvant trastuzumab with chemotherapy is effective in women with small, node-negative, HER2-positive breast cancer.

PubMed

McArthur, Heather L; Mahoney, Kathleen M; Morris, Patrick G; Patil, Sujata; Jacks, Lindsay M; Howard, Jane; Norton, Larry; Hudis, Clifford A

2011-12-15

Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted. Women with ≤ 2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥ 2) breast cancer were identified through an institutional database. A "no-trastuzumab" cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a "trastuzumab" cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods. The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the "no trastuzumab" and "trastuzumab" cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the "no trastuzumab" cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the "trastuzumab" cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the "no trastuzumab" and "trastuzumab" cohorts, respectively. Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy. Copyright © 2011 American Cancer Society.

Risk of treatment related death and febrile neutropaenia with taxane-based adjuvant chemotherapy for breast cancer in a middle income country outside a clinical trial setting.

PubMed

Phua, Chee Ee; Bustam, Anita Zarina; Yusof, Mastura Md; Saad, Marniza; Yip, Cheng-Har; Taib, Nor Aishah; Ng, Char Hong; Teh, Yew Ching

2012-01-01

The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L. A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: Final results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouesse, Jacques; Lande, Brigitte de la; Bertheault-Cvitkovic, Frederique

Purpose: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. Methods and Materials: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m{sup 2} 5-fluorouracil, 12 mg/m{sup 2} mitoxantrone, and 500 mg/m{sup 2} cyclophosphamide, with concomitant radiotherapy (50 Gy {+-} 10-20-Gy boost). Patients in Arm B received 500 mg/m{sup 2} 5-fluorouracil, 60 mg/m{sup 2} epirubicin, and 500 mg/m{sup 2} cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Results: Medianmore » treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). Conclusions: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.« less

A multigene prognostic assay for selection of adjuvant chemotherapy in patients with T3, stage II colon cancer: impact on quality-adjusted life expectancy and costs.

PubMed

Hornberger, John; Lyman, Gary H; Chien, Rebecca; Meropol, Neal J

2012-12-01

Uncertainty exists regarding appropriate and affordable use of adjuvant chemotherapy in stage II colon cancer (T3, proficient DNA mismatch repair). This study aimed to estimate the effectiveness and costs from a US societal perspective of a multigene recurrence score (RS) assay for patients recently diagnosed with stage II colon cancer (T3, proficient DNA mismatch repair) eligible for adjuvant chemotherapy. RS was compared with guideline-recommended clinicopathological factors (tumor stage, lymph nodes examined, tumor grade, and lymphovascular invasion) by using a state-transition (Markov) lifetime model. Data were obtained from published literature, a randomized controlled trial (QUick And Simple And Reliable) of adjuvant chemotherapy, and rates of chemotherapy use from the National Cooperative Cancer Network Colon/Rectum Cancer Outcomes study. Life-years, quality-adjusted life expectancy, and lifetime costs were examined. The RS is projected to reduce adjuvant chemotherapy use by 17% compared with current treatment patterns and to increase quality-adjusted life expectancy by an average of 0.035 years. Direct medical costs are expected to decrease by an average of $2971 per patient. The assay was cost saving for all subgroups of patients stratified by clinicopathologic factors. The most influential variables affecting treatment decisions were projected years of life remaining, recurrence score, and patients' disutilities associated with adjuvant chemotherapy. Use of the multigene RS to assess recurrence risk after surgery in stage II colon cancer (T3, proficient DNA mismatch repair) may reduce the use of adjuvant chemotherapy without decreasing quality-adjusted life expectancy and be cost saving from a societal perspective. These findings need to be validated in additional cohorts, including studies of clinical practice as assay use diffuses into nonacademic settings. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR

The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study.

PubMed

Kawashima, Atsunari; Nakai, Yasutomo; Nakayama, Masashi; Ujike, Takeshi; Tanigawa, Go; Ono, Yutaka; Kamoto, Akihito; Takada, Tsuyosi; Yamaguchi, Yuichiro; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Tsujimura, Akira

2012-10-01

To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required.

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twu, Chih-Wen; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; Wang, Wen-Yi

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.more » 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.« less

The Effect of a Standardized Ginger Extract on Chemotherapy-Induced Nausea-Related Quality of Life in Patients Undergoing Moderately or Highly Emetogenic Chemotherapy: A Double Blind, Randomized, Placebo Controlled Trial.

PubMed

Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; McKavanagh, Dan; Vitetta, Luis; Sali, Avni; Lohning, Anna; Isenring, Elisabeth

2017-08-12

Ginger supplementation could be an effective adjuvant treatment for chemotherapy-induced nausea (CIN). The aim of this clinical trial was to address significant methodological limitations in previous trials. Patients (N = 51) were randomly allocated to receive either 1.2 g of standardised ginger extract or placebo per day, in addition to standard anti-emetic therapy, during the first three cycles of chemotherapy. The primary outcome was CIN-related quality of life (QoL) measured with the Functional Living Index- Emesis (FLIE) questionnaire. Secondary outcomes included acute and delayed nausea, vomiting, and retching as well as cancer-related fatigue, nutritional status, and CIN and vomiting-specific prognostic factors. Over three consecutive chemotherapy cycles, nausea was more prevalent than vomiting (47% vs. 12%). In chemotherapy Cycle 1, intervention participants reported significantly better QoL related to CIN ( p = 0.029), chemotherapy-induced nausea and vomiting (CINV)-related QoL ( p = 0.043), global QoL ( p = 0.015) and less fatigue ( p = 0.006) than placebo participants. There were no significant results in Cycle 2. In Cycle 3, global QoL ( p = 0.040) and fatigue ( p = 0.013) were significantly better in the intervention group compared to placebo. This trial suggests adjuvant ginger supplementation is associated with better chemotherapy-induced nausea-related quality of life and less cancer-related fatigue, with no difference in adverse effects compared to placebo.

Tumor 5-FU-related mRNA Expression and Efficacy of Oral Fluoropyrimidines in Adjuvant Chemotherapy of Colorectal Cancer.

PubMed

Koda, Keiji; Miyauchi, Hideaki; Kosugi, Chihiro; Kaiho, Takashi; Takiguchi, Nobuhiro; Kobayashi, Susumu; Maruyama, Takashi; Matsubara, Hisahiro

2016-10-01

It has not been elucidated whether the clinical efficacy of oral fluoropyrimidines for adjuvant chemotherapy of colorectal cancer varies with tumor biological characteristics. A multicenter randomized trial was performed comparing oral tegafur/gimeracil/oteracil (S-1) and uracil-tegafur/ leucovorin (UFT/LV) as adjuvant therapy for stage III colorectal cancer. Postoperative survival was compared based on the 5-FU-related mRNA levels in cancer tissues. Among patients with tumor expressing dihydropyrimidine dehydrogenase (DPD) mRNA within the 66.7th percentile (lower 2/3) of all cases, overall survival (OS) was significantly better in the S-1 than in the UFT/LV group. In the S-1 group, patients with low DPD-expressing tumors had significantly better OS than those with highly expressing tumors. Patients with low thymidine synthase (TS)-expressing tumors had significantly better OS than those with highly expressing tumors. The efficacy of oral fluoropyrimidines as adjuvant chemotherapy for colorectal cancer may be influenced by the level of 5-FU-related mRNA in cancer tissues. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Preoperative chemotherapy for operable breast cancer is associated with better compliance with adjuvant therapy in matched stage II and IIIA patients.

PubMed

Komenaka, Ian K; Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E; Low, Boo Ghee; Salganick, Jason A; Nodora, Jesse; Hibbard, Michael L; Jha, Chandra

2011-01-01

Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy.

Emergency department presentations in early stage breast cancer patients receiving adjuvant and neoadjuvant chemotherapy.

PubMed

Tang, Monica; Horsley, Patrick; Lewis, Craig R

2018-05-01

(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018). © 2018 Royal Australasian College of Physicians.

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.

[A Case of Advanced Transverse Colon Cancer with Nephrotic Syndrome Treated with Curative Resection and Complete Adjuvant Chemotherapy].

PubMed

Sato, Nobutaka; Fuyuno, Seiya; Hatada, Teppei; Furuhashi, Takashi; Abe, Toshihiko

2017-05-01

A 74-year-old woman was diagnosed as having transverse colon cancer after diagnosis of nephrotic syndrome caused by membranous nephropathy. Although she had hypoproteinemia and hypoalbuminemia, we judged that she had no major nutritional problem. In previous, similar case reports, the use of human serum albumin and fresh-frozen plasma was suggested to be important to avoid complications in the perioperative period. Thus, we used the same in our patient in the perioperative period. In addition, we paid special attention to perioperative nutrition management and used total parenteral nutrition in perioperative period. We performed laparoscopic assisted right hemicolectomy. On the 15th day after the surgical resection, the patient was discharged without any problems. We considered that postoperative adjuvant chemotherapy with XELOX (CapeOX)should be performed because the TNM pathological stage was pStage III b. Regarding adjuvant chemotherapy for gastrointestinal cancer with nephrotic syndrome, no previous reports detailed the indications for postoperative adjuvant chemotherapy. Upon introduction of adjuvant chemotherapy, we determined adaptation in accordance with the general adaptation criteria. While observing the patient's progress with a nephrologist, we safely completed the scheduled 8 courses adjuvant chemotherapy.

A Meta-Analysis of Cognitive Impairment and Decline Associated with Adjuvant Chemotherapy in Women with Breast Cancer

PubMed Central

Ono, Miyuki; Ogilvie, James M.; Wilson, Jennifer S.; Green, Heather J.; Chambers, Suzanne K.; Ownsworth, Tamara; Shum, David H. K.

2015-01-01

A meta-analysis was performed to quantify the magnitude and nature of the association between adjuvant chemotherapy and performance on a range of cognitive domains among breast cancer patients. A total of 27 studies (14 cross-sectional, 8 both cross-sectional and prospective, and 5 prospective) were included in the analyses, involving 1562 breast cancer patients who had undergone adjuvant chemotherapy and 2799 controls that included breast cancer patients who did not receive adjuvant chemotherapy. A total of 737 effect sizes (Cohen’s d) were calculated for cross-sectional and prospective longitudinal studies separately and classified into eight cognitive domains. The mean effect sizes varied across cross-sectional and prospective longitudinal studies (ranging from −1.12 to 0.62 and −0.29 to 1.12, respectively). Each cognitive domain produced small effect sizes for cross-sectional and prospective longitudinal studies (ranging from −0.25 to 0.41). Results from cross-sectional studies indicated a significant association between adjuvant chemotherapy and cognitive impairment that held across studies with varied methodological approaches. For prospective studies, results generally indicated that cognitive functioning improved over time after receiving adjuvant chemotherapy. Greater cognitive impairment was reported in cross-sectional studies comparing chemotherapy groups with healthy control groups. Results suggested that cognitive impairment is present among breast cancer patients irrespective of a history of chemotherapy. Prospective longitudinal research is warranted to examine the degree and persisting nature of cognitive impairment present both before and after chemotherapy, with comparisons made to participants’ cognitive function prior to diagnosis. Accurate understanding of the effects of chemotherapy is essential to enable informed decisions regarding treatment and to improve quality of life among breast cancer patients. PMID:25806355

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

PubMed

Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

2017-05-01

Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

5-Fluorouracil Adjuvant Chemotherapy Does Not Increase Survival in Patients with CpG Island Methylator Phenotype Colorectal Cancer

PubMed Central

Jover, Rodrigo; Nguyen, Thuy-Phuong; Pérez-Carbonell, Lucía; Zapater, Pedro; Payá, Artemio; Alenda, Cristina; Rojas, Estefanía; Cubiella, Joaquín; Balaguer, Francesc; Morillas, Juan D.; Clofent, Juan; Bujanda, Luis; Reñé, Josep M; Bessa, Xavier; Xicola, Rosa M.; Nicolás-Pérez, David; Castells, Antoni; Andreu, Montserrat; Llor, Xavier; Boland, C. Richard; Goel, Ajay

2011-01-01

Background & Aims 5-FU-based adjuvant chemotherapy does not increase survival times of patients with colorectal tumors with microsatellite instability. We determined the response of patients with colorectal tumors with the CpG island methylator phenotype (CIMP) to 5-FU-based therapy. Methods We analyzed a population-based cohort of 302 patients with colorectal cancer (CRC) for a median follow-up time of 50.7 months. CIMP status was determined by analysis of the CACNAG1, SOCS1, RUNX3, NEUROG1, and MLH1 promoters; tumors were considered to be CIMP-positive (CIMP+) if at least 3 promoters were methylated. Results Tumors from 29.5% (89/302) of patients were CIMP+; this did not influence disease-free survival (log rank=.26). Of tumors of TNM stages II–III (n=196), 32.7% were CIMP+. Among patients with CRC stages II–III who did not receive adjuvant 5-FU chemotherapy, those with CIMP+ tumors had longest times of disease-free survival (log rank=.04); patients with CIMP+ tumors who received chemotherapy had shorter times of disease-free survival (log rank=0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy significantly increased time of disease-free survival (log-rank=.00001). However, in patients with CIMP+ tumors, adjuvant 5-FU chemotherapy did not affect time of disease-free survival (log rank=.7). Multivariate analysis showed a significant, independent interaction between 5-FU treatment and CIMP status (hazard ratio [HR]=0.6; 95% confidence interval [CI], .5–.8). Among patients with CIMP+ tumors, adjuvant chemotherapy was not an independent predictor of outcome (HR=0.8; 95% CI, 0.3–2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP status was the only independent predictor of survival (HR=2.0; 95% CI, 1.1–3.8) Conclusion Patients with CIMP+ colorectal tumors do not benefit from 5-FU–based adjuvant chemotherapy. PMID:21185836

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

Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer.

PubMed

Kotaka, Masahito; Yamanaka, Takeharu; Yoshino, Takayuki; Manaka, Dai; Eto, Tetsuya; Hasegawa, Junichi; Takagane, Akinori; Nakamura, Masato; Kato, Takeshi; Munemoto, Yoshinori; Nakamura, Fumitaka; Bando, Hiroyuki; Taniguchi, Hiroki; Gamoh, Makio; Shiozawa, Manabu; Saji, Shigetoyo; Maehara, Yoshihiko; Mizushima, Tsunekazu; Ohtsu, Atsushi; Mori, Masaki

2018-01-01

The International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3). ACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator. Between August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048). We confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs. UMIN000008543, Results.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

PubMed

Feng, Yan-Ru; Jin, Jing; Ren, Hua; Wang, Xin; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Tang, Yuan; Li, Ning; Liu, Xin-Fan; Fang, Hui; Yu, Zi-Hao; Li, Ye-Xiong

2017-03-09

In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m 2 ) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Preoperative Chemotherapy for Operable Breast Cancer Is Associated with Better Compliance with Adjuvant Therapy in Matched Stage II and IIIA Patients

PubMed Central

Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E.; Low, Boo Ghee; Salganick, Jason A.; Nodora, Jesse; Hibbard, Michael L.; Jha, Chandra

2011-01-01

Introduction. Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Methods. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. Results. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. Conclusions. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy. PMID:21558134

The effect of a simultaneous versus a staged resection of metastatic colorectal cancer on time to adjuvant chemotherapy.

PubMed

Le Souder, Emily; Azin, Arash; Wood, Trevor; Hirpara, Dhruvin; Elnahas, Ahmad; Cleary, Sean; Wei, Alice; Walker, Richard; Parsyan, Armen; Chadi, Sami; Quereshy, Fayez

2018-06-07

Patients with colorectal cancer with synchronous liver metastases may undergo a staged or a simultaneous resection. This study aimed to determine whether the time to adjuvant chemotherapy was delayed in patients undergoing a simultaneous resection. A retrospective cohort study was conducted between 2005 and 2016. The primary outcome was time to adjuvant chemotherapy. A multivariate linear regression was conducted to ascertain the adjusted effect of a simultaneous versus a staged approach on time to adjuvant chemotherapy. A total of 155 patients were included. A total of 127 patients underwent a staged resection, whereas 28 patients underwent a simultaneous resection. Age, sex, and American Society of Anesthesiologists class as well tumor, node, metastasis stage, tumor location, and number and size of metastases were not significantly different between the groups. The median time to adjuvant chemotherapy was 70 and 63 days for the staged and simultaneous groups, respectively (P = .27). Multivariate analysis did not demonstrate an increased propensity for prolonged time to chemotherapy after simultaneous resection (rate ratio: 0.97, 95% CI: 0.71-1.32, P = .84). There were no significant differences in the length of stay, complications, overall survival, and disease-free survival between the groups (P > .05). This study demonstrated that simultaneous resection does not result in significant delay of adjuvant chemotherapy compared with a staged approach. © 2018 Wiley Periodicals, Inc.

Adjuvant chemotherapy for locally advanced urothelial carcinoma: an overview of the USC experience.

PubMed

Dorff, Tanya B; Tsao-Wei, Denice; Miranda, Gus; Skinner, Donald G; Stein, John P; Quinn, David I

2009-02-01

To describe the tolerability of two chemotherapy regimens, gemcitabine and cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for adjuvant treatment of patients with locally advanced urothelial cancer after radical cystectomy. The USC Department of Urology bladder cancer database was searched for subjects who received adjuvant chemotherapy following cystectomy for transitional cell carcinoma with extravesical and/or lymph node involvement, yielding 187 cases. Clinical details regarding toxicity, number of cycles administered, and cancer outcome were analyzed. The majority of subjects had lymph node involvement (70%). Sixty-eight percent of subjects received MVAC and 32% received GC, the latter regimen was predominant after 2000. Fifty-six percent of subjects received all four planned cycles (51% GC and 58% MVAC). With a median follow-up of 11.2 years (range 1.9-19.6), 96 patients (51%) have suffered a relapse, with no significant difference between chemotherapy regimens. Median time to recurrence for the population was 3.7 years and median overall survival is 4.6 years (3.0-9.3). The median time from recurrence to death was 6.7 months and was not significantly different between MVAC and GC. Both MVAC and GC are tolerated after cystectomy for advanced urothelial carcinoma. A significant proportion of high-risk patients survive, free of disease, beyond 10 years. At recurrence, patients previously treated with adjuvant chemotherapy have a survival that appears much shorter than patients who develop metastases in the absence of this exposure, suggesting resistance to salvage chemotherapy.

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER-Medicare analysis.

PubMed

Malhotra, J; Mhango, G; Gomez, J E; Smith, C; Galsky, M D; Strauss, G M; Wisnivesky, J P

2015-04-01

The role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly. We identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score. Overall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68-0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction. Platinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy.

PubMed

Yun, J; Kim, K H; Kang, E S; Gwak, G-Y; Choi, M S; Lee, J E; Nam, S J; Yang, J-H; Park, Y H; Ahn, J S; Im, Y-H

2011-02-15

With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy. The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed. From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14%; P=0.04), and less severe hepatitis (0 vs 17%; P=0.002). Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy

PubMed Central

Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

2015-01-01

was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. Trial Registration ClinicalTrials.gov NCT02430974 PMID:26474174

Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs.

PubMed

Wouda, R M; Borrego, J; Keuler, N S; Stein, T

2016-03-01

There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post-operative management of ASAGAC. Seventy-four dogs with naturally occurring ASAGAC underwent surgery. Forty-four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC. © 2013 John Wiley & Sons Ltd.

Adjuvant Chemotherapy for Stage II Right- and Left-Sided Colon Cancer: Analysis of SEER-Medicare Data

PubMed Central

Weiss, Jennifer M.; Schumacher, Jessica; Allen, Glenn O.; Neuman, Heather; Lange, Erin O’Connor; LoConte, Noelle K.; Greenberg, Caprice C.; Smith, Maureen A.

2014-01-01

Purpose Survival benefit from adjuvant chemotherapy is established for stage III colon cancer; however, uncertainty exists for stage II patients. Tumor heterogeneity, specifically microsatellite instability (MSI) which is more common in right-sided cancers, may be the reason for this observation. We examined the relationship between adjuvant chemotherapy and overall 5-year mortality for stage II colon cancer by location (right- versus left-side) as a surrogate for MSI. Methods Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified Medicare beneficiaries from 1992 to 2005 with AJCC stage II (n=23,578) and III (n=17,148) primary adenocarcinoma of the colon who underwent surgery for curative intent. Overall 5-year mortality was examined with Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. Results Eighteen percent (n=2,941) of stage II patients with right-sided cancer and 22% (n=1,693) with left-sided cancer received adjuvant chemotherapy. After adjustment, overall 5-year survival benefit from chemotherapy was observed only for stage III patients (right-sided: HR 0.64; 95% CI, 0.59–0.68, p<0.001 and left-sided: HR 0.61; 95% CI, 0.56–0.68, p<0.001). No survival benefit was observed for stage II patients with either right-sided (HR 0.97; 95% CI, 0.87–1.09, p=0.64) or left-sided cancer (HR 0.97; 95% CI, 0.84–1.12, p=0.68). Conclusions Among Medicare patients with stage II colon cancer, a substantial number receive adjuvant chemotherapy. Adjuvant chemotherapy did not improve overall 5-year survival for either right- or left-sided colon cancers. Our results reinforce existing guidelines and should be considered in treatment algorithms for older adults with stage II colon cancer. PMID:24643898

High-Dose Chemotherapy With Autologous Stem-Cell Support As Adjuvant Therapy in Breast Cancer: Overview of 15 Randomized Trials

PubMed Central

Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Rodenhuis, Sjoerd; Peters, William P.; Leonard, Robert C.; Barlow, William E.; Tallman, Martin S.; Bergh, Jonas; Nitz, Ulrike A.; Gianni, Alessandro M.; Basser, Russell L.; Zander, Axel R.; Coombes, R. Charles; Roché, Henri; Tokuda, Yutaka; de Vries, Elisabeth G.E.; Hortobagyi, Gabriel N.; Crown, John P.; Pedrazzoli, Paolo; Bregni, Marco; Demirer, Taner

2011-01-01

Purpose Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets. Methods We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status. Results Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio [HR], 0.87; 95% CI, 0.81 to 0.93; P < .001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients. Conclusion Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown. PMID:21768471

Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

PubMed

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

2013-01-01

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. 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. 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. 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%. 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 higher value of willingness-to-pay threshold.

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PubMed

Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

2016-01-01

The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

How does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer?

PubMed

Marino, Jennifer L; Saunders, Christobel M; Emery, Laura I; Green, Helena; Doherty, Dorota A; Hickey, Martha

2016-09-01

The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life. Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales. The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12-3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13-3.18), but did not differ in other quality of life measures. In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy.

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Garg, Madhur K.; Aparo, Santiago

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 frommore » 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.« less

Adjuvant treatment of stage IB NSCLC: the problem of stage subset heterogeneity.

PubMed

Calhoun, Royce; Jablons, David; Lau, Derick; Gandara, David R

2008-04-30

While 5-year survival rates in patients with stage IB non-small-cell lung cancer (NSCLC) are historically modest (40% to 67%), adjuvant chemotherapy trials including this subgroup have shown little evidence of chemotherapeutic benefit. This article reviews the available data regarding adjuvant chemotherapy following surgically resected stage IB NSCLC, framed within the context of present and future proposed definitions of this diagnosis. The discussion addresses limitations of the current staging system and how this contributes to the mixed results seen with adjuvant treatment. In addition, the authors consider current treatment options for stage IB NSCLC and review planned clinical trials for stage I disease designed to exploit new pharmacogenomic findings.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

PubMed Central

Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2010-01-01

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer.

PubMed

Sparano, Joseph A; Goldstein, Lori J; Childs, Barrett H; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L; Bugarini, Roberto; Rowley, Steve; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Kenny, Paraic A; Sledge, George W; Gray, Robert

2011-11-15

To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

Relationship Between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple Negative Breast Cancer

PubMed Central

Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Kenny, Paraic A.; Sledge, George W.; Gray, Robert

2012-01-01

Purpose To perform an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental design RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative RT-PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results GRB7 was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn’s adjusted p value=0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR 2.31, p=0.04 using the median as the split). The 5-year recurrence rates were 10.5% (95% confidence intervals [CI] 7.8%, 14.1%) in the low and 20.4% (95% CI 16.5%, 25.0%) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. PMID:21933890

Type of Resection (Whipple vs. Distal) Does Not Affect the National Failure to Provide Post-resection Adjuvant Chemotherapy in Localized Pancreatic Cancer.

PubMed

Bergquist, John R; Ivanics, Tommy; Shubert, Christopher R; Habermann, Elizabeth B; Smoot, Rory L; Kendrick, Michael L; Nagorney, David M; Farnell, Michael B; Truty, Mark J

2017-06-01

Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). The National Cancer Data Base (2004-2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90-1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology.

PubMed

Mamounas, Eleftherios P; Tang, Gong; Paik, Soonmyung; Baehner, Frederick L; Liu, Qing; Jeong, Jong-Hyeon; Kim, S Rim; Butler, Steven M; Jamshidian, Farid; Cherbavaz, Diana B; Sing, Amy P; Shak, Steven; Julian, Thomas B; Lembersky, Barry C; Wickerham, D Lawrence; Costantino, Joseph P; Wolmark, Norman

2018-02-01

The 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen. The B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients > 50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years. In univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (p < 0.001). In the study population (n = 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72-1.05; p = 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69-1.47; p = 0.99), 0.84 (95% CI 0.62-1.14; p = 0.26), and 0.81 (95% CI 0.60-1.10; p = 0.21), respectively (interaction p = 0.64). Similar findings were observed for the other study endpoints. RS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28).

Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. QUASAR Collaborative Group.

PubMed

2000-05-06

Standard adjuvant chemotherapy for colorectal cancer consists of fluorouracil with folinic acid or levamisole. The large QUASAR randomised trial aimed to investigate (in a two x two design) whether use of a higher dose of folinic acid or addition of levamisole to fluorouracil and folinic acid improved survival. Patients with colorectal cancer, without evident residual disease, were randomly assigned fluorouracil (370 mg/m2) with high-dose (175 mg) or low-dose (25 mg) L-folinic acid and either active or placebo levamisole. The fluorouracil and folinic acid could be given either as six 5-day courses with 4 weeks between the start of the courses or as 30 once-weekly doses. Levamisole (50 mg) or placebo was given three times daily for 3 days repeated every 2 weeks for 12 courses. The primary endpoint was mortality from any cause. Analyses were by intention to treat. Between 1994 and 1997, 4,927 patients were enrolled. 1,776 had recurrences and 1,576 died. Survival was similar with high-dose and low-dose folinic acid (70.1% vs 71.0% at 3 years; p=0-43), as were 3-year recurrence rates (36.0% vs 35.8%; p=0.94). Survival was worse with levamisole than with placebo (69.4% vs 71.5% at 3 years; p=0.06), and there were more recurrences with the active drug (37.0% vs 34.9% at 3 years; p=0.16). The inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. Higher-dose folinic acid produced no extra benefit in these regimens over that from low-dose folinic acid. Trials of chemotherapy versus no chemotherapy will show whether these four treatments are equally effective or equally ineffective.

Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

PubMed Central

Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

2015-01-01

Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy.

PubMed

Li, Wentao; Kwok, Carol Chi-Hei; Chan, Dominic Chun-Wan; Wang, Feng; Tse, Lap Ah

2018-04-01

Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. Low levels of percent rhythm (HR:2.59, 95% CI 1.50-4.72), double amplitude (HR:2.70, 95% CI 1.51-4.85), and mesor (HR: 2.48, 95% CI 1.44-4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02-5.69) and double amplitude (HR:2.49, 95% CI 1.05-5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

Efficacy and safety of platinum combination chemotherapy re-challenge for relapsed patients with non-small-cell lung cancer after postoperative adjuvant chemotherapy of cisplatin plus vinorelbine.

PubMed

Imai, Hisao; Shukuya, Takehito; Yoshino, Reiko; Muraki, Keiko; Mori, Keita; Ono, Akira; Akamatsu, Hiroaki; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Tomizawa, Yoshio; Takahashi, Toshiaki; Takahashi, Kazuhisa; Saito, Ryusei; Yamamoto, Nobuyuki

2013-01-01

There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC. © 2014 S. Karger AG, Basel.

Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy.

PubMed

Kriege, M; Hollestelle, A; Jager, A; Huijts, P E A; Berns, E M; Sieuwerts, A M; Meijer-van Gelder, M E; Collée, J M; Devilee, P; Hooning, M J; Martens, J W M; Seynaeve, C

2014-08-26

We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.

Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial.

PubMed

Hong, Yong Sang; Nam, Byung-Ho; Kim, Kyu-Pyo; Kim, Jeong Eun; Park, Seong Joon; Park, Young Suk; Park, Joon Oh; Kim, Sun Young; Kim, Tae-You; Kim, Jee Hyun; Ahn, Joong Bae; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon; Yun, Seong Hyeon; Kim, Jong Hoon; Park, Jin-Hong; Park, Hee Chul; Jung, Kyung Hae; Kim, Tae Won

2014-10-01

The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m(2) and leucovorin 20 mg/m(2) on days 1-5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil bolus 400 mg/m(2) on day 1, and fluorouracil infusion 2400 mg/m(2) for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov, number NCT00807911. Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4-50·6). 3-year disease

Adjuvant Chemotherapy Improves Prostate Cancer Survival

Cancer.gov

Giving some men with prostate cancer chemotherapy after standard treatment with radiation and hormone therapy modestly improves how long they live, according to results from a new NCI-funded clinical trial.

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

PubMed

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

2016-04-05

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.

A randomized trial of adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy for operable breast cancer stratified by estrogen receptors.

PubMed

Nomura, Y; Tashiro, H; Hisamatsu, K; Shinozuka, K

1988-06-01

Based on estrogen receptor (ER) status and menopausal status, operable breast cancer (International Union Against Cancer [UICC] Stage I, II, and III) patients were randomized for adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy, and the effects on the disease-free survival (DFS) and overall survival (OS) were compared. Adjuvant endocrine therapy was composed of tamoxifen (TAM) 20 mg/day orally for 2 years in postmenopausal patients. In premenopausal patients, oophorectomy (OVEX) was done before TAM administration. In the chemotherapy arm, the patients were given 0.06 mg/kg of body weight of mitomycin C (MMC) intravenously (IV) and then an oral administration of cyclophosphamide (CPA) 100 mg/body orally in an administration of a 3-month period and a 3-month intermission. This 6-month schedule was repeated four times in 2 years. As the chemoendocrine therapy arm, TAM with MMC + CPA chemotherapy was added. The patients were randomized according to ER and menopausal status. Estrogen receptor-positive (ER+) cancer patients were randomized to three arms: TAM +/- OVEX, MMC + CPA, or MMC + CPA + TAM. For estrogen receptor-negative (ER-) patients, there were two arms: MMC + CPA, or MMC + TAM. The study started in September 1978, and 692 patients entered until the end of 1984 were evaluated. The median follow-up was about 46 months. Totally, a 9.8% rate (68/692) of recurrence was noted, a 7.5% rate (52/692) of mortality. There were no significant differences in DFS or OS among the treatment arms in ER+ or ER- patients. There was significant differences in adverse effects such as bone marrow suppression, gastrointestinal disturbances, cystitis, hair loss between endocrine therapy and chemotherapy or chemoendocrine therapy groups. In this preliminary study, it was concluded that because of less adverse effects of endocrine therapy, it seems rational to select the operable breast cancer patients by the presence or absence of ER, namely, endocrine therapy for

Perioperative chemotherapy more of a benefit for overall survival than adjuvant chemotherapy for operable gastric cancer: an updated Meta-analysis

PubMed Central

Yang, Ya’nan; Yin, Xue; Sheng, Lei; Xu, Shan; Dong, Lingling; Liu, Lian

2015-01-01

To clarify the effect of neoadjuvant chemotherapy (NAC) on the survival outcomes of operable gastric cancers, we searched PubMed, Embase, and Cochrane Library for randomized clinical trials published until June 2014 that compared NAC-containing strategies with NAC-free strategies in patients with adenocarcinoma of the stomach or the esophagogastric junction, who had undergone potentially curative resection. The adjusted pooled hazard ratio (HR) for overall survival (OS) was insignificant when comparing the NAC-containing arm with the NAC-free arm. Subgroup analysis showed that the OS of the treatment arm that involved both adjuvant chemotherapy (AC) and NAC was significantly improved over the control arm (AC only) (HR = 0.48, 95% CI: 0.35–0.67; P < 0.001). While NAC alone plus surgery did not show any survival benefit over surgery alone. Perioperative chemotherapy (PC) also showed a significant increase in PFS and a significant reduction in distant metastasis compared to surgery alone. Therefore, in patients with resectable gastric cancer, NAC alone is not enough and AC alone is not good enough to definitely improve their OS. Collectively, PC combined with surgery could maximize the survival benefit for patients with resectable gastric cancer. PMID:26242393

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

PubMed

Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

2017-08-15

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017

Why adjuvant chemotherapy for stage III colon cancer was not given: Reasons for non-recommendation by clinicians or patient refusal.

PubMed

Gilbar, Peter; Lee, Andrew; Pokharel, Khageshwor

2017-03-01

Aim The aim of our study was to evaluate stage III colon cancer patients discussed at a multidisciplinary team meeting to identify reasons for clinicians not recommending adjuvant chemotherapy and reasons for patients declining recommended chemotherapy. Methods A retrospective, single institution Australian study was conducted on all surgically managed stage III colon cancer patients diagnosed at the regional cancer centre at Toowoomba Hospital between July 2010 and December 2014. Reasons why adjuvant chemotherapy was not recommended by the multidisciplinary team or following referral to a medical oncologist and patients' reasons for refusing chemotherapy despite medical oncology recommendation were determined. Results One hundred and nine patients were suitable for evaluation. Overall, 72 (66.1%) received adjuvant chemotherapy. Chemotherapy was not recommended in 25 (23.4%) of patients, with the majority (68%) having more than one cited reason. Multiple comorbidities and advanced age were the most common reasons for non-recommendation ( p < 0.01). Age alone was not a reason for not recommending chemotherapy. Twelve (11%) patients declined offered chemotherapy. The reasons for refusal were not detailed in the majority of patient charts (63.6%). Travel distance was not a factor in accepting or refusing chemotherapy. Conclusion Discussion at a multidisciplinary team meeting facilitates the identification of patients unsuitable for adjuvant treatment. The reasons for declining offered chemotherapy need to be assessed fully to ensure that patients' treatment preferences are balanced against the proven benefits of chemotherapy. Attendance at a regional cancer centre provides the opportunity for high standard care in the management of stage III colon cancer.

Association between adjuvant chemotherapy and risk of acute kidney injury in elderly women diagnosed with early-stage breast cancer.

PubMed

Li, Shuling; Liu, Jiannong; Virnig, Beth A; Collins, Allan J

2017-02-01

We studied elderly Medicare enrollees newly diagnosed with early-stage breast cancer to examine the association between adjuvant chemotherapy and acute kidney injury (AKI). Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort study including women diagnosed with stages I-III breast cancer at ages 66-89 years between 1992 and 2007. We performed one-to-one matching on time-dependent propensity score on the day of adjuvant chemotherapy initiation within 6 months after the first cancer-directed surgery based on the estimated probability of chemotherapy initiation at each day for each patient, using a Cox proportional hazards model. We estimated the cumulative incidence of AKI using Kaplan-Meier methods. We used Cox proportional hazards models to evaluate the association between chemotherapy and the risk of AKI, and compared the risk among major chemotherapy types. The study included 28,048 women. The 6-month cumulative incidence of AKI was 0.80% for chemotherapy-treated patients, compared with 0.30% for untreated patients (P < 0.001). Adjuvant chemotherapy was associated with a nearly threefold increased risk of AKI [hazard ratio (HR) 2.73; 95% CI 1.8-4.1]. Compared with anthracycline-based chemotherapy, the HRs (95% CIs) were 1.66 (0.94-2.91), 0.88 (0.53-1.47), and 1.15 (0.57-2.32) for taxane-based, CMF, and other chemotherapy, respectively. Our findings showed that adjuvant chemotherapy was associated with increased risk of AKI in elderly women diagnosed with early-stage breast cancer. The risk seemed to vary by regimen type, but the differences were not statistically significant.

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

PubMed

Skedgel, Chris; Rayson, Daniel; Younis, Tallal

2016-01-01

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01).

PubMed

Hagiwara, Yasuhiro; Ohashi, Yasuo; Uesaka, Katsuhiko; Boku, Narikazu; Fukutomi, Akira; Okamura, Yukiyasu; Konishi, Masaru; Matsumoto, Ippei; Kaneoka, Yuji; Shimizu, Yasuhiro; Nakamori, Shoji; Sakamoto, Hirohiko; Morinaga, Soichiro; Kainuma, Osamu; Imai, Koji; Sata, Naohiro; Hishinuma, Shoichi; Ojima, Hitoshi; Yamaguchi, Ryuzo; Hirano, Satoshi; Sudo, Takeshi

2018-04-01

Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial. Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m 2 weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles). HRQOL was assessed using the EuroQol-5D-3L (EQ-5D) questionnaire at baseline, months three and six, and every 6 months thereafter. HRQOL end-points included change in EQ-5D index from baseline, responses to five items in the EQ-5D, and quality-adjusted life months up to 24 months. Of randomised 385 patients, 354 patients were included in HRQOL analysis. Mean change in the EQ-5D index was similar in the S-1 and gemcitabine groups within 6 months from treatment initiation (difference, 0.024; P = 0.112), whereas corresponding mean from 12 to 24 months was better in the S-1 group than in the gemcitabine group (difference, 0.071; P < 0.001). Problems in mobility and pain/discomfort were also less frequent in the S-1 group than in the gemcitabine group in that period. Quality-adjusted life months were longer in the S-1 group than in the gemcitabine group (P < 0.001). Adjuvant chemotherapy with S-1 does not improve HRQOL within 6 months from treatment initiation but does improve HRQOL thereafter and quality-adjusted life months. UMIN000000655 at UMIN CTR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Current Status of Adjuvant Therapy for Colon Cancer

PubMed Central

André, Thierry; Afchain, Pauline; Barrier, Alain; Blanchard, Pierre; Larsen, Annette K.; Tournigand, Christophe; Louvet, Christophe; de Gramont, Aimery

2007-01-01

Due to its frequency and persistently high mortality, colorectal cancer represents a major public health problem. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment, including refinement of ability to predict disease course and response to chemotherapy. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid (FA). Oral fluoropyrimidines (eg, capecitabine, UFT + FA) now offer an alternative to intravenous 5-FU. Adjuvant chemotherapy for stage II colorectal cancer is more controversial. Use of adjuvant chemotherapy does not appear to be justified in patients with no particular risk factors (T3N0 with no poor prognosis factor). In contrast, the risk:benefit ratio in patients with one or more poor prognostic factors (T4 tumor, occlusion or perforation, poorly differentiated tumor, vascular invasion, or < 10 lymph nodes examined) appears to favor adjuvant treatment with FOLFOX4. Ongoing adjuvant trials are evaluating bevacizumab and cetuximab combined with 5-FU and oxaliplatin, and are examining the utility of such potential predictive markers as tumor microsatellite instability and loss of heterozygosity. Duration of therapy and prevention of oxaliplatin neurotoxicity are other critical areas for future research. PMID:19262714

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol

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 totalmore » 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.« less

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

PubMed

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

To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. 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. 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). 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. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of age on survival benefit of adjuvant chemotherapy in elderly patients with Stage III colon cancer.

PubMed

Zuckerman, Ilene H; Rapp, Thomas; Onukwugha, Ebere; Davidoff, Amy; Choti, Michael A; Gardner, James; Seal, Brian; Mullins, C Daniel

2009-08-01

To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer. Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score-matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions. Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used. Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship. The outcome was colon cancer-specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery. All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups. These findings have important clinical and policy implications for the risk-benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.

Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy

PubMed Central

Kriege, M; Hollestelle, A; Jager, A; Huijts, P E A; Berns, E M; Sieuwerts, A M; Meijer-van Gelder, M E; Collée, J M; Devilee, P; Hooning, M J; Martens, J W M; Seynaeve, C

2014-01-01

Background: We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. Methods: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. Results: The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59–6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79–3.93) and 2.05 (1.41–2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. Conclusions: The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients. PMID:24918820

Patterns of adjuvant chemotherapy for stage II and III colon cancer in France and Italy.

PubMed

Bouvier, Anne-Marie; Minicozzi, Pamela; Grosclaude, Pascale; Bouvier, Véronique; Faivre, Jean; Sant, Milena

2013-08-01

European guidelines recommend adjuvant chemotherapy for stage III colon cancer but not for stage II. To determine the extent to which adjuvant chemotherapy was used in Italy and France. A common retrospective database of 2186 colon cancers diagnosed between 2003 and 2005 was analysed according to age, stage and presenting features. 38.9% of patients with stage II and 64.6% with stage III received chemotherapy in Italy, 21.7% and 65.1% in France. For stage II, the association between country and chemotherapy was only significant in patients diagnosed out of emergency (ORItaly/France: 3.05 [2.12-4.37], p<0.001) whereas patients diagnosed in emergency were as likely to receive chemotherapy in both countries. For stage III, there was a trend to a higher administration of chemotherapy for elderly patients in France compared to Italy. French patients were more likely than Italian to receive chemotherapy (OR: 1.91[1.32-2.78], p=0.001). Chemotherapy for stage III colon cancer was as extensively used in Italy as in France for young patients. Its administration could be increased in patients over 75. Stage II patients with a lower risk of relapse received chemotherapy more often in Italy than in France. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

PubMed

Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

2009-05-16

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

PubMed

Feng, Siyang; Wang, Yuanyuan; Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

2015-01-01

the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. ClinicalTrials.gov NCT02430974.

Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer

PubMed Central

Sanoff, Hanna K.; Carpenter, William R.; Martin, Christopher F.; Sargent, Daniel J.; Meyerhardt, Jeffrey A.; Stürmer, Til; Fine, Jason P.; Weeks, Jane; Niland, Joyce; Kahn, Katherine L.; Schymura, Maria J.

2012-01-01

Background The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain. Subjects and Methods Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources—the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER–Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non–oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004–2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan–Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided. Results The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER–Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR–Medicaid, 82% [n = 54]; NYSCR–Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER–Medicare, and in the NYSCR–Medicare cohort (non–oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy

Impact of Oncotype DX breast Recurrence Score testing on adjuvant chemotherapy use in early breast cancer: Real world experience in Greater Manchester, UK.

PubMed

Loncaster, J; Armstrong, A; Howell, S; Wilson, G; Welch, R; Chittalia, A; Valentine, W J; Bundred, N J

2017-05-01

The National Institute for Health and Clinical Excellence (NICE) recommended the Oncotype DX ® Breast Recurrence Score ® (RS) assay as an option for informing adjuvant chemotherapy decisions in node-negative, oestrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer assessed to be at intermediate risk of recurrence based on clinicopathological factors. We evaluated the impact of RS testing on adjuvant chemotherapy decision-making in routine clinical practice in a UK Cancer Network. RS testing was performed in 201 females with newly diagnosed, ER+, HER2-negative, invasive breast cancer who underwent breast surgery with curative intent, were calculated to have a >3% overall survival benefit at 10 years from adjuvant chemotherapy based on PREDICT, and were considered for adjuvant chemotherapy. The impact of RS testing on adjuvant treatment decisions/associated cost was assessed. In all patients, the multi-disciplinary team recommended chemotherapy but the RS result allowed 127/201 patients (63.2%) to avoid unnecessary adjuvant chemotherapy. Amongst ER+, HER2-negative, node-negative patients (eligible for Oncotype DX testing in UK guidelines), 60.3% were spared chemotherapy. In node-positive patients, the assay reduced the use of chemotherapy by 69.2%. The use of RS testing to guide treatment in these 201 patients was associated with significant cost saving (when considering the cost of RS testing for all patients plus chemotherapy and its associated cost for 74 patients). Incorporating RS testing into routine clinical practice for selected node-negative and node-positive breast cancer patients significantly reduces the use of chemotherapy (p < 0.001) with its associated morbidity and costs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study.

PubMed

Sgouros, Joseph; Aravantinos, Gerasimos; Kouvatseas, George; Rapti, Anna; Stamoulis, George; Bisvikis, Anastasios; Res, Helen; Samantas, Epameinondas

2015-12-01

Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient's preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS). We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach. Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients. In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed.

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan.

PubMed

Urushiyama, Hirokazu; Jo, Taisuke; Yasunaga, Hideo; Yamauchi, Yasuhiro; Matsui, Hiroki; Hasegawa, Wakae; Takeshima, Hideyuki; Hiraishi, Yoshihisa; Mitani, Akihisa; Fushimi, Kiyohide; Nagase, Takahide

2017-09-02

The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis. Median recurrence-free survival was 1146 days (95% confidence interval [CI], 885-1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464-1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91-1.84). There was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue.

Adjuvant chemotherapy in elderly women with breast cancer: patients' perspectives on information giving and decision making.

PubMed

Harder, Helena; Ballinger, Rachel; Langridge, Carolyn; Ring, Alistair; Fallowfield, Lesley J

2013-12-01

Decisions about adjuvant chemotherapy in older women with early stage breast cancer (EBC) are often challenging. Uncertainty about benefits due to limited data about treatment efficacy and outcomes complicates decision making. This qualitative study explored older patients' experiences and preferences towards information giving and ultimate decisions about adjuvant chemotherapy. Clinicians from 24 UK breast cancer teams reported on adjuvant chemotherapy decisions for women aged ≥70 years with EBC from April 2010 to December 2011. Women who were offered chemotherapy were invited to participate in structured interviews. Self-reported quality of life (QoL) and functional ability were assessed. Qualitative methods were used to identify themes associated with information giving and decision making. A total of 58/95 eligible women (61%) participated. Median age was 73 years (range 70-83). Mean total scores for QoL and functional ability were average. The majority of women preferred to make their treatment decisions collaboratively with a clinician (59%) or on their own (19%). The main reasons influencing decisions to accept chemotherapy were categorised as prevention of recurrence and clinician recommendation. Side effects, length of treatment, impact on QoL, low survival benefits and clinician recommendation influenced decisions to decline chemotherapy. The majority (80%) were satisfied with information provision, the communication with their clinician and explanation of treatment. Older women with EBC preferred to be involved in clinical decision making. Clinician recommendation plays a significant role in either accepting or declining chemotherapy. Well-informed decision making and effective communication between clinicians, older women and their family members are therefore important. Copyright © 2013 John Wiley & Sons, Ltd.

The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

PubMed

Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

2018-05-04

The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

Platelet-to-lymphocyte ratio predicts the prognosis of patients with non-small cell lung cancer treated with surgery and postoperative adjuvant chemotherapy.

PubMed

Toda, Michihito; Tsukioka, Takuma; Izumi, Nobuhiro; Komatsu, Hiroaki; Okada, Satoshi; Hara, Kantaro; Miyamoto, Hikaru; Ito, Ryuichi; Shibata, Toshihiko; Nishiyama, Noritoshi

2018-01-01

Markers of preoperative tumor immunity, such as platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors for patients with various cancers. However, the relationship between PLR and the prognosis of non-small cell lung cancer (NSCLC) patients treated with surgery and adjuvant chemotherapy as a multidisciplinary treatment is unknown. We enrolled 327 NSCLC patients treated surgically with or without adjuvant chemotherapy (78 and 249 patients, respectively) at our hospital from 2008 to 2012. Patients had no preoperative hematological disease or infection. Preoperative PLR and clinicopathologic characteristics were recorded and their potential associations and prognostic values were assessed by Kaplan-Meier and multivariate Cox regression. The optimal cut-off value for high and low PLR was calculated from receiver operating characteristic curves. The five-year overall survival rates for patients with low and high PLR were 78% and 57% (P < 0.01) for all patients, and 69% and 37% (P < 0.01) for patients who received adjuvant chemotherapy, respectively. Similarly, the five-year disease-free survival rates for patients with low and high PLR were 66% and 62% (P = 0.03) for all patients, and 47% and 14% (P < 0.01) for patients who received adjuvant chemotherapy, respectively. Cox proportional hazard regression indicated that high PLR was an independent prognostic factor for both overall and disease-free survival in the adjuvant chemotherapy group. Elevated PLR predicts poor prognosis in surgically treated NSCLC patients, especially those who receive adjuvant chemotherapy. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Perez, Edith A.; Suman, Vera J.; Davidson, Nancy E.; Gralow, Julie R.; Kaufman, Peter A.; Visscher, Daniel W.; Chen, Beiyun; Ingle, James N.; Dakhil, Shaker R.; Zujewski, JoAnne; Moreno-Aspitia, Alvaro; Pisansky, Thomas M.; Jenkins, Robert B.

2011-01-01

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen. PMID:22042958

Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4

PubMed Central

Miura, Nami; Kamita, Masahiro; Kakuya, Takanori; Fujiwara, Yutaka; Tsuta, Koji; Shiraishi, Hideaki; Takeshita, Fumitaka; Ochiya, Takahiro; Shoji, Hirokazu; Huang, Wilber; Ohe, Yuichiro; Yamada, Tesshi; Honda, Kazufumi

2016-01-01

Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ). In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.10, which was a clinical trial to probe the clinical benefits of ADJ in stage-IB/II patients with NSCLC. The patients who were enrolled by JBR.10 were classified into 2 subgroups according to expression of the ACTN4 transcript: ACTN4 positive (ACTN4 (+)) and ACTN4 negative (ACTN4 (−)). In the ACTN4 (+) group, overall survival (OS) was significantly higher in the ADJ subgroup compared with the observation subgroup (OBS), indicating a significant survival benefit of ADJ. However, no difference in OS was found between ADJ and OBS groups in ACTN4 (−). Although ACTN4 expression level did not correlate with the chemosensitivity of cancer cell lines for cytotoxic drugs, the metastatic potential of A549 lung adenocarcinoma cells was significantly reduced by ACTN4 shRNA in in vitro assays and in an animal transplantation model. The clinical and preclinical data suggested that ACTN4 is a potential predictive biomarker for efficacy of ADJ in stage-IB/II patients with NSCLC, by reflecting the metastatic potential of tumor cells. PMID:27121206

Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4.

PubMed

Miura, Nami; Kamita, Masahiro; Kakuya, Takanori; Fujiwara, Yutaka; Tsuta, Koji; Shiraishi, Hideaki; Takeshita, Fumitaka; Ochiya, Takahiro; Shoji, Hirokazu; Huang, Wilber; Ohe, Yuichiro; Yamada, Tesshi; Honda, Kazufumi

2016-05-31

Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ).In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.10, which was a clinical trial to probe the clinical benefits of ADJ in stage-IB/II patients with NSCLC. The patients who were enrolled by JBR.10 were classified into 2 subgroups according to expression of the ACTN4 transcript: ACTN4 positive (ACTN4 (+)) and ACTN4 negative (ACTN4 (-)). In the ACTN4 (+) group, overall survival (OS) was significantly higher in the ADJ subgroup compared with the observation subgroup (OBS), indicating a significant survival benefit of ADJ. However, no difference in OS was found between ADJ and OBS groups in ACTN4 (-). Although ACTN4 expression level did not correlate with the chemosensitivity of cancer cell lines for cytotoxic drugs, the metastatic potential of A549 lung adenocarcinoma cells was significantly reduced by ACTN4 shRNA in in vitro assays and in an animal transplantation model. The clinical and preclinical data suggested that ACTN4 is a potential predictive biomarker for efficacy of ADJ in stage-IB/II patients with NSCLC, by reflecting the metastatic potential of tumor cells.

Systemic and Adjuvant Therapies for Intrahepatic Cholangiocarcinoma.

PubMed

Chun, Yun Shin; Javle, Milind

2017-01-01

Intrahepatic cholangiocarcinoma represents the second most common primary liver cancer and is increasing in incidence. Most patients are diagnosed at an advanced, nonsurgical stage and only about 1 in 5 cases are surgically resectable. Despite surgery, the 5-year survival is low at only 30%. Multifocal, node- or margin-positive disease is at a higher risk of recurrence after resection. There is no level 1 evidence in support of postoperative adjuvant therapy. A recent adjuvant therapy phase III trial from the Partenariat de Recherche en Oncologie Digestive-Actions Concertées dans les Cancers Colo-Rectaux et Digestifs (PRODIGE) group reported no survival advantage with adjuvant gemcitabine and oxaliplatin therapy. Locally advanced or metastatic cholangiocarcinoma is treated with gemcitabine-based systemic chemotherapy with suboptimal response and survival. Integration of local therapy such as focal radiation along with induction chemotherapy is now being investigated in multicenter clinical trials. Recent molecular profiling studies have indicated that about 30% to 40% of intrahepatic cholangiocarcinoma cases have actionable mutations. These include fibroblast growth factor receptor (FGFR), isocitrate dehyrogenase 1 (IDH1), epidermal growth factor receptor (EGFR), and BRAF genetic aberrations. Clinical trials targeting these mutations as well as immune therapy using programmed cell death 1 (PD1) inhibitors indicated a promising early signal showing clinical efficacy.

Decreased contralateral breast volume after mastectomy, adjuvant chemotherapy, and anti-estrogen therapy, in particular in breasts with high density.

PubMed

Ishii, Naohiro; Ando, Jiro; Harao, Michiko; Takemae, Masaru; Kishi, Kazuo

2017-10-01

Adjuvant chemotherapy and anti-estrogenic therapy can result in decreased volume of the contralateral breast, following mastectomy for the treatment of breast cancer. However, no data on the effect of adjuvant therapy on contralateral breast volume have previously been reported. We aimed to evaluate the extent to which adjuvant therapy and differences in breast density contribute to decreased breast volume. We conducted a prospective cohort study, selecting 40 nonconsecutive patients who underwent immediate breast reconstruction with mastectomy and expander insertion followed by expander replacement. We measured the contralateral breast volume before each procedure. The extent of the change was analyzed with respect to adjuvant therapy and breast density measured by preoperative mammography. The greatest decrease in breast volume was 135.1 cm 3 . The decrease in breast volume was significantly larger in the adjuvant therapy (+) group, particularly in patients with high breast density, than in the adjuvant therapy (-) group. Significant differences between the chemotherapy (+), tamoxifen (+) group and the chemotherapy (-), tamoxifen (+) group were not found. Breast density scores had a range of 2.0-3.3 (mean: 2.8). In breast reconstruction, particularly when performed in one stage, preoperative mammography findings are valuable to plastic surgeons, and possible decreases in the contralateral breast volume due to adjuvant therapy, particularly in patients with high breast density, should be considered carefully. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Association of Adjuvant Chemotherapy With Survival in Patients With Stage II or III Gastric Cancer

PubMed Central

Jiang, Yuming; Li, Tuanjie; Liang, Xiaoling; Hu, Yanfeng; Huang, Lei; Liao, Zhenchen; Zhao, Liying; Han, Zhen; Zhu, Shuguang; Wang, Menglan; Xu, Yangwei; Qi, Xiaolong; Liu, Hao; Yang, Yang; Yu, Jiang; Liu, Wei; Cai, Shirong

2017-01-01

Importance The current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy. Objective To construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. Design, Setting, and Participants In this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study’s inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016. Main Outcomes and Measures Concordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival. Results Of the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival

Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013.

PubMed

Oseledchyk, A; Leitao, M M; Konner, J; O'Cearbhaill, R E; Zamarin, D; Sonoda, Y; Gardner, G J; Long Roche, K; Aghajanian, C A; Grisham, R N; Brown, C L; Snyder, A; Chi, D S; Soslow, R A; Abu-Rustum, N R; Zivanovic, O

2017-12-01

We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database. The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model. In all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS-81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359-0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage. Adjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Projecting Event-Based Analysis Dates in Clinical Trials: An Illustration Based on the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration. Projecting analysis dates for the IDEA collaboration.

PubMed

Renfro, Lindsay A; Grothey, Axel M; Paul, James; Floriani, Irene; Bonnetain, Franck; Niedzwiecki, Donna; Yamanaka, Takeharu; Souglakos, Ioannis; Yothers, Greg; Sargent, Daniel J

2014-12-01

Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Real-time projection of the final analysis time during a

Projecting Event-Based Analysis Dates in Clinical Trials: An Illustration Based on the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration. Projecting analysis dates for the IDEA collaboration

PubMed Central

Renfro, Lindsay A.; Grothey, Axel M.; Paul, James; Floriani, Irene; Bonnetain, Franck; Niedzwiecki, Donna; Yamanaka, Takeharu; Souglakos, Ioannis; Yothers, Greg; Sargent, Daniel J.

2015-01-01

Purpose Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. Patients and Methods In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Results Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Conclusions Real

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data.

PubMed

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Le Pechoux, Cécile; Michiels, Stefan

2013-06-01

The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. We analysed individual patients' data from 15,071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ(2)=0.83, 95% CI 0.83-0.83 in trials without radiotherapy, and 0.87, 0.87-0.87 in trials with radiotherapy) and excellent at trial level (R(2)=0.92, 95% CI 0.88-0.95 in trials without radiotherapy and 0.99, 0.98-1.00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ(2) range 0.77-0.85, dependent on the regimen being assessed) and trial level (R(2) range 0.89-0.97). In studies with data on locoregional control, individual-level correlations were good (ρ(2)=0.71, 95% CI 0.71-0.71 for concurrent chemotherapy

Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative.

PubMed

Pashankar, Farzana; Hale, Juliet P; Dang, Ha; Krailo, Mark; Brady, William E; Rodriguez-Galindo, Carlos; Nicholson, James C; Murray, Matthew J; Bilmire, Deborah F; Stoneham, Sara; Arul, G Suren; Olson, Thomas A; Stark, Daniel; Shaikh, Furqan; Amatruda, James F; Covens, Allan; Gershenson, David M; Frazier, A Lindsay

2016-01-15

There is a debate regarding the management of ovarian immature teratomas (ITs). In adult women, postoperative chemotherapy is standard except for stage I, grade 1 disease, whereas surgery alone is standard in pediatric patients. To determine the role of chemotherapy, a pooled analysis of pediatric and adult clinical trials was conducted. Data from 7 pediatric trials and 2 adult trials were merged in the Malignant Germ Cell International Collaborative data set. Four trials included patients with newly diagnosed pure ovarian ITs and were selected (Pediatric Oncology Group/Children's Cancer Group Intergroup Study (INT 0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed separately. The primary outcome measures were event-free survival (EFS) and overall survival (OS). One hundred seventy-nine patients were included (98 pediatric patients and 81 adult patients). Ninety pediatric patients were treated with surgery alone, whereas all adult patients received chemotherapy. The 5-year EFS and OS were 91% and 99%, respectively, for the pediatric cohort and 87% and 93%, respectively, for the adults. There were no relapses in grade 1 patients, regardless of the stage or age. Only 1 adult patient with a grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92 (0.72-0.98) for stage I/II and 0.52 (0.22-0.75) for stage III in the pediatric cohort (P = .005) and 0.91 (0.69-0.98) for stage I/II and 0.65 (0.39-0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort. The grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved. Cancer 2016;122:230-237. © 2015 American Cancer Society. © 2015 American Cancer Society.

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…

Tolerance of adjuvant letrozole outside of clinical trials.

PubMed

Fontaine, C; Meulemans, A; Huizing, M; Collen, C; Kaufman, L; De Mey, J; Bourgain, C; Verfaillie, G; Lamote, J; Sacre, R; Schallier, D; Neyns, B; Vermorken, J; De Grève, J

2008-08-01

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.

Effect of prior chemotherapy regimens on the efficacy of endocrine therapy within a German cohort of the TEAM trial.

PubMed

Bossart, Michaela; Hadji, Peyman; Klar, Maximilian; Kieback, Dirk G; Hasenburg, Annette

2014-01-01

Prior chemotherapy may affect the efficacy of endocrine therapy. The tamoxifen exemestane adjuvant multinational (TEAM) trial compared 5 years of adjuvant exemestane with the sequence of tamoxifen followed by exemestane in postmenopausal women with hormone-receptor-positive breast cancer. A total of 1,502 patients were enrolled in Germany (739 received tamoxifen followed by exemestan and 610 exemestan alone). A retrospective analysis of the German cohort of TEAM was conducted to determine whether prior chemotherapy affected clinical outcome of endocrine therapy. Overall survival, disease-free survival and distant recurrence were similar between patients who received sequential therapy and those who received exemestane monotherapy, irrespective of prior chemotherapy. Overall survival was not significantly different between patients who had received prior chemotherapy and those who had not (P = 0.2836). Disease-free survival and distant recurrence were significantly better in patients who had not received prior chemotherapy versus those who had (P = 0.0308 and P = 0.0001). In patients receiving sequential therapy, there were no significant differences in overall survival according to prior chemotherapy use (P = 0.1812). However, disease-free survival and distant recurrence were significantly different dependent on prior chemotherapy (P = 0.0143 and P = 0.0053). In conclusion, there was no difference in overall survival between breast cancer patients who did receive prior chemotherapy before endocrine therapy and those who had not. Patients who had not received prior chemotherapy had significantly improved disease-free survival and less distant recurrence versus those who had received chemotherapy.

Simultaneous detection of circulating immunological parameters and tumor biomarkers in early stage breast cancer patients during adjuvant chemotherapy.

PubMed

Rovati, B; Mariucci, S; Delfanti, S; Grasso, D; Tinelli, C; Torre, C; De Amici, M; Pedrazzoli, P

2016-06-01

Chemotherapy-induced immune suppression has mainly been studied in patients with advanced cancer, but the influence of chemotherapy on the immune system in early stage cancer patients has so far not been studied systematically. The aim of the present study was to monitor the immune system during anthracycline- and taxane-based adjuvant chemotherapy in early stage breast cancer patients, to assess the impact of circulating tumor cells on selected immune parameters and to reveal putative angiogenic effects of circulating endothelial cells. Peripheral blood samples from 20 early stage breast cancer patients were analyzed using a flow cytometric multi-color of antibodies to enumerate lymphocyte and dendritic cell subsets, as well as endothelial and tumor cells. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of various serological factors. During chemotherapy, all immunological parameters and angiogenesis surrogate biomarkers showed significant decreases. The numbers of circulating tumor cells showed significant inverse correlations with the numbers of T helper cells, a lymphocyte subset directly related to effective anti-tumor responses. Reduced T helper cell numbers may contribute to systemic immunosuppression and, as such, the activation of dormant tumor cells. From our results we conclude that adjuvant chemotherapy suppresses immune function in early stage breast cancer patients. In addition, we conclude that the presence of circulating tumor cells, defined as pan-cytokeratin(+), CD326(+), CD45(-) cells, may serve as an important indicator of a patient's immune status. Further investigations are needed to firmly define circulating tumor cells as a predictor for the success of breast cancer adjuvant chemotherapy.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.

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} orallymore » 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.« less

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

PubMed Central

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Pechoux, Cécile Le; Michiels, Stefan

2013-01-01

Summary Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2=0·83, 95% CI 0·83–0·83 in trials without radiotherapy, and 0·87, 0·87–0·87 in trials with radiotherapy) and excellent at trial level (R2=0·92, 95% CI 0·88–0·95 in trials without radiotherapy and 0·99, 0·98–1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77–0·85, dependent on the regimen being assessed) and trial level (R2 range 0·89–0·97). In studies with data on locoregional control, individual-level correlations were good (�

Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

PubMed

van Nes, J G H; Seynaeve, C; Maartense, E; Roumen, R M H; de Jong, R S; Beex, L V A M; Meershoek-Klein Kranenbarg, W M; Putter, H; Nortier, J W R; van de Velde, C J H

2010-05-01

The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

PubMed

Lonardi, S; Sobrero, A; Rosati, G; Di Bartolomeo, M; Ronzoni, M; Aprile, G; Massida, B; Scartozzi, M; Banzi, M; Zampino, M G; Pasini, F; Marchetti, P; Cantore, M; Zaniboni, A; Rimassa, L; Ciuffreda, L; Ferrari, D; Barni, S; Zagonel, V; Maiello, E; Rulli, E; Labianca, R

2016-11-01

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. NCT00646607. © The Author 2016. Published by Oxford University Press on behalf of

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer

PubMed Central

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-01-01

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype. PMID:27340922

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer.

PubMed

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-08-02

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

Effect of YH0618 soup on chemotherapy-induced toxicity in patients with cancer who have completed chemotherapy: study protocol for a randomized controlled trial.

PubMed

You, Jie-Shu; Chen, Jian-Ping; Chan, Jessie S M; Lee, Ho-Fun; Wong, Mei-Kuen; Yeung, Wing-Fai; Lao, Li-Xing

2016-07-26

The incidence of cancer has been staying at a high level worldwide in recent years. With advances in cancer diagnosis and therapy strategy, the survival rate of patients with cancer has been increasing, but the side effects of these treatments, especially chemotherapy, are obvious even when the chemotherapy ceases. YH0618, a prescription, has showed efficacy in reducing chemotherapy-induced toxicity through long clinical practice. However, there is no scientific research exploring the effects of YH0618 in patients with cancer. Therefore, using a randomized controlled trial, this study will explore the efficacy of YH0618 on ameliorating chemotherapy-induced toxicity including dermatologic toxicity, myelosuppression, hepatotoxicity and nephrotoxicity and improving fatigue in cancer patients who have completed chemotherapy. This is a prospective assessor-blinded, parallel, randomized controlled trial. Patients with cancer at any stage who have completed chemotherapy within two weeks will be randomly divided into group A (YH0618) and group B (wait-list) using a 1:1 allocation ratio. The chemotherapeutic agents include taxanes or anthracyclines. Subjects assigned to group A will receive YH0618 soup 6 days a week for 6 weeks and uncontrolled follow-up for 6 weeks, while group B are required to wait for 6 weeks before receiving YH0618 intervention. The primary outcome of this study is the incidence of protocol-specified grade ≥2 dermatologic toxicities graded by NCI CTCAE Chinese version 4.0 and changes of fingernail color, face skin color and tongue color evaluated by the L*a*b system within 6 weeks. There are some secondary outcomes associated with dermatologic toxicity including fatigue and clinical objective examination. There are few scientific and safe methods in ameliorating chemotherapy-induced toxicity. The proposed study may provide direct and convincing evidence to support YH0618 as an adjuvant treatment for reducing chemotherapy-induced toxicity, which

Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials.

PubMed

Alden, Ryan S; Mandrekar, Sumithra J; Oxnard, Geoffrey R

2015-09-01

Genotype-directed targeted therapies have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC) but they have not yet been comprehensively studied in the adjuvant setting. Previous trials of adjuvant targeted therapy in unselected early stage NSCLC patients showed no benefit versus placebo, however retrospective data suggests improved disease free survival (DFS) with epidermal growth factor receptor (EGFR) inhibitors in patients with appropriate molecular alterations. A definitive prospective, randomized, placebo-controlled trial of targeted therapies for NSCLC is needed to determine the efficacy of targeted therapy following surgical resection and standard adjuvant therapy. The principal challenges facing such a trial are (I) identification of actionable alterations in early stage patients; and (II) realization of sufficient enrollment to power definitive analyses. The ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) was designed to overcome these challenges. Using the national clinical trials network (NCTN) of the National Cancer Institute (NCI), several thousand patients with operable NSCLC will undergo tumor genotyping for EGFR mutations or rearrangement of anaplastic lymphoma kinase (ALK). Following resection and completion of standard adjuvant therapy, patients with EGFR-mutant NSCLC will be randomized to erlotinib versus placebo (1:1), those with ALK-rearranged NSCLC will be randomized to crizotinib versus placebo (1:1), while those not enrolled onto the adjuvant trials will continue to be followed on the screening trial. ALCHEMIST also provides for the collection of tissue at baseline and at recurrence (if available) to characterize mechanisms of recurrence and of resistance to targeted therapy. Thus, ALCHEMIST is a platform for validation of targeted therapy as part of curative care in NSCLC and creates an opportunity to advance our understanding of disease biology.

Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer.

PubMed

Inoue, Masayoshi; Maeda, Hajime; Takeuchi, Yukiyasu; Fukuhara, Kenjiro; Shintani, Yasushi; Funakoshi, Yasunobu; Funaki, Soichiro; Nojiri, Takashi; Kusu, Takashi; Kusumoto, Hidenori; Kimura, Toru; Okumura, Meinoshin

2018-04-01

We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.

Retrospective study of management of uterine sarcomas at Oxford 1990-1998: role of adjuvant treatment.

PubMed

Riddle, P J; Echeta, C B; Manek, S; Lavery, B A; Charnock, F M L; Mackenzie, I; Ganesan, T S

2002-02-01

We report a retrospective study of 47 consecutive patients with uterine sarcoma treated at the Churchill Hospital in Oxford between 1990-1998. The mainstay of treatment was surgery with adjuvant chemotherapy and radiotherapy reserved for selected patients with early stage disease. Overall 1 and 2 year survival was 49% and 30% respectively compared with 73% and 55% in the group who received adjuvant chemotherapy/radiotherapy. Median survival was 11 months for the group as a whole compared to 32.9 months in the adjuvant therapy group. This is a retrospective review with small numbers and considerable selection bias, however, given the poor survival of patients with this disease, adjuvant treatment should be considered in future trials of patients with uterine sarcoma.

Adjuvant Chemotherapy With FOLFOX for Primary Colorectal Cancer Is Associated With Increased Somatic Gene Mutations and Inferior Survival in Patients Undergoing Hepatectomy for Metachronous Liver Metastases

PubMed Central

Andreou, Andreas; Kopetz, Scott; Maru, Dipen M.; Chen, Su S.; Zimmitti, Giuseppe; Brouquet, Antoine; Shindoh, Junichi; Curley, Steven A.; Garrett, Christopher; Overman, Michael J.; Aloia, Thomas A.; Vauthey, Jean-Nicolas

2013-01-01

Objective We hypothesized that metachronous colorectal liver metastases (CLM) have different biology after failure of oxaliplatin (FOLFOX) compared to 5-fluorouracil (5-FU) or no chemotherapy for adjuvant treatment of colorectal cancer (CRC). Background It is unclear whether patients treated with liver resection for metachronous CLM after adjuvant FOLFOX for CRC have worse outcomes than those who received 5-FU or no chemotherapy. Methods We identified 341 patients who underwent hepatectomy for metachronous CLM (disease-free interval ≥12 months, 1993–2010). Mass-spectroscopy genotyping for somatic gene mutations in CLM was performed in a subset of 129 patients. Results Adjuvant treatment for primary CRC was FOLFOX in 77 patients, 5-FU in 169 patients, and no chemotherapy in 95 patients. Node-positive primary was comparable between FOLFOX and 5-FU but lower in the no-chemotherapy group (P < 0.0001). Median metastasis size was smaller in the FOLFOX group (2.5 cm) than in the 5-FU (3.0 cm) or no-chemotherapy (3.5 cm) groups, (P = 0.008) although prehepatectomy chemotherapy utilization, metastases number, and carcinoembryonic antigen levels were similar. Disease-free survival (DFS) and overall survival (OS) rates after hepatectomy were worse in patients treated with adjuvant FOLFOX [DFS at 3 years: 14% vs 38% (5-FU) vs 45% (no-chemo), OS at 3 years: 58% vs 70% (5-FU) vs 84% (no-chemo)]. On multivariate analysis, adjuvant FOLFOX was associated with worse DFS (P < 0.0001) and OS (P < 0.0001). Mutation analysis revealed ≥1 mutations in 57% of patients (27/47) after FOLFOX, 29% (12/41) after 5-FU, and 32% (13/41) after no chemotherapy (P = 0.011). Conclusions Adjuvant FOLFOX for primary CRC is associated with a high rate of somatic mutations in liver metastases and inferior outcomes after hepatectomy for metachronous CLM. PMID:22968062

Adjuvant chemotherapy with FOLFOX for primary colorectal cancer is associated with increased somatic gene mutations and inferior survival in patients undergoing hepatectomy for metachronous liver metastases.

PubMed

Andreou, Andreas; Kopetz, Scott; Maru, Dipen M; Chen, Su S; Zimmitti, Giuseppe; Brouquet, Antoine; Shindoh, Junichi; Curley, Steven A; Garrett, Christopher; Overman, Michael J; Aloia, Thomas A; Vauthey, Jean-Nicolas

2012-10-01

We hypothesized that metachronous colorectal liver metastases (CLM) have different biology after failure of oxaliplatin (FOLFOX) compared to 5-fluorouracil (5-FU) or no chemotherapy for adjuvant treatment of colorectal cancer (CRC). It is unclear whether patients treated with liver resection for metachronous CLM after adjuvant FOLFOX for CRC have worse outcomes than those who received 5-FU or no chemotherapy. We identified 341 patients who underwent hepatectomy for metachronous CLM (disease-free interval ≥12 months, 1993-2010). Mass-spectroscopy genotyping for somatic gene mutations in CLM was performed in a subset of 129 patients. Adjuvant treatment for primary CRC was FOLFOX in 77 patients, 5-FU in 169 patients, and no chemotherapy in 95 patients. Node-positive primary was comparable between FOLFOX and 5-FU but lower in the no-chemotherapy group (P < 0.0001). Median metastasis size was smaller in the FOLFOX group (2.5 cm) than in the 5-FU (3.0 cm) or no-chemotherapy (3.5 cm) groups, (P = 0.008) although prehepatectomy chemotherapy utilization, metastases number, and carcinoembryonic antigen levels were similar. Disease-free survival (DFS) and overall survival (OS) rates after hepatectomy were worse in patients treated with adjuvant FOLFOX [DFS at 3 years: 14% vs 38% (5-FU) vs 45% (no-chemo), OS at 3 years: 58% vs 70% (5-FU) vs 84% (no-chemo)]. On multivariate analysis, adjuvant FOLFOX was associated with worse DFS (P < 0.0001) and OS (P < 0.0001). Mutation analysis revealed ≥1 mutations in 57% of patients (27/47) after FOLFOX, 29% (12/41) after 5-FU, and 32% (13/41) after no chemotherapy (P = 0.011). Adjuvant FOLFOX for primary CRC is associated with a high rate of somatic mutations in liver metastases and inferior outcomes after hepatectomy for metachronous CLM.

Clinical and economic outcomes associated with adjuvant chemotherapy in elderly patients with early stage operable breast cancer.

PubMed

Sail, Kavita R; Franzini, Luisa; Lairson, David R; Du, Xianglin L

2012-01-01

Breast cancer poses a huge medical burden to the U.S. health-care system, and chemotherapy is an important contributor to cancer costs. This article examines the differences between breast cancer patients who received chemotherapy and those who did not in costs and survival by age, treatment, and axillary node status. We studied a cohort of 23,110 node-positive and 31,572 node-negative women aged 65 years and older diagnosed with incident American Joint Committee on Cancer stage I, II, or IIIA breast cancer between January 1, 1991, and December 31, 2002, using Surveillance Epidemiology and End Results-Medicare data. Total treatment costs and costs associated with the use of chemotherapy were estimated by using the phase-of-care approach. The phase-specific costs were combined to estimate total Medicare payments for cancer care from diagnosis to death. Cox proportional hazard ratio of mortality was used to determine the effectiveness of adjuvant chemotherapy after adjusting for selected patient and tumor characteristics. We used propensity scores to minimize the bias associated with the receipt of adjuvant chemotherapy. Regression-adjusted difference in the average lifetime cost estimates for all node-positive patients receiving chemotherapy was approximately $2438 and was significantly higher (P < 0.05) than for patients not receiving chemotherapy. Mortality was significantly lower in node-positive and node-negative women aged 65 to 74 years receiving chemotherapy. Decision makers can use cost and effectiveness estimates from this study to assess the relative value of chemotherapy in different age groups. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

PubMed

Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0

Correlation study between osteoporosis and hematopoiesis in the context of adjuvant chemotherapy for breast cancer.

PubMed

Schyrr, Frédérica; Wolfer, Anita; Pasquier, Jérôme; Nicoulaz, Anne-Laure; Lamy, Olivier; Naveiras, Olaia

2018-02-01

This retrospective study attempts to establish if a correlation exists between osteoporosis and hematopoiesis before and after adjuvant chemotherapy in the context of non-metastatic breast cancer. Osteoporosis is interpreted both as a direct marker of osteoblastic decline and as an indirect marker of increased bone marrow adiposity within the hematopoietic microenvironment. Patients from the "Centre du Sein" at CHUV (Centre Hospitalier Universitaire Vaudois) undergoing adjuvant chemotherapy were included in this study. Evolution of blood counts was studied in correlation with the osteoporosis status. Toxicity of chemotherapy was coded according to published probability of febrile neutropenia. One hundred forty-three women were included: mean age 52.1 ± 12.5 years, mean BMI (body mass index) 24.4 ± 4.1. BMD (bone mineral density) scored osteoporotic in 32% and osteopenic in 45%. Prior to chemotherapy, BMD was positively correlated with neutrophil (p < 0.001) and thrombocyte (p = 0.01) count; TBS (trabecular bone score) was not correlated with blood count. After the first cycle of chemotherapy, an increase of one point in TBS correlated with a decrease of 57% on the time to reach leucocyte nadir (p = 0.004). There was a positive correlation between BMD and risk of infection (p < 0.001). Our data demonstrates an association between osteoporosis and lower blood counts in a younger cohort than previously published, extending it for the first time to neutrophil counts in females. Our results suggest that the healthier the bone, the earlier the lowest leucocyte count value, prompting further research on this area.

Cost-utility analysis of the newly recommended adjuvant chemotherapy for resectable gastric cancer patients in the 2011 Chinese National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Gastric Cancer.

PubMed

Chongqing, Tan; Liubao, Peng; Xiaohui, Zeng; Jianhe, Li; Xiaomin, Wan; Gannong, Chen; Siying, Wang; Lihui, Ouyang; Ziying, Zhao

2014-03-01

Postoperative adjuvant chemotherapy with capecitabine and oxaliplatin was first recommended for resectable gastric cancer patients in the 2011 Chinese National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Gastric Cancer, but the economic influence of this therapy in China is unknown. The aim of the present study was to determine the cost-effectiveness of adjuvant chemotherapy with capecitabine and oxaliplatin after a gastrectomy with extended (D2) lymph-node dissection, compared with a D2 gastrectomy alone, for patients with stage II-IIIB gastric cancer. On the basis of data from the CLASSIC trial, a Markov model was created to determine economic and clinical data for patients in the chemotherapy and surgery group (CSG) and the surgery-only group (SOG). The costs, presented in 2010 US dollars and estimated from the perspective of the Chinese health-care system, were obtained from the published literature and the local health system. The utilities were based on published literature. Costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were estimated. A lifetime horizon and a 3 % annual discount rate were used. One-way and probabilistic sensitivity analyses were performed. For the base case, the CSG compared with SOG would increase LYs and QALYs in a 3-, 5-, 10- or 30-year time horizon (except the QALYs at 3 or 5 years). In the short run (such as in 3 or 5 years), the medical costs would increase owing to adjuvant chemotherapy of capecitabine plus oxaliplatin after D2 gastrectomy, but in the long run the costs would decline. The ICERs suggested that the SOG was dominant at 3 or 5 years and the CSG was dominant at 10 or 30 years. The one-way sensitivity analysis showed that the utility of disease-free survival for 1-10 years for the SOG and the cost of oxaliplatin were the most influential parameters. The probabilistic sensitivity analysis predicted a 98.6 % likelihood that the ICER

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

Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

PubMed

Chen, Bihong T; Sethi, Sean K; Jin, Taihao; Patel, Sunita K; Ye, Ningrong; Sun, Can-Lan; Rockne, Russell C; Haacke, E Mark; Root, James C; Saykin, Andrew J; Ahles, Tim A; Holodny, Andrei I; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Somlo, George; Li, Daneng; Yang, Richard; Tan, Heidi; Katheria, Vani; Morrison, Rachel; Hurria, Arti

2018-05-02

Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for

[Two Cases of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

PubMed

Ozawa, Michinobu; Kuromoto, Akito; Morozumi, Kento; Satou, Masahiko; Hoshi, Senji; Numahata, Kenji

2017-10-01

Case 1 : A 48-year-old man presenting with gross hematuria was suspected to have a tumor located in the bladder dome. He was referred to our department for further examination and treatment. Cystoscopy showed a dome-shaped mass in the supravesical region. Computed tomography and magnetic resonance imaging indicated the possibility of urachal carcinoma and peritoneal dissemination. Therefore, partial cystectomy with urachal resection was performed. The intraoperative findings were disseminated peritoneal nodules and mucus entering the peritoneal cavity from the tumor. On pathological examination, the tumor was classified as a mucinous-type adenocarcinoma, and 6 courses of TS-1/cisplatin (CDDP) therapy were administered to the patient as adjuvant chemotherapy. To date (10 months since the surgery), there has been no disease progression. Case 2 : A 76-year-old woman was referred to our department with a finding of a tumor in the bladder dome during her detailed examination for lung tumors. Cystoscopy showed nodular tumors, indicating lung metastases of the urachal carcinoma. Therefore, partial cystectomy with urachal resection was performed. On pathological examination, the tumor was classified as an enteric-type adenocarcinoma, and 2 courses of TS-1/CDDP therapy were administered to the patient as adjuvant chemotherapy. However, due to the development of marked bone marrow depression, the drugs had to be discontinued. Nonetheless, the lung metastases markedly diminished in size. To date (9 months since the discontinuation of chemotherapy), there has been no disease progression.

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

PubMed Central

Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

2016-01-01

Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

PubMed

Gaß, Paul; Fasching, Peter A; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y; Beckmann, Matthias W; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R

2016-10-01

Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Effect of an exercise training intervention with resistance bands on blood cell counts during chemotherapy for lung cancer: a pilot randomized controlled trial.

PubMed

Karvinen, Kristina H; Esposito, David; Raedeke, Thomas D; Vick, Joshua; Walker, Paul R

2014-01-01

Chemotherapy for lung cancer can have a detrimental effect on white blood cell (WBC) and red blood cell (RBC) counts. Physical exercise may have a role in improving WBCs and RBCs, although few studies have examined cancer patients receiving adjuvant therapies. The purpose of this pilot trial was to examine the effects of an exercise intervention utilizing resistance bands on WBCs and RBCs in lung cancer patients receiving curative intent chemotherapy. A sample of lung cancer patients scheduled for curative intent chemotherapy was randomly assigned to the exercise intervention (EX) condition or usual care (UC) condition. The EX condition participated in a three times weekly exercise program using resistance bands for the duration of chemotherapy. A total of 14 lung cancer patients completed the trial. EX condition participants completed 79% of planned exercise sessions. The EX condition was able to maintain WBCs over the course of the intervention compared to declines in the UC condition (p = .008; d = 1.68). There were no significant differences in change scores in RBCs. Exercise with resistance bands may help attenuate declines in WBCs in lung cancer patients receiving curative intent chemotherapy. Larger trials are warranted to validate these findings. Ultimately these findings could be informative for the development of supportive care strategies for lung cancer patients receiving chemotherapy. Clinical Trials Registration #: NCT01130714.

[Pneumocystis Pneumonia during Adjuvant Chemotherapy for Advanced Colon Cancer - A Case Report].

PubMed

Fujiwara, Yushi; Lee, Shigeru; Kishida, Satoru; Hashiba, Ryoya; Gyobu, Ken; Osugi, Harushi

2015-11-01

We report a case of pneumocystis pneumonia (PCP) during adjuvant chemotherapy for advanced sigmoid colon cancer. A 70-year-old Japanese man was referred to our hospital after complaining of bloody stools. He was diagnosed with advanced sigmoid colon cancer, T2N2aM1b, Stage IV B. After 3 cycles of mFOLFOX6 plus panitumumab as first-line chemotherapy, he received FOLFIRI plus bevacizumab as second-line chemotherapy because of progressive disease. Aprepitant and steroids were administered as antiemetic agents for a short period during each chemotherapy session. During the 2 cycle of FOLFIRI plus bevacizumab, he developed a high fever without respiratory symptoms. Chest CT revealed ground-glass opacities in both the lungs. We first treated him with antibiotics (PIPC/TAZ plus GRNX), suspecting bacterial pneumonia. However, based on the elevation of serum b -D-glucan (148 pg/mL), we diagnosed PCP and initiated SMX/TMP in addition to PIPC/TAZ. The inflammation promptly decreased, and follow-up chest CT revealed the disappearance of the ground-glass opacities. If a patient develops a fever or respiratory symptoms during a course of chemotherapy, we should consider the possibility of PCP and perform careful examinations.

Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer.

PubMed

Lumachi, Franco; Chiara, Giordano B; Foltran, Luisa; Basso, Stefano M M

2015-01-01

Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low-risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high-risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online.

PubMed

Jahn, Beate; Rochau, Ursula; Kurzthaler, Christina; Hubalek, Michael; Miksad, Rebecca; Sroczynski, Gaby; Paulden, Mike; Bundo, Marvin; Stenehjem, David; Brixner, Diana; Krahn, Murray; Siebert, Uwe

2017-10-16

Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer.

PubMed

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Lee, Jung-Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1-3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC.

Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2–3 nasopharyngeal cancer: a multicenter trial of the Forum for Nuclear Cooperation in Asia

PubMed Central

Ohno, Tatsuya; Thinh, Dang Huy Quoc; Kato, Shingo; Devi, C.R. Beena; Tung, Ngo Thanh; Thephamongkhol, Kullathorn; Calaguas, Miriam Joy C.; Zhou, Juying; Chansilpa, Yaowalak; Supriana, Nana; Erawati, Dyah; Banu, Parvin Akhter; Koo, Cho Chul; Kobayashi, Kunihiko; Nakano, Takashi; Tsujii, Hirohiko

2013-01-01

The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2–3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1–4 N2–3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m 2), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m2 on Day 1) and fluorouracil (800 mg/m2 on Days 1–5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3–4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities. PMID:23192700

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

Glutathione S-transferase Pi expression predicts response to adjuvant chemotherapy for stage C colon cancer: a matched historical control study.

PubMed

Jankova, Lucy; Robertson, Graham; Chan, Charles; Tan, King L; Kohonen-Corish, Maija; Fung, Caroline L-S; Clarke, Candice; Lin, Betty P C; Molloy, Mark; Chapuis, Pierre H; Bokey, Les; Dent, Owen F; Clarke, Stephen J

2012-05-28

This study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy. Patients were drawn from a hospital registry of colorectal cancer resections. Those receiving chemotherapy after it was introduced in 1992 were compared with an age and sex matched control group from the preceding period. GST Pi expression was assessed by immunohistochemistry. Overall survival was analysed by the Kaplan-Meier method and Cox regression. From an initial 104 patients treated with chemotherapy and 104 matched controls, 26 were excluded because of non-informative immunohistochemistry, leaving 95 in the treated group and 87 controls. Survival did not differ significantly among patients with low GST Pi who did or did not receive chemotherapy and those with high GST Pi who received chemotherapy (lowest pair-wise p = 0.11) whereas patients with high GST Pi who did not receive chemotherapy experienced markedly poorer survival than any of the other three groups (all pair-wise p <0.01). This result was unaffected by GST Pi genotype. Stage C colon cancer patients with low GST Pi did not benefit from 5-fluourouracil-based adjuvant chemotherapy whereas those with high GST Pi did.

Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients.

PubMed

Fonia, Athina; Cota, Carlo; Setterfield, Jane F; Goldberg, Lynne J; Fenton, David A; Stefanato, Catherine M

2017-05-01

Anagen effluvium with reversible scalp alopecia is a known side effect of chemotherapy. However, there are an increasing number of reports in the literature documenting permanent alopecia in patients treated with taxanes. We sought to describe the clinicopathologic features in breast cancer patients who underwent treatment with taxanes and adjuvant hormonal chemotherapy. We reviewed the clinical and histopathologic information of a cohort of 10 patients treated with taxanes and adjuvant hormonal chemotherapy. We have observed 3 types of clinical patterns of alopecia (types A, B, and C), and have validated the histopathologic features showing alopecia areata-like and female pattern hair loss. The study was based on a small sample size and retrospective retrieval of clinical information and histopathologic review of posttreatment slides. We hypothesize a clinicopathologic model of hair follicle cycle disruption in response to the chemoinflammatory and hormonal insults to the hair follicles resulting in permanent alopecia. Clinicopathologic correlation is paramount to the understanding of the morphobiologic pathways in chemotherapy-induced alopecia caused by taxanes and adjuvant hormonal treatment. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

Aquaporin 1 expression is associated with response to adjuvant chemotherapy in stage II and III colorectal cancer.

PubMed

Imaizumi, Hideko; Ishibashi, Keiichiro; Takenoshita, Seiichi; Ishida, Hideyuki

2018-05-01

Aquaporin 1 (AQP1), which functions as a water transporter, is associated with cancer cell proliferation, invasion, metastasis and angiogenesis in numerous types of solid cancer, including colorectal cancer (CRC). The focus of the present study was to address the potential clinical use of AQP1 expression in CRC as a prognostic and predictive biomarker for disease recurrence and therapeutic outcomes. The current study investigated the expression of AQP1 in surgically resected specimens from 268 patients with stage 0-IV CRC. AQP1 expression was positive in 112 (41.8%) patients, and was significantly associated with left-sided tumors (P<0.01) and with aggressive tumor phenotypes, including depth of invasion (P=0.03), lymph node metastasis (P=0.03), lymphatic invasion (P<0.01) and venous invasion (P<0.01). However, AQP1 expression had no significant prognostic effect on disease-free survival (DFS) in patients with stage II and III CRC following curative surgery. In 84 stage II and III patients who were administered 5-fluorouracil-based adjuvant chemotherapy, positive AQP1 expression was associated with an increased DFS rate compared with that of AQP1-negative patients (P=0.05). Additionally, these results identified that receiving adjuvant chemotherapy was not beneficial to patients with AQP1-negative tumors. This suggests that the expression of AQP1 may be a candidate biomarker predictive of response to 5-fluorouracil-based adjuvant chemotherapy following surgery in patients with stage II and III CRC.

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

Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients.

PubMed

Tsuchiya, Takashi; Honda, Hiroshi; Oikawa, Masaya; Kakita, Tetsuya; Oyama, Atsushi; Oishi, Hidekazu; Tochikubo, Katsuyuki; Hashimoto, Takanao; Kurihara, Shigekazu; Shibakusa, Tetsuro; Kayahara, Takashi

2016-12-01

Nutritional therapy is used to reduce the adverse events (AEs) of anticancer drugs. Here, we determined whether the amino acids cystine and theanine, which provide substrates for glutathione, attenuated the AEs of S-1 adjuvant chemotherapy. Patients scheduled to receive S-1 adjuvant chemotherapy were randomized to the C/T or the control groups. The C/T group received 700 mg cystine and 280 mg theanine orally 1 week before the administration of S-1, which then continued for 5 weeks. Each group received S-1 for 4 weeks. Blood sampling was performed and AEs were evaluated (CTCAE ver. 4.0) before and after the administration of S-1. S-1 was discontinued when AEs ≥ grade 2 occurred. The incidences of AEs of any grade and those over grade 2 were lower in the C/T group than in the controls. The incidence of diarrhea (G ≥ 2) was significantly less (p < 0.05) in the C/T group (3.1 %) than in the controls (25.8 %). The duration and completion rate of the S-1 adjuvant chemotherapy were significantly longer (p < 0.01) and higher (p < 0.01), respectively, in the C/T group (complete ratio: 75.0 %, duration: 24.8 ± 5.8 days) than in the controls (complete ratio: 35.5 %, duration: 20.0 ± 7.7 days). The oral administration of cystine and theanine attenuated the AEs of S-1 adjuvant chemotherapy and increased the S-1 completion rate, suggesting that cystine and theanine is a useful supportive care for chemotherapy.

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer

PubMed Central

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

Background There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. Methods We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Results Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1–3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). Conclusion IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC. PMID:28873393

Evaluation of 5-fluorouracil metabolic enzymes as predictors of response to adjuvant chemotherapy outcomes in patients with stage II/III colorectal cancer: a decision-curve analysis.

PubMed

Shigeta, Kohei; Ishii, Yoshiyuki; Hasegawa, Hirotoshi; Okabayashi, Koji; Kitagawa, Yuko

2014-12-01

The effectiveness of 5-fluorouracil (5-FU)-based adjuvant chemotherapy is reported in patients with colorectal cancer (CRC), but the usefulness of 5-FU metabolic enzymes as predictive biomarkers of the efficacy of this chemotherapy remains unclear. This study aims to verify whether 5-FU metabolic enzymes are predictive biomarkers in the clinical setting of adjuvant chemotherapy for stage II/III CRC. In total, 179 patients with stage II/III CRC who were treated at our institute between 2000 and 2010 were enrolled. Messenger RNA (mRNA) expression of major 5-FU metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase (TP), orotate phosphoribosyl transferase, and β-actin (control) was evaluated using the Danenberg Tumor Profile method. mRNA expression and other clinicopathological data were investigated with regard to CRC relapse. A total of 78 patients underwent surgery alone, while 101 underwent adjuvant chemotherapy (5-FU plus leucovorin [LV] or tegafur plus uracil /LV) following surgery. Relapse-free survival was longer and risk of recurrence was lower in association with high TP mRNA expression than in association with low TP mRNA expression in the adjuvant chemotherapy group (hazard ratio 0.66; 95 % confidence interval 0.47-0.92; p = 0.016), but not in the surgery alone group. mRNA expression of no other enzymes was associated with relapse in both groups. In decision-curve analyses, the predictive efficiency of TP mRNA expression plus clinicopathological factors was slightly better than that of clinicopathological factors only. TP mRNA expression in tumors predicted the effects of adjuvant chemotherapy for stage II/III CRC, although the beneficial effects were marginal.

Glutathione S-transferase Pi expression predicts response to adjuvant chemotherapy for stage C colon cancer: a matched historical control study

PubMed Central

2012-01-01

Background This study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy. Methods Patients were drawn from a hospital registry of colorectal cancer resections. Those receiving chemotherapy after it was introduced in 1992 were compared with an age and sex matched control group from the preceding period. GST Pi expression was assessed by immunohistochemistry. Overall survival was analysed by the Kaplan-Meier method and Cox regression. Results From an initial 104 patients treated with chemotherapy and 104 matched controls, 26 were excluded because of non-informative immunohistochemistry, leaving 95 in the treated group and 87 controls. Survival did not differ significantly among patients with low GST Pi who did or did not receive chemotherapy and those with high GST Pi who received chemotherapy (lowest pair-wise p = 0.11) whereas patients with high GST Pi who did not receive chemotherapy experienced markedly poorer survival than any of the other three groups (all pair-wise p <0.01). This result was unaffected by GST Pi genotype. Conclusion Stage C colon cancer patients with low GST Pi did not benefit from 5-fluourouracil-based adjuvant chemotherapy whereas those with high GST Pi did. PMID:22639861

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

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

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

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

2013-09-10

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. 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. 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). 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.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

PubMed

Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

2015-08-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new

PubMed Central

Boyle, John; Czito, Brian; Willett, Christopher

2015-01-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID:26261730

Adjuvant chemotherapy with sequential cytokine-induced killer (CIK) cells in stage IB non-small cell lung cancer.

PubMed

Li, Da-Peng; Li, Wei; Feng, Jun; Chen, Kai; Tao, Min

2015-01-01

For non-small cell lung cancer (NSCLC) patients at stage IB, adjuvant chemotherapy does not improve survival. Evidence suggests that dendritic cell (DC)-activated cytokine-induced killer (DC-CIK) cell therapy in addition to chemotherapy improves survival for stage I-IIIA NSCLC patients after surgery, but there are not enough data to confirm this benefit specifically for those at stage IB. Herein, we retrospectively evaluated the efficacy and safety of this therapy administered to stage IB NSCLC patients. Sixty-six patients were treated with four-cycle adjuvant chemotherapy initiated 3 weeks after surgical resection. In addition, 28 of these patients underwent DC-CIK therapy on a trimonthly basis (average 3.1 times, range 1-6) beginning 1 month after chemotherapy. The disease-free survival (DFS) rates of the two groups were statistically similar, although patients who received DC-CIK therapy showed slightly higher 1- and 2-year DFS rates (100.0% and 96.4%, respectively, compared with 81.6% and 76.3%). More importantly, patients in the DC-CIK therapy group had significantly longer overall survival (p=0.018). For patients who received treatment after recurrence, the DC-CIK therapy group had longer progression-free survival compared with the chemotherapy-only group. In addition, patients given DC-CIK therapy experienced less fatigue and appetite loss. The rate of adverse side effects was similar between the two groups. In conclusion, for these stage IB NSCLC patients, DC-CIK therapy significantly improved 2-year DFS rates compared with those who received chemotherapy only. DC-CIK therapy also benefited patients' quality of life, and adverse events were acceptable.

Relationship between Topoisomerase 2A RNA Expression and Recurrence after Adjuvant Chemotherapy for Breast Cancer.

PubMed

Sparano, Joseph A; Goldstein, Lori J; Childs, Barrett H; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Sledge, George W; Gray, Robert

2009-12-15

PURPOSE: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. EXPERIMENTAL DESIGN: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. RESULTS: TOP2A expression exhibited the strongest association with increased recurrence risk (P = 0.01), and was significantly associated with recurrence (P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was <18, and a 2.0-fold increase (95% confidence interval, 1.2-3.2, P = 0.003) if there was an intermediate RS of 18 to 30. CONCLUSIONS: In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines, which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker. (Clin Cancer Res 2009;15(24):7693-700).

Time to Adjuvant Chemotherapy for Breast Cancer in National Comprehensive Cancer Network Institutions

PubMed Central

2013-01-01

Background High-quality care must be not only appropriate but also timely. We assessed time to initiation of adjuvant chemotherapy for breast cancer as well as factors associated with delay to help identify targets for future efforts to reduce unnecessary delays. Methods Using data from the National Comprehensive Cancer Network (NCCN) Outcomes Database, we assessed the time from pathological diagnosis to initiation of chemotherapy (TTC) among 6622 women with stage I to stage III breast cancer diagnosed from 2003 through 2009 and treated with adjuvant chemotherapy in nine NCCN centers. Multivariable models were constructed to examine factors associated with TTC. All statistical tests were two-sided. Results Mean TTC was 12.0 weeks overall and increased over the study period. A number of factors were associated with a longer TTC. The largest effects were associated with therapeutic factors, including immediate postmastectomy reconstruction (2.7 weeks; P < .001), re-excision (2.1 weeks; P < .001), and use of the 21-gene reverse-transcription polymerase chain reaction assay (2.2 weeks; P < .001). In comparison with white women, a longer TTC was observed among black (1.5 weeks; P < .001) and Hispanic (0.8 weeks; P < .001) women. For black women, the observed disparity was greater among women who transferred their care to the NCCN center after diagnosis (P interaction = .008) and among women with Medicare vs commercial insurance (P interaction < .001). Conclusions Most observed variation in TTC was related to use of appropriate therapeutic interventions. This suggests the importance of targeted efforts to minimize potentially preventable causes of delay, including inefficient transfers in care or prolonged appointment wait times. PMID:23264681

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Gene expression profiling for guiding adjuvant chemotherapy decisions in women with early breast cancer: an evidence-based and economic analysis.

PubMed

2010-01-01

outcome was risk of 10-year distant recurrence. The prospectively defined secondary outcome was 10-year death due to any cause (i.e., overall survival). All additional outcomes such as risk of locoregional recurrence or disease-free survival (DFS) were not prospectively determined for this review but were reported as presented in included trials; these outcomes are referenced as tertiary outcomes in this review. Outcomes for other Key Questions (i.e., Key Questions #1, #4 and #5) were not prospectively defined due to the variability in endpoints relevant for these questions. A total of 26 studies were included. Of these 26 studies, only five studies were relevant to the primary questions of this review (Key Questions #2 and #3). The following conclusions were drawn from the entire body of evidence: There is a lack of external validation to support the reliability of Oncotype-DX; however, the current available evidence derived from internal industry validation studies suggests that Oncotype-DX is reliable (i.e., Oncotype-DX is repeatable and reproducible).Current available evidence suggests a moderate failure rate of Oncotype-DX testing; however, the failure rate observed across clinical trials included in this review is likely inflated; the current Ontario experience suggests an acceptably lower rate of test failure.In women with newly diagnosed early breast cancer (stage I-II) that is estrogen-receptor positive and/or progesterone-receptor positive and lymph-node negative:There is low quality evidence that Oncotype-DX has prognostic value in women who are being treated with adjuvant tamoxifen or anastrozole (the latter for postmenopausal women only),There is very low quality evidence that Oncotype-DX can predict which women will benefit from adjuvant CMF/MF chemotherapy in women being treated with adjuvant tamoxifen.In postmenopausal women with newly diagnosed early breast cancer that is estrogen-receptor positive and/or progesterone-receptor positive and lymph

Lentinula edodes mycelia extract plus adjuvant chemotherapy for breast cancer patients: Results of a randomized study on host quality of life and immune function improvement.

PubMed

Nagashima, Yukiko; Yoshino, Shigehumi; Yamamoto, Shigeru; Maeda, Noriko; Azumi, Tatsuya; Komoike, Yoshifumi; Okuno, Kiyotaka; Iwasa, Tsutomu; Tsurutani, Junji; Nakagawa, Kazuhiko; Masaaki, Oka; Hiroaki, Nagano

2017-09-01

Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i.e., 5-fluorouracil (5-FU) + cyclophosphamide + epirubicin (FEC regimen), 5-FU + cyclophosphamide + doxorubicin/pirarubicin (FAC regimen), cyclophosphamide + doxorubicin/pirarubicin (AC regimen) and cyclophosphamide + epirubicin (EC regimen), were entered in the study. The patients were randomly divided into either an LEM or a placebo tablet group; the tablets were orally ingested daily over 2 courses of each therapy. In the placebo group, the total scores for QOL were lower on day 8 of the second course of chemotherapy compared with the baseline scores, whereas in the LEM group the scores had not decreased. In the placebo group, the QOL functional well-being score was lower on day 8 after both the first and second courses of chemotherapy compared with the baseline score, but it had not decreased in the LEM group. Evaluation of immunological parameters indicated that an increase in the proportion of regulatory T cells to peripheral blood CD4 + cells tended to be inhibited in the LEM group compared with the placebo group. Oral LEM that was coadministered with anthracycline-based chemotherapies was useful for maintaining patients' QOL and immune function. Thus, LEM appears to be a useful oral adjuvant for patients receiving anthracycline-based chemotherapy.

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,

Myelodysplastic syndrome and acute myeloid leukemia following adjuvant chemotherapy with and without granulocyte colony-stimulating factors for breast cancer

PubMed Central

Calip, Gregory S.; Malmgren, Judith A.; Lee, Wan-Ju; Schwartz, Stephen M.; Kaplan, Henry G.

2015-01-01

Purpose Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. Methods We conducted a retrospective cohort study of women ages ≥66 years with stage I-III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy and/or G-CSF. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for MDS/AML risk. Results Among 56,251 breast cancer cases, 1.2% developed MDS/AML during median follow-up of 3.2 years. 47.1% of women received radiation and 14.3% received chemotherapy. Compared to breast cancer cases treated with surgery alone, those treated with chemotherapy (HR=1.38, 95%-CI: 0.98–1.93) and chemotherapy/radiation (HR=1.77, 95%-CI: 1.25–2.51) had increased risk of MDS/AML; but not radiation alone (HR=1.08, 95% CI: 0.86–1.36). Among chemotherapy regimens and G-CSF, MDS/AML risk was differentially associated with anthracycline/cyclophosphamide-containing regimens (HR=1.86, 95%-CI: 1.33–2.61) and filgrastim (HR=1.47, 95%-CI: 1.05–2.06), but not pegfilgrastim (HR=1.10, 95%-CI: 0.73–1.66). Conclusions We observed increased MDS/AML risk among older breast cancer survivors treated with anthracycline/cyclophosphamide chemotherapy that was enhanced by G-CSF. Although small, this risk warrants consideration when determining adjuvant chemotherapy and neutropenia prophylaxis for breast cancer patients. PMID:26450505

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial.

PubMed

Seagle, Brandon-Luke L; Shahabi, Shohreh

2017-04-01

To determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. A three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. The model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97-$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. Dose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262. Copyright © 2017 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, Seth A., E-mail: rosents@sutterhealth.org; Hunt, Daniel; Sartor, A. Oliver

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.more » 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

Physical activity intensity and health status perception of breast cancer patients undergoing adjuvant chemotherapy.

PubMed

Tonosaki, Akiko; Ishikawa, Miharu

2014-04-01

The aim was to evaluate the physical activity intensity (PAI) of patients receiving adjuvant chemotherapy and investigate the relationship between health status perception and PAI in Japan. Consenting participants of this prospective, descriptive, repeated measures design were 28 women aged 20-64 with stage I-IIIA initial breast cancer whose regimen included anthracycline. Participants wore a triaxial accelerometer and their PAI was measured for a 14-day period at the beginning of chemotherapy. The SF-36 Survey and Cancer Fatigue Scale were administered. The accelerometer was used to calculate the number of steps, physical activity level (PAL) and total minutes of PAI levels of under 1.5 Mets, 1.5-2.9 Mets, and more than 3.0 Mets during the first half (FH; days 2-7) and second half (SH; days 8-14) of the study. Data were analyzed using Pearson's correlation coefficient and multiple regression analysis. During FH, the mean number of steps was 3841.1 steps/day and mean PAL was 1.43; during SH, the mean number of steps was 4058.4 steps/day, mean PAL was 1.43; participants spent over 70% of the day working quietly in a sitting position. PAL during SH was significantly associated with mean time spent during activities of 1.5-2.9 Mets (β = 0.880, p < 0.0001) and 3.0 Mets (β = 0.268, p < 0.0001). Patients receiving adjuvant chemotherapy had extremely low physical activity. They should be provided useful information of appropriate physical movement and be supported in resolving physical and psychological distress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial.

PubMed

Del Mastro, Lucia; De Placido, Sabino; Bruzzi, Paolo; De Laurentiis, Michele; Boni, Corrado; Cavazzini, Giovanna; Durando, Antonio; Turletti, Anna; Nisticò, Cecilia; Valle, Enrichetta; Garrone, Ornella; Puglisi, Fabio; Montemurro, Filippo; Barni, Sandro; Ardizzoni, Andrea; Gamucci, Teresa; Colantuoni, Giuseppe; Giuliano, Mario; Gravina, Adriano; Papaldo, Paola; Bighin, Claudia; Bisagni, Giancarlo; Forestieri, Valeria; Cognetti, Francesco

2015-05-09

Whether addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel (EC-P) is favourable in adjuvant treatment of patients with node-positive breast cancer is controversial, as is the benefit of increased density of dosing. We aimed to address these questions in terms of improvements in disease-free survival. In this 2 × 2 factorial, open-label, phase 3 trial, we enrolled patients aged 18-70 years with operable, node positive, early-stage breast cancer from 81 Italian centres. Eligible patients were randomly allocated in a 1:1:1:1 ratio with a centralised, interactive online system to receive either dose-dense chemotherapy (administered intravenously every 2 weeks with pegfilgrastim support) with fluorouracil plus EC-P (FEC-P) or EC-P or to receive standard-interval chemotherapy (administered intravenously every 3 weeks) with FEC-P or EC-P. The primary study endpoint was disease-free survival, assessed with the Kaplan-Meier method in the intention-to-treat population. Our primary comparisons were between dose schedule (every 2 weeks vs every 3 weeks) and dose type (FEC-P vs EC-P). This study is registered with ClinicalTrials.gov, number NCT00433420. Between April 24, 2003, and July 3, 2006, we recruited 2091 patients. 88 patients were enrolled in centres that only provided standard-intensity dosing. After a median follow-up of 7·0 years (interquartile range [IQR] 4·5-6·3), 140 (26%) of 545 patients given EC-P every 3 weeks, 157 (29%) of 544 patients given FEC-P every 3 weeks, 111 (22%) of 502 patients given EC-P every 2 weeks, and 113 (23%) of 500 patients given FEC-P every 2 weeks had a disease-free survival event. For the dose-density comparison, disease-free survival at 5 years was 81% (95% CI 79-84) in patients treated every 2 weeks and 76% (74-79) in patients treated every 3 weeks (HR 0·77, 95% CI 0·65-0·92; p=0·004); overall survival rates at 5 years were 94% (93-96) and 89% (87-91; HR 0·65, 0·51-0·84; p=0·001) and for the

The Use of a Cognitive Protectant to Help Maintain Quality of Life and Cognition in Premenopausal Women with Breast Cancer Undergoing Adjuvant Chemotherapy

DTIC Science & Technology

2006-10-01

Significant reductions in quality of life and cognitive function are experienced by women with breast cancer receiving adjuvant chemotherapy. These...little data are available regarding younger women’s cognitive function and quality of life during chemotherapy. The goal of the proposed study is to...examine change in cognitive function and quality of life in 30 pre-menopausal women with breast cancer receiving chemotherapy. To determine if accelerated

The influence of non-clinical patient factors on medical oncologists' decisions to recommend breast cancer adjuvant chemotherapy.

PubMed

Pini, T May; Hawley, Sarah T; Li, Yun; Katz, Steven J; Griggs, Jennifer J

2012-07-01

The extent to which medical oncologists consider non-clinical patient factors when deciding to recommend adjuvant chemotherapy is unknown. Medical oncologists who treated a population-based sample of early stage breast cancer patients reported to the Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries 2005-2007 were asked how strongly they consider a patient's ability to follow instructions, level of social support, and level of work support/flexibility in decisions to recommend adjuvant chemotherapy. Responses of 4 (Quite strongly) or 5 (Very strongly) on a five-point Likert scale defined strong consideration. Associations between oncologist/practice characteristics and strong consideration of each non-clinical factor were examined. 134 oncologists (66 %) reported strong consideration of one or more factor. Ability to follow instructions was strongly considered by 120 oncologists (59 %), social support by 78 (38 %), and work support/flexibility by 73 (36 %). Larger percent of practice devoted to breast cancer was associated with lower likelihood of strongly considering ability to follow instructions [odds ratio (OR) 0.98, 95 % confidence interval (CI) 0.97-0.99; P = 0.04]. Increased years in practice was associated with lower likelihood of strongly considering social support (OR 0.96, CI 0.93-0.99; P = 0.011), while non-white race (OR 2.1, CI 1.03-4.26; P = 0.041) and tumor board access (OR 2.04, CI 1.01-4.12; P = 0.048) were associated with higher likelihood. Non-white race was associated with strongly considering work support/flexibility (OR 2.44, CI 1.21-4.92; P = 0.013). Tumor board access (OR 2, CI 1.00-4.02; P = 0.051) was borderline significant. Non-clinical patient factors play a role in medical oncologist decision-making for breast cancer adjuvant chemotherapy recommendations.

Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials

PubMed Central

Dieci, M. V.; Mathieu, M. C.; Guarneri, V.; Conte, P.; Delaloge, S.; Andre, F.; Goubar, A.

2015-01-01

Background Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. Patients and methods A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. Results TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95 P = 0.003; HR 0.89, 95% CI 0.81–0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18–1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20–1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2−, HER2+, ER−/HER2−). Conclusions We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic

Side Effects of Standard Adjuvant and Neoadjuvant Chemotherapy Regimens According to Age Groups in Primary Breast Cancer

PubMed Central

Reinisch, Mattea; von Minckwitz, Gunter; Harbeck, Nadia; Janni, Wolfgang; Kümmel, Sherko; Kaufmann, Manfred; Elling, Dirk; Nekljudova, Valentina; Loibl, Sibylle

2013-01-01

Summary Background Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination. Patients and Methods In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age. Results Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60–64 years and 10.6% were > 64 years. The patients’ compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC-and dd-doxorubicin/docetaxel-treated groups. Conclusion The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years. PMID:24715845

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. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

PubMed

Lesiuk, Teresa

2015-05-01

To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer.

PubMed

Norton, Nadine; Fox, Nicholas; McCarl, Christie-Ann; Tenner, Kathleen S; Ballman, Karla; Erskine, Courtney L; Necela, Brian M; Northfelt, Donald; Tan, Winston W; Calfa, Carmen; Pegram, Mark; Colon-Otero, Gerardo; Perez, Edith A; Clynes, Raphael; Knutson, Keith L

2018-06-14

Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival. Prior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04). These results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting. ClinicalTrials.gov, NCT00005970 . Registered on July

Same gain, less pain: potential patient preferences for adjuvant treatment in premenopausal women with early breast cancer.

PubMed

Fallowfield, Lesley; McGurk, Rhona; Dixon, Michael

2004-11-01

The aim of this study was to determine the treatment preferences (adjuvant goserelin or cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy) of healthy premenopausal women should they hypothetically develop oestrogen-receptor (ER) positive early breast cancer. Two hundred pre or peri-menopausal women read two scenarios describing goserelin or chemotherapy. Information included: How and where treatments were administered, side-effects, their likely persistence and impact on fertility. Women stated their unprompted initial and final preferences with reasons for the choices made. Respondents showed an overwhelming preference for goserelin. 156 (78%) women favoured goserelin, 22 (11%) chemotherapy and 22 (11%) remained undecided (P<0.0001). Primary reasons for preferring goserelin for were 105 (71%) avoidance of chemotherapy side-effects, especially hair loss, perceived convenience and less disruption to normal life 54 (36%). The minority who preferred chemotherapy, valued the treatment finishing more quickly. These results together with clinical trial data showing equivalence of goserelin with CMF regimens suggest that premenopausal women with ER-positive tumours should at least be offered the choice of either adjuvant hormone therapy or chemotherapy.

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

PubMed

André, Thierry; Vernerey, Dewi; Mineur, Laurent; Bennouna, Jaafar; Desrame, Jérôme; Faroux, Roger; Fratte, Serge; Hug de Larauze, Marine; Paget-Bailly, Sophie; Chibaudel, Benoist; Bez, Jeremie; Dauba, Jérôme; Louvet, Christophe; Lepere, Céline; Dupuis, Olivier; Becouarn, Yves; Mabro, May; Egreteau, Joëlle; Bouche, Olivier; Deplanque, Gaël; Ychou, Marc; Galais, Marie Pierre; Ghiringhelli, François; Dourthe, Louis Marie; Bachet, Jean-Baptiste; Khalil, Ahmed; Bonnetain, Franck; de Gramont, Aimery; Taieb, Julien

2018-05-20

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared

An Observational Study to Examine Changes in Metabolic Syndrome Components in Breast Cancer Patients Receiving Neoadjuvant or Adjuvant Chemotherapy

PubMed Central

Dieli-Conwright, Christina M.; Wong, Louise; Waliany, Sarah; Bernstein, Leslie; Salehian, Behrouz; Mortimer, Joanne E.

2016-01-01

BACKGROUND We sought to determine the effect of chemotherapy on the development of metabolic syndrome (MetS) in premenopausal and postmenopausal women undergoing (neo) adjuvant therapy for early stage breast cancer. METHODS Eighty-six women with early stage (I-III) breast cancer who were free from clinically diagnosed MetS (defined as three out of five components of MetS) were prospectively tested for presence of the five components of MetS within one week before initiating and after completing (neo) adjuvant chemotherapy. The five components of MetS measured were waist circumference, blood pressure, and fasting levels of blood glucose, triglycerides, and high-density lipoprotein cholesterol. Anthropometrics (body weight, percent body fat, fat mass), lipid profile (total cholesterol, low-density lipoprotein cholesterol), glucose metabolism (insulin, homeostatic model assessment-insulin resistance, glycated hemoglobin), and inflammation (C-reactive protein) were also examined before initiating and after completing treatment. RESULTS The study included 46 premenopausal and 40 postmenopausal women. All individual MetS components and overall MetS score were statistically significantly increased (p<0.01) after chemotherapy. Body weight, percent body fat, fat mass, lipids, glucose metabolism, and inflammation were also statistically significantly increased (p<0.01). CONCLUSION A 12–18 week course of chemotherapy statistically significantly increases MetS and related anthropometrics, biomarkers of glucose metabolism, and inflammation in early stage breast cancer patients with no pre-existing MetS. Lifestyle interventions such as diet and exercise may be preventive approaches to employ during chemotherapy to reduce the onset of MetS in breast cancer patients. PMID:27219902

The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

PubMed Central

2011-01-01

Background Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. Methods A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. Results CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022). Conclusions Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results. PMID:21827707

Adjuvant radiation trials for high-risk breast cancer patients: adequacy of lymphadenectomy.

PubMed

Silberman, A W; Sarna, G P; Palmer, D

2000-06-01

The recently published, widely publicized adjuvant radiation trials from Denmark and Canada concluded that the addition of postoperative radiotherapy (XRT) to modified radical mastectomy (MRM) and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal patients with breast cancer. Our thesis is that adequate lymphadenectomies were not performed in either study. Consequently, the conclusion to these studies is not applicable to those patients who have undergone adequate surgery. To better assess adequate lymph node yield from an MRM, a retrospective review was performed on 215 consecutive patients treated surgically for invasive breast cancer. Data from this review were compared with the surgical data from the above-mentioned radiotherapy trials. In a group of 131 patients who had MRM, the average number of nodes removed was 26 (median, 25), and 75.5% of the specimens had 20 or more lymph nodes. In 73 patients who underwent segmental mastectomy with axillary lymph node dissection, both the average and the median number of lymph nodes removed were 24, and 68.9% had 20 or more nodes. These data compare to the Danish radiation trial in which a median of 7 lymph nodes were removed (with 76% of the patients having 9 or fewer lymph nodes in the specimen) and to the Canadian radiation trial in which a median of 11 lymph nodes were removed. In addition, in our breast cancer patients with positive nodes (84 of 204; 41.2%), 45.2.% (38 of 84) had more than three positive nodes compared with 29.8% in the Danish study and 35% in the Canadian study. Our surgical data are sufficiently different from those of the Danish and Canadian studies to indicate that, in those studies, incomplete lymph node dissections were performed and that residual disease was left behind in the axilla in some or all of the patients. The addition of XRT in the setting of residual axillary disease may compensate for an inadequate operation and yield an

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial.

PubMed

Gupta, Sudeep; Maheshwari, Amita; Parab, Pallavi; Mahantshetty, Umesh; Hawaldar, Rohini; Sastri Chopra, Supriya; Kerkar, Rajendra; Engineer, Reena; Tongaonkar, Hemant; Ghosh, Jaya; Gulia, Seema; Kumar, Neha; Shylasree, T Surappa; Gawade, Renuka; Kembhavi, Yogesh; Gaikar, Madhuri; Menon, Santosh; Thakur, Meenakshi; Shrivastava, Shyam; Badwe, Rajendra

2018-06-01

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability.

PubMed

Bigaeva, Emilia; Doorn, Eva van; Liu, Heng; Hak, Eelko

2016-01-01

QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™) from vaccine trials. A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs) of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using a random-effects model. Jadad scale was used to assess the study quality. Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04-6.24). No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10-15.35 and RR 2.55, 95% CI 1.41-4.59, respectively). ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08-10.97). Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non-healthy subjects. This meta-analysis is limited by the relatively

TPOAb and Thyroid Function Are Not Associated with Breast Cancer Outcome: Evidence from a Large-Scale Study Using Data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001)

PubMed Central

Muller, Ilaria; Kilburn, Lucy S.; Taylor, Peter N.; Barrett-Lee, Peter J.; Bliss, Judith M.; Ellis, Paul; Ludgate, Marian E.; Dayan, Colin M.

2017-01-01

Background Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. Objectives We aimed to clarify this association in a large cohort using the phase III, randomized, controlled Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Methods TACT women >18 years old with node-positive or high-risk node-negative early breast cancer (pT1–3a, pN0–1, M0), with stored plasma (n = 1,974), taken 15.5 (median; IQR 7.0–24.0) months after breast surgery were studied. Patients had also received chemotherapy (100%), radiotherapy (1,745/1,974; 88.4%), hormonal therapy (1,378/ 1,974; 69.8%), or trastuzumab (48/1,974; 2.4%). History of thyroid diseases and/or related treatments was not available. The prognostic significance of autoantibodies to thyroid peroxidase (TPOAb; positive ≥6 kIU/L), free-thyroxine and thyrotropin (combined: euthyroid, hypothyroid, hyperthyroid) was evaluated for disease-free survival (DFS), overall-survival (OS), and time-to-recurrence (TTR), with Cox regression models in univariate and multivariable analyses. The extended median follow-up was 97.5 months. Results No difference in DFS was found by TPOAb status (unadjusted hazard ratio [HR]: 0.97, 95%CI: 0.78–1.19; p = 0.75) and/or thyroid function (unadjusted HR [hypothyroid vs. euthyroid]: 1.15, 95% CI: 0.79–1.68; p = 0.46; unadjusted HR [hyperthyroid vs. euthyroid]: 1.14, 95% CI: 0.82–1.61; p = 0.44). Similar results were obtained for OS, TTR, multivariable analyses, when TPOAb titre by tertiles was considered, and in a subgroup of 123 patients with plasma collected before adjuvant treatments. Conclusions No evidence for a prognostic role of TPOAb and/or thyroid function in moderate-to-high-risk early breast cancer was found in the largest and longest observational study to date. PMID:28868260

Use of a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer: development and preliminary evaluation.

PubMed

Miles, A; Chronakis, I; Fox, J; Mayer, A

2017-03-24

To develop a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer, and examine perceived usefulness, acceptability and areas for improvement of the DA. Mixed methods. Single outpatient oncology department in central London. Consecutive recruitment of 13 patients with stage II colorectal cancer, 12 of whom completed the study. Inclusion criteria were: age >18 years; complete resection for stage II adenocarcinoma of the colon or rectum; patients within 14-56 days after surgery; no contraindication to adjuvant chemotherapy; able to give written informed consent. Exclusion criterion: previous chemotherapy. Patient perceived usefulness (assessed by the PrepDM questionnaire) and acceptability of the DA. PrepDM scores, measuring the perceived usefulness of the DA in preparing the patient to communicate with their doctor and make a health decision, were above those reported in other patient groups. Patient acceptability scores were also high; however, interviews showed that there was evidence of a lack of understanding of key information among some patients, in particular their baseline risk of recurrence, the net benefit of combination chemotherapy and the rationale for having chemotherapy when cancer had apparently gone. Patients found the DA acceptable and useful in supporting their decision about whether or not to have adjuvant chemotherapy. Suggested improvements for the DA include: sequential presentation of treatment options (eg, no treatment vs 1 drug, 1 drug vs 2 drugs) to enhance patient understanding of the difference between combination and single therapy, diagrams to help patients understand the rationale for chemotherapy to prevent a recurrence and inbuilt checks on patient understanding of baseline risk of recurrence and net benefit of chemotherapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial.

PubMed

Reni, Michele; Balzano, Gianpaolo; Zanon, Silvia; Zerbi, Alessandro; Rimassa, Lorenza; Castoldi, Renato; Pinelli, Domenico; Mosconi, Stefania; Doglioni, Claudio; Chiaravalli, Marta; Pircher, Chiara; Arcidiacono, Paolo Giorgio; Torri, Valter; Maggiora, Paola; Ceraulo, Domenica; Falconi, Massimo; Gianni, Luca

2018-06-01

Pancreatic ductal adenocarcinoma are known to metastasise early and a rationale exists for the investigation of preoperative chemotherapy in patients with resectable disease. We aimed to assess the role of combination chemotherapy in this setting in the PACT-15 trial. We did this randomised, open-label, phase 2-3 trial in ten hospitals in Italy. We report the phase 2 part here. Patients aged 18-75 years who were previously untreated for pancreatic ductal adenocarcinoma, with Karnofsky performance status of more than 60, and pathologically confirmed stage I-II resectable disease were enrolled. Patients were randomly assigned (1:1:1), with a minimisation algorithm that stratified treatment allocation by centre and concentrations of carbohydrate antigen 19-9 (CA19-9 ≤5 × upper limit of normal [ULN] vs >5 × ULN), to receive surgery followed by adjuvant gemcitabine 1000 mg/m 2 on days 1, 8, 15 every 4 weeks for six cycles (arm A), surgery followed by six cycles of adjuvant PEXG (cisplatin 30 mg/m 2 , epirubicin 30 mg/m 2 , and gemcitabine 800 mg/m 2 on days 1 and 15 every 4 weeks and capecitabine 1250 mg/m 2 on days 1-28; arm B), or three cycles of PEXG before and three cycles after surgery (arm C). Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation. The primary endpoint was the proportion of patients who were event-free at 1 year. The primary endpoint was analysed in the per-protocol population. Safety analysis was done for all patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, number NCT01150630. Between Oct 5, 2010, and May 30, 2015, 93 patients were randomly allocated to treatment. One centre was found to be non-compliant with the protocol, and all five patients at this centre were excluded from the study. Thus, 88 patients were included in the final study population: 26 in group A, 30 in group B, and 32 in group C. In the per

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.

PubMed

Gao, Sarah J; Corso, Christopher D; Blasberg, Justin D; Detterbeck, Frank C; Boffa, Daniel J; Decker, Roy H; Kim, Anthony W

2017-03-01

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC). Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment. Kaplan-Meier and log-rank tests were used to compare overall survival, and a bootstrapped Cox proportional hazards model was used to determine the significant contributors to survival. A subset analysis was performed with stratification by margin status and tumor size. Of 759 patients identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and 12.3% underwent surgery followed by radiotherapy alone. Tumors > 4 cm benefited from adjuvant chemotherapy and radiation therapy in the multivariable analysis, and those ≤ 4 cm benefited only from adjuvant chemotherapy. The subgroup analysis by margin status identified that margin-positive patients with tumors > 4 cm benefited significantly from either adjuvant chemoradiation therapy or radiation therapy alone. T3N0 NSCLC with chest wall invasion requires unique management compared with other stage IIB tumors. An important determinant of management is tumor size, with tumors ≤ 4 cm benefiting from adjuvant chemotherapy and tumors > 4 cm benefiting from adjuvant chemotherapy if margin negative and adjuvant chemoradiation therapy or radiotherapy if margin positive. Copyright © 2016 Elsevier Inc. All rights reserved.

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

PubMed

Garlipp, Benjamin; Ptok, Henry; Benedix, Frank; Otto, Ronny; Popp, Felix; Ridwelski, Karsten; Gastinger, Ingo; Benckert, Christoph; Lippert, Hans; Bruns, Christiane

2016-12-01

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

[Primary safety analysis of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients].

PubMed

Zhou, Ning-Ning; Teng, Xiao-Yu; Liu, Dong-Geng; Xu, Ran; Guan, Zhong-Zhen

2008-12-01

It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients. Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed. Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed. The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.

Singapore Cancer Network (SCAN) Guidelines for Adjuvant Chemotherapy in Resected Non-Small Cell Lung Cancer.

PubMed

2015-10-01

The SCAN lung cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for the use of adjuvant systemic therapy for non-small cell lung cancer in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), European Society of Medical Oncology (2014), National Institute of Clinical Excellence (2012), Scottish Intercollegiate Guidelines Network (2014), and the Cancer Care Council Australia (2012). Recommendations on the selection of patients, chemotherapy regimen, treatment for stage I disease, treatment for positive margins and treatment options for pN2 disease with negative margins were produced. These adapted guidelines form the SCAN Guidelines 2015 for adjuvant systemic therapy of non-small cell lung cancer.

Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer.

PubMed

Garrison, Louis P; Lubeck, Deborah; Lalla, Deepa; Paton, Virginia; Dueck, Amylou; Perez, Edith A

2007-08-01

Adding trastuzumab to adjuvant chemotherapy provides significant clinical benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A cost-effectiveness analysis was performed to assess clinical and economic implications of adding trastuzumab to adjuvant chemotherapy, based upon joint analysis of NSABP B-31 and NCCTG N9831 trials. A Markov model with 4 health states was used to estimate the cost utility for a 50-year-old woman on the basis of trial results through 4 years and estimates of long-term recurrence and death based on a meta-analysis of trials. From 6 years onward, rates of recurrence and death were assumed to be the same in both trastuzumab and chemotherapy-only arms. Incremental costs were estimated for diagnostic and treatment-related costs. Analyses were from payer and societal perspectives, and these analyses were projected to lifetime and 20-year horizons. Over a lifetime, the projected cost of trastuzumab per quality-adjusted life year (QALY; discount rate 3%) gained was 26,417 dollars (range 9,104 dollars-69,340 dollars under multiway sensitivity analysis). Discounted incremental lifetime cost was 44,923 dollars, and projected life expectancy was 3 years longer for patients who received trastuzumab (19.4 years vs 16.4 years). During a 20-year horizon, the projected cost of adding trastuzumab to chemotherapy was 34,201 dollars per QALY gained. Key cost-effectiveness drivers were discount rate, trastuzumab price, and probability of metastasis. The cost-effectiveness result was robust to sensitivity analysis. Trastuzumab for adjuvant treatment of early stage breast cancer was projected to be cost effective over a lifetime horizon, achieving a cost-effectiveness ratio below that of many widely accepted oncology treatments. (c) 2007 American Cancer Society.

Phase II randomized trial comparing high-dose IFN-α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected mucosal melanoma.

PubMed

Lian, Bin; Si, Lu; Cui, Chuanliang; Chi, Zhihong; Sheng, Xinan; Mao, Lili; Li, Siming; Kong, Yan; Tang, Bixia; Guo, Jun

2013-08-15

Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected mucosal melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Patients with mucosal melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10(6) U/m(2)/d IFN-α2b, followed by 9 × 10(6) U IFN-α2b), and temozolomide (200 mg/m(2)/d) plus cisplatin (75 mg/m(2)) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS (P < 0.001) and OS (P < 0.01) than those treated with either HDI or surgery alone. Toxicities were generally mild to moderate. Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected mucosal melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected mucosal melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected mucosal melanoma. ©2013 AACR.

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients

PubMed Central

Jiao, Lijing; Dong, Changsheng; Liu, Jiaxiang; Chen, Zhiwei; Zhang, Lei; Xu, Jianfang; Shen, Xiaoyong; Che, Jiaming; Yang, Yi; Huang, Hai; Li, Hegen; Sun, Jianli; Jiang, Yi; Mao, Zhujun; Chen, Peiqi; Gong, Yabin; Jin, Xiaolin; Xu, Ling

2017-01-01

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens. PMID:28436479

Value of Information Analysis of Multiparameter Tests for Chemotherapy in Early Breast Cancer: The OPTIMA Prelim Trial.

PubMed

Hall, Peter S; Smith, Alison; Hulme, Claire; Vargas-Palacios, Armando; Makris, Andreas; Hughes-Davies, Luke; Dunn, Janet A; Bartlett, John M S; Cameron, David A; Marshall, Andrea; Campbell, Amy; Macpherson, Iain R; Dan Rea; Francis, Adele; Earl, Helena; Morgan, Adrienne; Stein, Robert C; McCabe, Christopher

2017-12-01

Precision medicine is heralded as offering more effective treatments to smaller targeted patient populations. In breast cancer, adjuvant chemotherapy is standard for patients considered as high-risk after surgery. Molecular tests may identify patients who can safely avoid chemotherapy. To use economic analysis before a large-scale clinical trial of molecular testing to confirm the value of the trial and help prioritize between candidate tests as randomized comparators. Women with surgically treated breast cancer (estrogen receptor-positive and lymph node-positive or tumor size ≥30 mm) were randomized to standard care (chemotherapy for all) or test-directed care using Oncotype DX™. Additional testing was undertaken using alternative tests: MammaPrint TM , PAM-50 (Prosigna TM ), MammaTyper TM , IHC4, and IHC4-AQUA™ (NexCourse Breast™). A probabilistic decision model assessed the cost-effectiveness of all tests from a UK perspective. Value of information analysis determined the most efficient publicly funded ongoing trial design in the United Kingdom. There was an 86% probability of molecular testing being cost-effective, with most tests producing cost savings (range -£1892 to £195) and quality-adjusted life-year gains (range 0.17-0.20). There were only small differences in costs and quality-adjusted life-years between tests. Uncertainty was driven by long-term outcomes. Value of information demonstrated value of further research into all tests, with Prosigna currently being the highest priority for further research. Molecular tests are likely to be cost-effective, but an optimal test is yet to be identified. Health economics modeling to inform the design of a randomized controlled trial looking at diagnostic technology has been demonstrated to be feasible as a method for improving research efficiency. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial.

PubMed

Sinn, Marianne; Bahra, Marcus; Liersch, Torsten; Gellert, Klaus; Messmann, Helmut; Bechstein, Wolf; Waldschmidt, Dirk; Jacobasch, Lutz; Wilhelm, Martin; Rau, Bettina M; Grützmann, Robert; Weinmann, Arndt; Maschmeyer, Georg; Pelzer, Uwe; Stieler, Jens M; Striefler, Jana K; Ghadimi, Michael; Bischoff, Sven; Dörken, Bernd; Oettle, Helmut; Riess, Hanno

2017-10-10

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m 2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

PubMed

Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

2017-09-01

Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women <40 years at diagnosis (HR = 1.13, 95% CI 0.69-1.84) who are less likely to develop chemotherapy-induced amenorrhea. Based on

Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

PubMed

Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

2015-06-01

For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care?

PubMed

Almhanna, Khaldoun; Shridhar, Ravi; Meredith, Kenneth L

2013-04-01

Carcinoma of the esophagus is an aggressive and lethal disease with an increasing incidence worldwide. Despite changes in the treatment approach over the past two decades and even following complete resection, most patients will eventually relapse and die as a result of their disease. Several clinical trials evaluated different modalities in treating locally advanced esophageal cancer; however, because of stage migration and the changes in disease epidemiology, applying these trials to clinical practice has become a daunting task. We searched Medline and conference abstracts for randomized studies published in the past three decades. We restricted our search to articles published in English. Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States for patients with locally advanced esophageal cancer. Esophagectomy remains an essential component of treatment and can lead to improved overall survival, especially when performed at high-volume institutions. The role of adjuvant chemotherapy following curative resection in patients who underwent neoadjuvant chemotherapy and radiation remains unclear. Several questions still need to be answered regarding the use of neoadjuvant or adjuvant therapy for patients with resectable esophageal cancer. The optimal chemotherapy regimen has not yet been identified for these patients, although newer therapies show promise.

Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer.

PubMed

Schramm, Amelie; Schochter, Fabienne; Friedl, Thomas W P; de Gregorio, Nikolaus; Andergassen, Ulrich; Alunni-Fabbroni, Marianna; Trapp, Elisabeth; Jaeger, Bernadette; Heinrich, Georg; Camara, Oumar; Decker, Thomas; Ober, Angelika; Mahner, Sven; Fehm, Tanja N; Pantel, Klaus; Fasching, Peter A; Schneeweiss, Andreas; Janni, Wolfgang; Rack, Brigitte K

2017-07-01

Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics). Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18). The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary

Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

PubMed Central

Rabanal, Connie; Ruiz, Rossana; Neciosup, Silvia; Gomez, Henry

2017-01-01

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer, and is still defined as what it is not. Currently, TNBC is the only type of breast cancer for which there are no approved targeted therapies and maximum tolerated dose chemotherapy with taxanes and anthracycline-containing regimens is still the standard of care in both the neoadjuvant and adjuvant settings. In the last years, metronomic chemotherapy (MC) is being explored as an alternative to improve outcomes in TNBC. In the neoadjuvant setting, purely metronomic and hybrid approaches have been developed with the objective of increasing complete pathologic response (pCR) and prolonging disease free survival. These regimens proved to be very effective achieving pCR rates between 47%-60%, but at the cost of great toxicity. In the adjuvant setting, MC is used to intensify adjuvant chemotherapy and, more promisingly, as maintenance therapy for high-risk patients, especially those with no pCR after neoadjuvant chemotherapy. Considering the dismal prognosis of TNBC, any strategy that potentially improves outcomes, specially being the oral agents broadly available and inexpensive, should be considered and certainly warrants further exploration. Finally, the benefit of MC needs to be validated in properly designed clinical trials were the selection of the population is the key. PMID:29291168

Anti-Müllerian hormone (AMH) levels in premenopausal breast cancer patients treated with taxane-based adjuvant chemotherapy - A translational research project of the SUCCESS A study.

PubMed

Trapp, Elisabeth; Steidl, J; Rack, B; Kupka, M S; Andergassen, U; Jückstock, J; Kurt, A; Vilsmaier, T; de Gregorio, A; de Gregorio, N; Tzschaschel, M; Lato, C; Polasik, A; Tesch, H; Schneeweiss, A; Beckmann, M W; Fasching, P A; Janni, W; Müller, V

2017-10-01

Premenopausal women undergoing chemotherapy are at high risk for premature ovarian failure and its long-term consequences. Data on potential markers to evaluate ovarian reserve pre- and posttreatment are limited. Anti-Müllerian hormone (AMH) known for ovarian reserve in reproductive medicine could be a surrogate marker and was assessed in premenopausal breast cancer patients of the SUCCESS A study (EUDRA-CT no. 2005-000490-21). We identified 170 premenopausal patients, age ≤ 40 years at trial entry, who received FEC-Doc as taxane-anthracylince based chemotherapy. Blood samples were taken at three time points: Before, four weeks after and two years after adjuvant chemotherapy. Serum AMH-levels were evaluated in a central laboratory by a quantitative immunoassay AMH Gen II ELISA (Beckman Coulter, Brea, USA). Median age was 36 years (21-40 years). Median serum AMH-level before chemotherapy was 1.37 ng/ml (range < 0.1-11.3 ng/ml). Four weeks after chemotherapy AMH-levels dropped in 98.6% of the patients to <0.1 ng/ml (range < 0.1-0.21 ng/ml). After two years, 73.3% (n = 101) showed no evidence of ovarian function recovery (AMH <0.1 ng/ml, range < 0.1-3.9 ng/ml). Permanent chemotherapy induced amenorrhea occurred only in 50.6% of the patients. In this analysis, premenopausal patients showed a high rate of ovarian impairment reflected by low AMH-levels after chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause.

PubMed

Chirgwin, Jacquie; Sun, Zhuoxin; Smith, Ian; Price, Karen N; Thürlimann, Beat; Ejlertsen, Bent; Bonnefoi, Hervé; Regan, Meredith M; Goldhirsch, Aron; Coates, Alan S

2012-01-01

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤ 55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤ 55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause

PubMed Central

Sun, Zhuoxin; Smith, Ian; Price, Karen N.; Thürlimann, Beat; Ejlertsen, Bent; Bonnefoi, Hervé; Regan, Meredith M.; Goldhirsch, Aron; Coates, Alan S.

2016-01-01

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients. PMID:21892704

Expression characteristic of CXCR1 in different breast tissues and the relevance between its expression and efficacy of neo-adjuvant chemotherapy in breast cancer.

PubMed

Xue, Miao-Qun; Liu, Jun; Sang, Jian-Feng; Su, Lei; Yao, Yong-Zhong

2017-07-25

To investigate chemokine receptor CXCR1 expression characteristic in different breast tissues and analyze the relationship between CXCR1 expression changes in breast cancer tissue and efficacy of neo-adjuvant chemotherapy. Chemokine receptor CXCR1 was lowly expressed in normal breast tissues and breast fibroadenoma, but highly expressed in breast cancer. It was significantly correlated with pathological stage, tumor cell differentiation, and lymph node metastasis (P < 0.05). After neo-adjuvant chemotherapy, CXCR1 expression in breast cancer tissues decreased. Among these 104 breast cancer patients with different molecular subtypes, the survival rate with Luminal A was the highest, followed by the Luminal B breast cancer, TNBC was the worst. 104 cases with breast carcinoma, 20 cases with normal breast and 20 cases with breast fibroadenoma were included and followed up. Immunohistochemistry was used to detect the expression of CXCR1 in the various tissues. The relationship between the CXCR1 expression changes in breast cancer biopsies and surgical specimens, as well as the efficacy of neo-adjuvant chemotherapy, was analyzed. Chemokine receptor CXCR1 could be used as an indicator to predict benign or malignant breast disease, and it can even predict the malignancy degree of breast cancer, as well as its invasive ability and prognosis.

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability

PubMed Central

Bigaeva, Emilia; van Doorn, Eva; Liu, Heng; Hak, Eelko

2016-01-01

Background and Objectives QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™) from vaccine trials. Methods A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs) of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using a random-effects model. Jadad scale was used to assess the study quality. Results Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04–6.24). No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10–15.35 and RR 2.55, 95% CI 1.41–4.59, respectively). ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08–10.97). Conclusions Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non

Feasibilty of a sleep intervention during adjuvant breast cancer chemotherapy.

PubMed

Berger, Ann M; VonEssen, Susanna; Khun, Brett R; Piper, Barbara F; Farr, Lynne; Agrawal, Sangeeta; Lynch, James C; Higginbotham, Patti

2002-01-01

To evaluate the feasibility of an intervention designed to promote sleep and modify fatigue during four cycles of adjuvant breast cancer chemotherapy. Prospective, repeated measures, quasi-experimental feasibility study. Midwestern urban oncology clinics. 25 women between the ages of 40-65 (mean = 54.3) with stage I-II breast cancer receiving doxorubicin-based chemotherapy. Each woman developed, reinforced, and revised an individualized sleep promotion plan (ISPP) with four components: sleep hygiene, relaxation therapy, stimulus control, and sleep restriction techniques. A daily diary, the Pittsburgh Sleep Quality Index, a wrist actigraph, and the Piper Fatigue Scale were used to collect data two days before and seven days after each treatment. Adherence, sleep and wake outcomes, and fatigue. Adherence rates with the components of the ISPP varied during treatments one through four: sleep hygiene (68%-78%), relaxation therapy (57%-67%), stimulus control (46%-67%), and sleep restriction (76%-80%). Mean sleep and wake outcomes at baseline, peak, and rebound times were that (a) sleep latency remained brief (less than 30 minutes per night), (b) time awake after sleep onset exceeded the desired less than 30 minutes per night, (c) sleep efficiency scores remained stable at 85%-90%, (d) total rest time remained stable at 8-10 hours per night, (e) subjective ratings of feelings on arising were stable, and (f) nighttime awakenings were 8-10 per night. Fatigue outcomes were that fatigue was stable two days after each treatment and mean daily fatigue intensity was lower at treatment three than at treatment one but rebounded at treatment four. The intervention was feasible, adherence rates improved over time, and most sleep and wake patterns were consistent with normal values. Revisions will focus on decreasing nighttime awakenings. Adopting behaviors to promote sleep may assist in maintaining sleep and managing fatigue during chemotherapy.

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.

A cohort study of ethnic differences in use of adjuvant chemotherapy and radiation therapy for breast cancer in New Zealand.

PubMed

Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Lawrenson, Ross

2017-01-21

Ethnic and socioeconomic inequities in use of breast cancer adjuvant therapy are well documented in many countries including the USA, and are known to contribute to lower breast cancer survival among minority ethnic and socioeconomically deprived women. We investigated ethnic and socioeconomic inequities in use of adjuvant radiotherapy and chemotherapy in a cohort of women with invasive breast cancer in New Zealand. All women with newly diagnosed invasive breast cancer during 1999-2012 were identified from the Waikato Breast Cancer Register. Rates of chemotherapy use and radiotherapy use were assessed in women who were deemed to be eligible for chemotherapy (n = 1212) and radiotherapy (n = 1708) based on guidelines. Factors associated with use of chemotherapy and radiation therapy were analysed in univariate and multivariate regression models, adjusting for covariates. Overall, rates of chemotherapy and radiotherapy use were 69% (n = 836) and 87.3% (n = 1491), respectively. In the multivariate model, significantly lower rates of radiotherapy use were associated with Māori compared with NZ European (Odds Ratio [OR] = 0.63, 0.40-0.98), presence of comorbidity (OR = 0.49, 0.34-0.72), distance from hospital of over 100km (OR = 0.47, 0.23-0.96), mastectomy compared with breast conserving surgery (OR = 0.32, 0.17-0.56) and non-screen compared with screen detection (OR = 0.53, 0.35-0.79). No significant associations were observed between chemotherapy use and ethnic or socio-demographic factors. Improving access for radiotherapy, especially for women who are at a higher risk of not receiving optimum cancer therapy due to ethnicity, geography or socioeconomic status need to be recognized as a priority to reduce inequities in breast cancer care in New Zealand.

Impact of Adjuvant Chemotherapy on Long-Term Employment of Early-Stage Breast Cancer Survivors

PubMed Central

Jagsi, Reshma; Hawley, Sarah T.; Abrahamse, Paul; Li, Yun; Janz, Nancy K.; Griggs, Jennifer J.; Bradley, Cathy; Graff, John J.; Hamilton, Ann S.; Katz, Steven J.

2014-01-01

Background Many women with early-stage breast cancer are working at the time of diagnosis and survive without recurrence. The short-term impact of chemotherapy receipt on employment has been demonstrated, but the long-term impact merits further research. Methods We conducted a longitudinal multicenter cohort study of women diagnosed with non-metastatic breast cancer in 2005–2007, as reported to the population-based Los Angeles and Detroit SEER registries. Of 3133 individuals sent surveys, 2290 (73%) completed a baseline survey soon after diagnosis and 1536 (68%) completed a four-year follow-up questionnaire. Results Of the 1026 patients aged <65 at diagnosis whose breast cancer did not recur and who responded to both surveys, 746 (76%) worked for pay before diagnosis. Of these, 236 (30%) were no longer working at follow-up. Women who received chemotherapy as part of initial treatment were less likely to work at follow-up (38% vs. 27%, p=0.003). Chemotherapy receipt at the time of diagnosis (OR 1.4, p=0.04) was independently associated with unemployment during survivorship in a multivariable model. Many women who were not employed in the survivorship period wanted to work: 50% reported that it was important for them to work and 31% were actively seeking work. Conclusions Unemployment among breast cancer survivors four years after diagnosis is often undesired and appears related to the receipt of chemotherapy during initial treatment. These findings should be considered when patients decide whether to receive adjuvant chemotherapy, particularly when expected benefit is low. PMID:24777606

Adjuvant chemotherapy in older women (ACTION) study – what did we learn from the pilot phase?

PubMed Central

Leonard, R; Ballinger, R; Cameron, D; Ellis, P; Fallowfield, L; Gosney, M; Johnson, L; Kilburn, L S; Makris, A; Mansi, J; Reed, M; Ring, A; Robinson, A; Simmonds, P; Thomas, G; Bliss, J M

2011-01-01

Background: The ACTION trial was initiated to provide evidence from a randomised trial on the effects of chemotherapy in women aged over 70 years where evidence for risk and benefit are lacking. Methods: This was a randomised, phase III clinical trial for high risk, oestrogen receptor (ER) negative/ER weakly positive early breast cancer. The trial planned to recruit 1000 women aged 70 years and older, randomised to receive 4 cycles of anthracycline chemotherapy or observation. The primary endpoint was relapse-free interval. The trial included a pilot phase to assess the acceptability and feasibility of recruitment. Results: The trial opened at 43 UK centres. Information on number of patients approached was available from 38 centres. Of the 43 eligible patients that were approached, 39 were not randomised due to patients declining entry. After 10 months only 4 patients had been randomised and after discussion with the research funder, the trial was closed and funding terminated. Conclusion: Despite widespread support at several public meetings, input from patient groups including representation on the Trial Management Group, the trial failed to recruit due to the inability to convince patients to accept randomisation. It would therefore seem that randomising the patients to receive chemotherapy vs observation is not a viable design in the current era for this patient population. PMID:21989185

A prospective cohort study of the effects of adjuvant breast cancer chemotherapy on taste function, food liking, appetite and associated nutritional outcomes.

PubMed

Boltong, Anna; Aranda, Sanchia; Keast, Russell; Wynne, Rochelle; Francis, Prudence A; Chirgwin, Jacqueline; Gough, Karla

2014-01-01

'Taste' changes are commonly reported during chemotherapy. It is unclear to what extent this relates to actual changes in taste function or to changes in appetite and food liking and how these changes affect dietary intake and nutritional status. This prospective, repeated measures cohort study recruited participants from three oncology clinics. Women (n = 52) prescribed adjuvant chemotherapy underwent standardised testing of taste perception, appetite and food liking at six time points to measure change from baseline. Associations between taste and hedonic changes and nutritional outcomes were examined. Taste function was significantly reduced early in chemotherapy cycles (p<0.05) but showed recovery by late in the cycle. Ability to correctly identify salty, sour and umami tastants was reduced. Liking of sweet food decreased early and mid-cycle (p<0.01) but not late cycle. Liking of savory food was not significantly affected. Appetite decreased early in the cycle (p<0.001). Reduced taste function was associated with lowest kilojoule intake (r = 0.31; p = 0.008) as was appetite loss with reduced kilojoule (r = 0.34; p = 0.002) and protein intake (r = 0.36; p = 0.001) early in the third chemotherapy cycle. Decreased appetite early in the third and final chemotherapy cycles was associated with a decline in BMI (p = <0.0005) over the study period. Resolution of taste function, food liking and appetite was observed 8 weeks after chemotherapy completion. There was no association between taste change and dry mouth, oral mucositis or nausea. The results reveal, for the first time, the cyclical yet transient effects of adjuvant chemotherapy on taste function and the link between taste and hedonic changes, dietary intake and nutritional outcomes. The results should be used to inform reliable pre-chemotherapy education.

Exploring the Feasibility of a Broad-Reach Physical Activity Behavior Change Intervention for Women Receiving Chemotherapy for Breast Cancer: A Randomized Trial.

PubMed

Vallance, Jeff K; Friedenreich, Christine M; Lavallee, Celeste M; Culos-Reed, Nicole; Mackey, John R; Walley, Barbara; Courneya, Kerry S

2016-02-01

Facilitating healthy levels of physical activity (PA) during chemotherapy is important for the psychosocial and physical health of breast cancer survivors. The primary objective of this feasibility study was to examine the effects of a broad-reach PA behavior change intervention among women with breast cancer receiving adjuvant chemotherapy. Breast cancer patients receiving adjuvant chemotherapy (N = 95) were randomly assigned to receive a PA resource kit consisting of tailored print materials and a step pedometer (intervention) or a standard public health PA recommendation (standard recommendation). The primary outcome was daily pedometer steps. Secondary outcomes were self-reported light, moderate, and vigorous intensity PA, total moderate-to-vigorous PA, and sedentary time. Assessments were conducted before and after adjuvant chemotherapy. Attrition was 19% (17 of 95). Intervention patients wore their step pedometer for 85 days (range, 35-144 days; SD = 26.4) for a 95% adherence rate. Analyses of covariance suggested that the intervention was not statistically superior to standard recommendation for daily average pedometer steps (-771; 95% CI = -2024 to 482; P = 0.22), total MVPA minutes (-4; 95% CI = -62 to 570; P = 0.90), or sedentary time (+160; 95% CI = -186 to 506; P = 0.42). This broach-reach and low intensive intervention was not more effective for promoting PA in breast cancer patients receiving chemotherapy than providing the standard public health guidelines for PA. Achieving physical activity behavior change during adjuvant breast cancer chemotherapy may require some level of supervised physical activity or more intensive (e.g., face-to-face, supervised) interventions. ©2015 American Association for Cancer Research.

Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control.

PubMed

Glynne-Jones, R; Counsell, N; Quirke, P; Mortensen, N; Maraveyas, A; Meadows, H M; Ledermann, J; Sebag-Montefiore, D

2014-07-01

In stage III colon cancer, oxaliplatin/5-fluorouracil (5-FU)-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy. Eligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or six cycles of XELOX. The primary end point was DFS; secondary end points were acute toxicity and OS. 390 patients were required in each arm, to detect an improvement in 3-year DFS from 40% to 50.5%, with 85% power and two-sided 5% significance level. The study closed prematurely in 2008 because of poor accrual. Only 113 patients were randomly assigned to either observation (n = 59) or XELOX (n = 54). Compliance was poor, 93% allocated chemotherapy started and 48% completed six cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 toxicity 40%. After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm had relapsed or died compared with 12 patients (22%) in XELOX. The 3-year DFS rate was 78% with XELOX and 71% with observation [hazard ratio (HR) for DFS = 0.80; 95% confidence interval (CI) 0.38-1.69; P = 0.56]. The 3-year OS for XELOX and observation were 89% and 88%, respectively (HR for OS = 1.18; 95% CI 0.43-3.26; P = 0.75). The observed improvement in DFS for adjuvant XELOX and similar OS were not statistically significant, as expected given the small number of patients and consequent low power. Our findings support the need for trials that test the role of neoadjuvant chemotherapy. NCT00427713. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.

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 includedmore » 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.« less

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

PubMed

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed

Lawrence, J A; 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

2016-02-01

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. 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. 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. Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. 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.

Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy.

PubMed

Silverman, Daniel H S; Dy, Christine J; Castellon, Steven A; Lai, Jasmine; Pio, Betty S; Abraham, Laura; Waddell, Kari; Petersen, Laura; Phelps, Michael E; Ganz, Patricia A

2007-07-01

To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer. Subjects treated for breast cancer with adjuvant chemotherapy remotely (5-10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis. During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects. Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5-10 years after completion of chemotherapy.

Survival benefit of neoadjuvant chemotherapy for resectable breast cancer: A meta-analysis.

PubMed

Chen, Yan; Shi, Xiu-E; Tian, Jin-Hui; Yang, Xu-Juan; Wang, Yong-Feng; Yang, Ke-Hu

2018-05-01

Neoadjuvant chemotherapy (NAC) increases breast conservation rates in patients with resectable breast cancer at the associated cost of higher locoregional recurrence rates; however, the magnitude of the survival benefits of NAC for these patients remains undefined. Therefore, we aimed to clarify the survival benefit of NAC versus postoperative chemotherapy by conducting an updated meta-analysis of randomized clinical trials (RCTs). The authors searched the Cochrane Library, PubMed, Embase, Web of Science, Chinese biomedical literature database, and Chinese Scientific Journals full-text database from their inception to December 2016. The authors identified relevant RCTs that compared NAC with postoperative chemotherapy in the treatment of operable breast cancer. The main endpoints were overall survival (OS) and recurrence-free survival (RFS). A total of 21 citations representing 16 unique studies were eligible. There were 787 deaths among 2794 patients assigned to NAC groups and 816 deaths among 2799 patients assigned to adjuvant chemotherapy groups. A meta-analysis of data indicated that there was no significant benefit in terms of OS ([hazard ratio [HR] = 1.03, 95% confidence interval [CI]: 0.94-1.13, P = .51) and RFS (HR = 1.01, 95% CI: 0.93-1.10, P = .80) between the NAC and postoperative chemotherapy groups. The pooled HR estimate for OS was not influenced by NAC cycles, the total number of chemotherapy cycles, administration of tamoxifen, administration of adjuvant chemotherapy, or type of NAC regimen. Subgroup analysis showed that the pooled HR estimate for RFS was influenced by anthracycline-containing regimens. Patients with a pathological complete response had superior survival outcomes compared with patients who had residual disease. The survival benefits for patients with operable breast cancer who received either NAC or adjuvant chemotherapy based on anthracycline regimens were comparable.

Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.

PubMed

Neoptolemos, John P; Stocken, Deborah D; Bassi, Claudio; Ghaneh, Paula; Cunningham, David; Goldstein, David; Padbury, Robert; Moore, Malcolm J; Gallinger, Steven; Mariette, Christophe; Wente, Moritz N; Izbicki, Jakob R; Friess, Helmut; Lerch, Markus M; Dervenis, Christos; Oláh, Attila; Butturini, Giovanni; Doi, Ryuichiro; Lind, Pehr A; Smith, David; Valle, Juan W; Palmer, Daniel H; Buckels, John A; Thompson, Joyce; McKay, Colin J; Rawcliffe, Charlotte L; Büchler, Markus W

2010-09-08

Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer. The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up. Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months. Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life. Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

PubMed

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial.

PubMed

Del Mastro, Lucia; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Olmeo, Nina; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Pronzato, Paolo; Bighin, Claudia; Levaggi, Alessia; Giraudi, Sara; Cresti, Nicola; Magnolfi, Emanuela; Scotto, Tiziana; Vecchio, Carlo; Venturini, Marco

2011-07-20

Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available. To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy. The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data. Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy. Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy). The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last

Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001-2012).

PubMed

Wendelburg, Kristin M; Price, Lori Lyn; Burgess, Kristine E; Lyons, Jeremiah A; Lew, Felicia H; Berg, John

2015-08-15

To determine survival time for dogs with splenic hemangiosarcoma treated with splenectomy alone, identify potential prognostic factors, and evaluate the efficacy of adjuvant chemotherapy. Retrospective case series. 208 dogs. Medical records were reviewed, long-term follow-up information was obtained, and survival data were analyzed statistically. 154 dogs were treated with surgery alone, and 54 were treated with surgery and chemotherapy. Twenty-eight dogs received conventional chemotherapy, 13 received cyclophosphamide-based metronomic chemotherapy, and 13 received both conventional and metronomic chemotherapy. Median survival time of dogs treated with splenectomy alone was 1.6 months. Clinical stage was the only prognostic factor significantly associated with survival time. When the entire follow-up period was considered, there was no significant difference in survival time between dogs treated with surgery alone and dogs treated with surgery and chemotherapy. However, during the first 4 months of follow-up, after adjusting for the effects of clinical stage, survival time was significantly prolonged among dogs receiving any type of chemotherapy (hazard ratio, 0.6) and among dogs receiving both conventional and metronomic chemotherapy (hazard ratio, 0.4). Clinical stage was strongly associated with prognosis for dogs with splenic hemangiosarcoma. Chemotherapy was effective in prolonging survival time during the early portion of the follow-up period. Combinations of doxorubicin-based conventional protocols and cyclophosphamide-based metronomic protocols appeared to be more effective than either type of chemotherapy alone, but prolongations in survival time resulting from current protocols were modest.

Rethinking exercise identity: a qualitative study of physically inactive cancer patients’ transforming process while undergoing chemotherapy

PubMed Central

Adamsen, Lis; Andersen, Christina; Lillelund, Christian; Bloomquist, Kira; Møller, Tom

2017-01-01

Objective To explore physically inactive breast and colon cancer patients’ prediagnosis exercise history and attitudes to physical activity (PA) and experiences in initiating PA while undergoing adjuvant chemotherapy. Design An explorative qualitative study guided the interpretive analysis of semistructured, open-ended interviews conducted at initiation of chemotherapy and after 12 weeks. The study was embedded in a pilot randomised controlled trial. Setting Participants were recruited from the Oncological Department at a hospital in Copenhagen, Denmark. Participants 33 patients with cancer, median age 49 years: 25 patients with breast cancer and 8 with colon cancer, 72% with a low cardiac respiratory fitness level and the majority with a high level of education. Patients received adjuvant chemotherapy, oncologist’s PA recommendation and exercise, cancer nurse specialist’s counselling prior to allocation to PA interventions or waitlist control group. Results Prediagnosis exercise had been excluded from patients’ daily lives due to perceptions of exercise as boring, lack of discipline and stressful work conditions for both genders. Recommendations from oncologists and nurses inspired the patients to reconsider their attitudes and behaviour by accepting recruitment and participation in PA interventions during chemotherapy. Despite extensive side effects, most patients adhered to their PA commitment due to their perception of the bodily, emotional and social benefits and support of healthcare professionals, peers and family. Conclusion The patients’ attitude towards exercise transformed from having no priority in patients’ daily lives prediagnosis to being highly prioritised. This study identified four important phases in the exercise transformation process during the patients’ treatment trajectory of relevance to clinicians in identifying, motivating and supporting physically inactive patients with cancer at long-term risk. Clinicians should address

Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials.

PubMed

Yerushalmi, R; Dong, B; Chapman, J W; Goss, P E; Pollak, M N; Burnell, M J; Levine, M N; Bramwell, V H C; Pritchard, K I; Whelan, T J; Ingle, J N; Shepherd, L E; Parulekar, W R; Han, L; Ding, K; Gelmon, K A

2017-07-01

We hypothesized that increased baseline BMI and BMI change would negatively impact clinical outcomes with adjuvant breast cancer systemic therapy. Data from chemotherapy trials MA.5 and MA.21; endocrine therapy MA.12, MA.14 and MA.27; and trastuzumab HERA/MA.24 were analyzed. The primary objective was to examine the effect of BMI change on breast cancer-free interval (BCFI) landmarked at 5 years; secondary objectives included BMI changes at 1 and 3 years; BMI changes on disease-specific survival (DSS) and overall survival (OS); and effects of baseline BMI. Stratified analyses included trial therapy and composite trial stratification factors. In pre-/peri-/early post-menopausal chemotherapy trials (N = 2793), baseline BMI did not impact any endpoint and increased BMI from baseline did not significantly affect BCFI (P = 0.85) after 5 years although it was associated with worse BCFI (P = 0.03) and DSS (P = 0.07) after 1 year. BMI increase by 3 and 5 years was associated with better DSS (P = 0.01; 0.01) and OS (P = 0.003; 0.05). In pre-menopausal endocrine therapy trial MA.12 (N = 672), patients with higher baseline BMI had worse BCFI (P = 0.02) after 1 year, worse DSS (P = 0.05; 0.004) after 1 and 5 years and worse OS (P = 0.01) after 5 years. Increased BMI did not impact BCFI (P = 0.90) after 5 years, although it was associated with worse BCFI (P = 0.01) after 1 year. In post-menopausal endocrine therapy trials MA.14 and MA.27 (N = 8236), baseline BMI did not significantly impact outcome for any endpoint. BMI change did not impact BCFI or DSS after 1 or 3 years, although a mean increased BMI of 0.3 was associated with better OS (P = 0.02) after 1 year. With the administration of trastuzumab (N = 1395) baseline BMI and BMI change did not significantly impact outcomes. Higher baseline BMI and BMI increases negatively affected outcomes only in pre-/peri-/early post-menopausal trial patients. Otherwise, BMI

Metronomic chemotherapy.

PubMed

Mutsaers, Anthony J

2009-08-01

Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

PubMed

Wang, Xiaojie; Zheng, Hong; Shou, Tao; Tang, Chunming; Miao, Kun; Wang, Ping

2017-03-29

Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. We searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords "osteosarcoma", "osteogenic sarcoma", "chemotherapy", and "random*" without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons. We included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen. We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine

Planned Safety Analysis of the ACTS-CC 02 Trial: A Randomized Phase III Trial of S-1 With Oxaliplatin Versus Tegafur and Uracil With Leucovorin as Adjuvant Chemotherapy for High-Risk Stage III Colon Cancer.

PubMed

Kusumoto, Tetsuya; Sunami, Eiji; Ota, Mitsuyoshi; Yoshida, Kazuhiro; Sakamoto, Yoshiyuki; Tomita, Naohiro; Maeda, Atsuyuki; Mochizuki, Izumi; Okabe, Michio; Kunieda, Katsuyuki; Yamauchi, Junichiro; Itabashi, Michio; Kotake, Kenjiro; Takahashi, Keiichi; Baba, Hideo; Boku, Narikazu; Aiba, Keisuke; Ishiguro, Megumi; Morita, Satoshi; Sugihara, Kenichi

2018-06-01

This trial was designed to verify the superiority of 6 months of postoperative adjuvant chemotherapy with SOX (S-1 with oxaliplatin) with UFT (tegafur and uracil) with LV (leucovorin) in terms of disease-free survival in patients with high-risk stage III colon cancer. We report the results of a planned safety analysis. Patients who underwent curative resection for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries) were randomly assigned to receive either UFT/LV (300-600 mg/d UFT with 75 mg/d LV on days 1-28, every 35 days, for 5 cycles) or SOX (100 mg/m 2 of oxaliplatin on day 1 with 80-120 mg/d S-1 on days 1-14, every 21 days, for 8 cycles). Treatment status and safety were evaluated. A total of 966 patients were enrolled, and 932 patients were included in safety analyses. The planned 6-month protocol treatment was received by 76.9% of the patients in the UFT/LV group and 65.8% of those in the SOX group. The overall incidence of any Grade adverse events (AEs) were 91.3% in the UFT/LV group and 98.7% in the SOX group, and those of Grade ≥ 3 AEs were 16.1% and 36.1%, respectively. As for Grade ≥ 3 AEs, leukopenia, neutropenia, thrombocytopenia, and sensory neuropathy were more common in the SOX group. The incidence of Grade ≥ 3 sensory peripheral neuropathy was 4.6% in the SOX group. The completion rate of adjuvant SOX and its incidence of AEs were acceptable in patients with colon cancer. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

PubMed Central

2011-01-01

Background To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Methods Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. Results From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. Conclusions In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. Trial registration ClinicalTrials.gov NCT00540800. PMID:21324184

Tumor-infiltrating neutrophils predict benefit from adjuvant chemotherapy in patients with muscle invasive bladder cancer.

PubMed

Zhou, Lin; Xu, Le; Chen, Lingli; Fu, Qiang; Liu, Zheng; Chang, Yuan; Lin, Zongming; Xu, Jiejie

2017-01-01

Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in tumorigenesis. The objective of this study is to assess the prognostic effect of TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the study. TINs were evaluated by immunohistochemical staining of CD66b or the CIBERSORT method. Patients with high TINs had a significantly poorer overall survival ( p = 0.001, p < 0.001, and p = 0.002, respectively) in the three sets. In the multivariate analysis, the presence of high TINs (HR = 2.122, p = 0.007; HR = 3.807, p < 0.001; HR = 2.104, p = 0.001; respectively) was identified as an independent prognostic factor for overall survival in the three sets. More importantly, Low TINs patients had significantly longer overall survival in patients without ACT in the three sets. Gene set enrichment analysis showed that lymphocyte activation ( p < 0.001) and T cell activation ( p = 0.008) were significantly enriched in the low TINs group. In addition, TINs were negatively correlated with CD8 + T cells, suggesting that the status of high-TINs was linked to the status of immunosuppression in MIBC. TINs could be used as independent prognostic factor. Low TINs identified a subgroup of MIBC patients who appeared to benefit from adjuvant chemotherapy. Incorporation of TINs into TNM system could further stratify patients with different prognosis.

Tumor-infiltrating neutrophils predict benefit from adjuvant chemotherapy in patients with muscle invasive bladder cancer

PubMed Central

Zhou, Lin; Xu, Le; Chen, Lingli; Fu, Qiang; Liu, Zheng; Chang, Yuan; Lin, Zongming; Xu, Jiejie

2017-01-01

ABSTRACT Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in tumorigenesis. The objective of this study is to assess the prognostic effect of TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the study. TINs were evaluated by immunohistochemical staining of CD66b or the CIBERSORT method. Patients with high TINs had a significantly poorer overall survival (p = 0.001, p < 0.001, and p = 0.002, respectively) in the three sets. In the multivariate analysis, the presence of high TINs (HR = 2.122, p = 0.007; HR = 3.807, p < 0.001; HR = 2.104, p = 0.001; respectively) was identified as an independent prognostic factor for overall survival in the three sets. More importantly, Low TINs patients had significantly longer overall survival in patients without ACT in the three sets. Gene set enrichment analysis showed that lymphocyte activation (p < 0.001) and T cell activation (p = 0.008) were significantly enriched in the low TINs group. In addition, TINs were negatively correlated with CD8+ T cells, suggesting that the status of high-TINs was linked to the status of immunosuppression in MIBC. TINs could be used as independent prognostic factor. Low TINs identified a subgroup of MIBC patients who appeared to benefit from adjuvant chemotherapy. Incorporation of TINs into TNM system could further stratify patients with different prognosis. PMID:28507798

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

PubMed

Inoue, Takuya; Takagi, Hironori; Owada, Yuki; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Yokouchi, Hiroshi; Kanazawa, Kenya; Ohbuchi, Katsuya; Fukushima, Takahisa; Munakata, Mitsuru; Suzuki, Hiroyuki

2017-10-18

Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.

PubMed

Davies, C; Godwin, J; Gray, R; Clarke, M; Cutter, D; Darby, S; McGale, P; Pan, H C; Taylor, C; Wang, Y C; Dowsett, M; Ingle, J; Peto, R

2011-08-27

As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21,457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. In oestrogen receptor (ER)-positive disease (n=10,645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0-4 and RR 0·68 [0·06] during years 5-9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10-14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10-19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0-4, 0·66 [0·05] during years 5-9, and 0·68 [0·08] during years 10-14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional

Adjuvant leuprolide with or without docetaxel in patients with high-risk prostate cancer after radical prostatectomy (TAX-3501): important lessons for future trials.

PubMed

Schweizer, Michael T; Huang, Peng; Kattan, Michael W; Kibel, Adam S; de Wit, Ronald; Sternberg, Cora N; Epstein, Jonathan I; Eisenberger, Mario A

2013-10-15

The current trial evaluated 2 common therapies for patients with advanced prostate cancer, docetaxel and hormonal therapy (HT), in the surgical adjuvant setting. TAX-3501 was a randomized, phase 3, adjuvant study post-radical prostatectomy (RP) in high-risk patients with prostate cancer (n=228) comparing 18 months of HT with (CHT) without docetaxel chemotherapy either immediately (I) or deferred (D). High-risk disease was defined as a 5-year freedom-from-disease-progression rate of ≤ 60% as predicted by a post-RP nomogram. Progression-free survival (PFS), including prostate-specific antigen disease recurrence, was the primary endpoint. The authors also assessed the accuracy of the nomogram and analyzed testosterone recovery in 108 patients treated with HT who had at least 1 posttreatment testosterone value. Between December 2005 and September 2007, 228 patients were randomized between the treatment cohorts. TAX-3501 was terminated prematurely because of enrollment challenges, leaving it underpowered to detect differences in PFS. After a median follow-up of 3.4 years (interquartile range, 2.3-3.8 years), 39 of 228 patients (17%) demonstrated PSA disease progression, and metastatic disease progression occurred in 1 patient. The median time to baseline testosterone recovery after the completion of treatment was prolonged at 487 days (95% confidence interval, 457-546 days). The nomogram's predicted versus observed freedom from disease progression was significantly different for the combination D(HT) and D(CHT) group (P<.00001). TAX-3501 illustrated several difficulties involved in conducting postoperative adjuvant systemic trials in men with high-risk prostate cancer: the lack of consensus regarding patient selection and treatment, the need for long follow-up time, nonvalidated intermediate endpoints, evolving standard approaches, and the need for long-term research support. Except for selected patients at very high-risk of disease recurrence and death, surgical

Adjuvant treatment for endometrial cancer: literature review and recommendations by the Comité de l'évolution des pratiques en oncologie (CEPO).

PubMed

Morneau, Mélanie; Foster, William; Lalancette, Marc; Van Nguyen-Huynh, Thu; Renaud, Marie-Claude; Samouëlian, Vanessa; Letarte, Nathalie; Almanric, Karine; Boily, Gino; Bouchard, Philippe; Boulanger, Jim; Cournoyer, Ghislain; Couture, Félix; Gervais, Normand; Goulet, Stéphanie; Guay, Marie-Pascale; Kavanagh, Mélanie; Lemieux, Julie; Lespérance, Bernard; Letarte, Nathalie; Morneau, Mélanie; Ouellet, Jean-François; Pineau, Gilles; Rajan, Raghu; Roy, Isabelle; Samson, Benoît; Sidéris, Lucas; Vincent, François

2013-10-01

Despite the very good prognosis of endometrial cancer, a number of patients with localized disease relapse following surgery. Therefore, various adjuvant therapeutic approaches have been studied. The objective of this review is to evaluate the efficacy and safety of neoadjuvant and adjuvant therapies in patients with resectable endometrial cancer and to develop evidence-based recommendations. A review of the scientific literature published between January 1990 and June 2012 was performed. The search was limited to published phase III clinical trials and meta-analyses evaluating the efficacy of neoadjuvant or adjuvant therapies in patients with endometrial carcinoma or carcinosarcoma. A total of 23 studies and five meta-analyses were identified. The selected literature showed that in patients with a low risk of recurrence, post-surgical observation is safe and recommended in most cases. There are several therapeutic modalities available for treatment of endometrial cancers with higher risk of recurrence, including vaginal brachytherapy, external beam radiotherapy, chemotherapy, or a combination of these. Considering the evidence available to date, the CEPO recommends the following: (1)post-surgical observation for most patients with a low recurrence risk; (2)adjuvant vaginal brachytherapy for patients with an intermediate recurrence risk; (3)adjuvant pelvic radiotherapy with or without vaginal brachytherapy for patients with a high recurrence risk; addition of adjuvant chemotherapy may be considered as an option for selected patients (excellent functional status, no significant co-morbidities, poor prognostic factors); (4)adjuvant chemotherapy and pelvic radiotherapy with or without brachytherapy and para-aortic irradiation for patients with advanced disease; © 2013.

Statistical monitoring of data quality and consistency in the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial.

PubMed

Timmermans, Catherine; Doffagne, Erik; Venet, David; Desmet, Lieven; Legrand, Catherine; Burzykowski, Tomasz; Buyse, Marc

2016-01-01

Data quality may impact the outcome of clinical trials; hence, there is a need to implement quality control strategies for the data collected. Traditional approaches to quality control have primarily used source data verification during on-site monitoring visits, but these approaches are hugely expensive as well as ineffective. There is growing interest in central statistical monitoring (CSM) as an effective way to ensure data quality and consistency in multicenter clinical trials. CSM with SMART™ uses advanced statistical tools that help identify centers with atypical data patterns which might be the sign of an underlying quality issue. This approach was used to assess the quality and consistency of the data collected in the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial, involving 1495 patients across 232 centers in Japan. In the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial, very few atypical data patterns were found among the participating centers, and none of these patterns were deemed to be related to a quality issue that could significantly affect the outcome of the trial. CSM can be used to provide a check of the quality of the data from completed multicenter clinical trials before analysis, publication, and submission of the results to regulatory agencies. It can also form the basis of a risk-based monitoring strategy in ongoing multicenter trials. CSM aims at improving data quality in clinical trials while also reducing monitoring costs.

Chemotherapy in Old Women with Breast Cancer: Is Age Still a Predictor for Under Treatment?

PubMed

Meresse, Mégane; Bouhnik, Anne-Déborah; Bendiane, Marc-Karim; Retornaz, Frédérique; Rousseau, Frédérique; Rey, Dominique; Giorgi, Roch

2017-05-01

Breast cancer affects mostly older women but there are no guidelines especially devoted to adjuvant chemotherapy for this population. In this context, this study was carried out in a population-based cohort of French elderly women with breast cancer, to check adherence to the existing national guidelines according to the women's age, taking into account the evolution of the situation over time for women requiring chemotherapy. Between October 2006 and December 2008, all consecutive women included in the French Health registry for a biopsy-proven primary nonmetastatic breast cancer, aged 65-80 years at diagnosis, and living in South Eastern France, were asked to participate in a cohort study. Medical information was collected from physicians. The study population was restricted to the 223 women who were recommended adjuvant chemotherapy according to national guidelines. Those who received chemotherapy were compared to those who did not receive this treatment. Among these 223 women 55% had received chemotherapy. Only three women refused the treatment. Less than 8% have had a geriatric assessment before treatment decision and only two were proposed to participate in a clinical trial. After adjustment for comorbidity score, tumor characteristics, socio-demographic characteristics, and year of diagnosis, increasing patient age was independently associated with decreased guideline concordance for adjuvant chemotherapy. Women aged 75-80 years received chemotherapy more than four times less often than women aged 65-74 years. However, the percentage of women who received chemotherapy increased from 33% to 58% between 2006 and 2008, in parallel with the setting up of Onco-Geriatric Coordination Units in the area. In France, chronological age remains a barrier to receive chemotherapy for older breast cancer women but the establishment of a formal collaboration between oncologists and geriatricians seems to be an effective way to improve care delivery in this population. �

The Use of a Cognitive Protectant to Help Maintain Quality of Life and Cognition in Premenopausal Women with Breast Cancer Undergoing Adjuvant Chemotherapy

DTIC Science & Technology

2005-10-01

quality of life and cognitive function are experienced by women with breast cancer who are receiving adjuvant chemotherapy. These decrements can be identified in some women even several years following treatment. The majority of relevant research has been based on retrospective data in women with breast cancer. Current estimates suggest that 25% of breast cancers will be diagnosed in women under age 50, yet very little data are available regarding younger women’s cognitive function and quality of life during chemotherapy.

Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

PubMed

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

2015-02-01

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). 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. 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. 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. © 2014 by American Society of Clinical Oncology.

Feasibility study of a randomized controlled trial of a telephone-delivered problem-solving-occupational therapy intervention to reduce participation restrictions in rural breast cancer survivors undergoing chemotherapy.

PubMed

Hegel, Mark T; Lyons, Kathleen D; Hull, Jay G; Kaufman, Peter; Urquhart, Laura; Li, Zhongze; Ahles, Tim A

2011-10-01

Breast cancer patients receiving adjuvant chemotherapy often experience functional effects of treatment that limit participation in life activities. The purpose of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) of a novel intervention for these restrictions, determine acceptability of the intervention, and preliminarily assess its effects. A pilot RCT of a telephone-delivered Problem-solving and Occupational Therapy intervention (PST-OT) to improve participation restrictions in rural breast cancer patients undergoing chemotherapy. Thirty-one participants with Stages 1-3 breast cancer were randomized to 6 weekly sessions of PST-OT (n = 15) and usual care (n = 16). The primary study outcome was the feasibility of conducting the trial. Secondary outcomes were functional, quality of life and emotional status as assessed at baseline, 6 and 12 weeks. Of 46 patients referred 31 were enrolled (67% recruitment rate), of which 6 participants withdrew (81% retention rate). Twenty-four participants completed all study-related assessments (77%). Ninety-two percent of PST-OT participants were highly satisfied with the intervention, and 92% reported PST-OT to be helpful/very helpful for overcoming participation restrictions. Ninety-seven percent of planned PST-OT treatment sessions were completed. Completion rates for PST-OT homework tasks were high. Measures of functioning, quality of life, and emotional state favored the PST-OT condition. This pilot study suggests that an RCT of the PST-OT intervention is feasible to conduct with rural breast cancer patients undergoing adjuvant chemotherapy and that PST-OT may have positive effects on function, quality of life, and emotional state. 2010 John Wiley & Sons, Ltd.

Evaluation of the Effectiveness of a Multimodal Complementary Medicine Program for Improving the Quality of Life of Cancer Patients during Adjuvant Radiotherapy and/or Chemotherapy or Outpatient Aftercare.

PubMed

Domnick, Martin; Domnick, Manju; Wiebelitz, Karl-Rüdiger; Beer, André-Michael

2017-01-01

Evidence for complementary therapies as important strategies to relieve cancer treatment-associated symptoms is increasing. Mostly, these complementary therapies start at the end of adjuvant treatments, resulting in a long delay until the well-being of patients is addressed. Further, long distances between the rehabilitation center and the patients' residence hinder patients' compliance. The multimodal outpatient LOTUS Care Cure Project (LCCP) was tested in a randomized controlled trial including patients of various cancer entities and stages while on adjuvant chemotherapy and/or radiotherapy or outpatient aftercare. The intervention group received the LCCP additionally to the conventional treatment (LCCP group, n = 50). The control group (CG) was split into 2 groups, with (CG1, n = 33) and without (CG2, n = 17) weekly talks. The primary endpoint was quality of life (QoL) after 3 months. In the LCCP group, QoL significantly improved after 3 months compared to CG2 (p = 0.022) but not compared to CG1. Other parameters showing a significant improvement were cognitive (p < 0.05, vs. CG1 and CG2) and social function (p < 0.05, vs. CG2). This pilot study describes a multimodal outpatient complementary therapy program conducted in parallel with conventional therapies and its potential to significantly improve QoL and reduce treatment-associated side effects. To substantiate these data, multicenter trials are needed. © 2017 S. Karger AG, Basel.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

PubMed

Jin, Zhaohui; Hartgers, Mindy L; Sanhueza, Cristobal T; Shubert, Christopher R; Alberts, Steven R; Truty, Mark J; Muppa, Prasuna; Nagorney, David M; Smyrk, Thomas C; Hassan, Mohamed; Mahipal, Amit

2018-05-01

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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

PubMed

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

2015-09-01

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. 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. 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. 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.

[Indication of chemotherapy according to histological type of musculoskeletal sarcomas].

PubMed

Goto, Takahiro; Okuma, Tomotake; Ogura, Koichi; Imanishi, Jungo; Hozumi, Takahiro; Kondo, Taiji

2009-02-01

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. As the efficacy of chemotherapy varies according to the histological type of sarcoma, its indication is determined according to the histological type and the stage. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy, so it is absolutely necessary. Drugs commonly used for osteosarcoma include adriamycin, cisplatin, methotrexate, vincristine, and ifosfamide. For Ewing's sarcoma and rhabdomyosarcoma, vincristine, actinomycin-D, cyclophosphamide, etoposide, and ifosfamide are commonly used. On the other hand, the efficacy of chemotherapy is unclear in most of the non-round cell sarcomas, e. g., malignant fibrous histiocytoma, pleomorphic liposarcoma, and leiomyosarcoma, so adjuvant chemotherapy is relatively indicated and often performed preoperatively. The efficacy is evaluated by reduction of the tumor volume as a surrogate marker. Postoperative chemotherapy is performed when the preoperative chemotherapy is effective. Nowadays, several kinds of antitumor agents are usually used for non-round cell sarcomas, and many authors have reported various kinds of regimens and their clinical results. Among them, the key drugs are adriamycin and ifosfamide. Recently, taxanes and gemcitabine are sometimes used. For chemoresistant sarcomas, e. g., chondrosarcoma, chordoma, alveolar soft part sarcoma, chemotherapy is rarely indicated, even if the tumor is histologically high grade and large. Low-grade musculoskeletal sarcomas, e. g., low-grade chondrosarcoma, central low-grade osteosarcoma, parosteal osteosarcoma, well-differentiated liposarcoma, and dermatofibrosarcoma protuberans, are well cured only by surgical excision, and adjuvant chemotherapy is therefore not indicated. Superficially

Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Robert C.; Iott, Matthew J.; Corsini, Michele M.

2009-10-01

Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28more » fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.« less

Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

PubMed

Perrone, F; Nuzzo, F; Di Rella, F; Gravina, A; Iodice, G; Labonia, V; Landi, G; Pacilio, C; Rossi, E; De Laurentiis, M; D'Aiuto, M; Botti, G; Forestieri, V; Lauria, R; De Placido, S; Tinessa, V; Daniele, B; Gori, S; Colantuoni, G; Barni, S; Riccardi, F; De Maio, E; Montanino, A; Morabito, A; Daniele, G; Di Maio, M; Piccirillo, M C; Signoriello, S; Gallo, C; de Matteis, A

2015-04-01

Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. NCT00331097

Comparison of capecitabine and oxaliplatin with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy.

PubMed

Cho, Jang Ho; Lim, Jae Yun; Cho, Jae Yong

2017-01-01

To compare capecitabine and oxaliplatin (XELOX) with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy. Clinical data from 206 patients who received XELOX or S-1 regimens as adjuvant chemotherapy in stage III gastric cancer were collected. Patients were divided into 2 groups according to regimen; the groups were XELOX (n = 114) and S-1 monotherapy (n = 92). 3-year disease-free survival (DFS) was higher in the S-1 group than in the XELOX group (66.6% vs 59.1%; p = 0.636). 3-year overall survival (OS) was 75.6% in the S-1 group and 69.6% in the XELOX group (p = 0.495). But, the difference was not statistically significant. Especially, for patients with stage IIIC disease, 3-year overall survival was 55.2% in the XELOX group and 39.0% in the S-1 group (hazard ratio, HR 0.50, 95% confidence interval, CI 0.23-1.10; p = 0.075). In multivariate analysis, N stage (HR, 5.639; 95% CI, 1.297-24.522; p = 0.021) and cycle completion as planned (HR, 5.734; 95% CI, 3.007-10.936; p<0.001) were independent predictors of overall survival. Adjuvant XELOX and S-1 regimen did not prove anything superior for stage III gastric cancer in this study. But, XELOX had a tendency to be superior to S-1 in stage IIIC gastric cancer after D2 gastrectomy although the difference was not statistically significant. N stage and cycle completion as planned were prognostic factors.

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

PubMed

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Predictive test for chemotherapy response in resectable gastric cancer: a multi-cohort, retrospective analysis.

PubMed

Cheong, Jae-Ho; Yang, Han-Kwang; Kim, Hyunki; Kim, Woo Ho; Kim, Young-Woo; Kook, Myeong-Cherl; Park, Young-Kyu; Kim, Hyung-Ho; Lee, Hye Seung; Lee, Kyung Hee; Gu, Mi Jin; Kim, Ha Yan; Lee, Jinae; Choi, Seung Ho; Hong, Soonwon; Kim, Jong Won; Choi, Yoon Young; Hyung, Woo Jin; Jang, Eunji; Kim, Hyeseon; Huh, Yong-Min; Noh, Sung Hoon

2018-05-01

Adjuvant chemotherapy after surgery improves survival of patients with stage II-III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II-III gastric cancer. In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II-III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival. We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625

Adjuvant chemotherapy with 5-fluorouracil, L-folinic acid and levamisole for patients with colorectal cancer: non-randomised comparison of weekly versus four-weekly schedules--less pain, same gain. QUASAR Colorectal Cancer Study Group.

PubMed

Kerr, D J; Gray, R; McConkey, C; Barnwell, J

2000-08-01

QUASAR is a large trial of adjuvant chemotherapy for colorectal cancer in which clinicians could choose to deliver a standard adjuvant cytotoxic chemotherapy regimen, 5-fluorouracil (5-FU) and L-folinic acid (L-FA), in either a once-weekly or a four-weekly schedule. We report results of a non-randomised comparison between these schedules with respect to survival, recurrence and differential toxicity. In a factorial (2 x 2) trial design, QUASAR compared high-dose (175 mg) versus low-dose (25 mg) L-FA and levamisole versus placebo. The dose of 5-FU was fixed at 370 mg/m2 and although the recommended schedule was i.v. bolus delivery, daily for 5 days repeated four-weekly for 6 months, a significant proportion of randomising clinicians were constrained to deliver once-weekly 5-FU-L-FA for 30 weeks. Four thousand nine hundred twenty-seven patients were entered into QUASAR between May 1994 and October 1997, eighteen hundred twenty-nine of whom have recurred and sixteen hundred eighty-nine died. Similar numbers 2370 vs. 2559 were treated with the once-weekly and four-weekly schedules and the demographic features of the 2 groups were well balanced: stage C, 73.3% once-weekly vs. 71.0% four-weekly; colon, 68.0% vs. 68.3%; high-dose FA, 50.1% vs. 49.9%; levamisole, 49.3% vs. 49.3%; females, 40.2% vs. 41.7%; median age (years) 62 vs. 61. The risk of recurrence and survival were similar regardless of schedule: three-year survival was 70.6% once-weekly vs. 71.0% four-weekly; three-year recurrence risk was 35.6% once-weekly vs. 35.5% four-weekly; But, the once-weekly regimen was much less toxic: number of patients for whom toxicity was reported (once-weekly: four-weekly), stomatitis, 37 vs. 337; diarrhoea, 260 vs. 440; neutropenia, 20 vs. 153. The once-weekly regimen is much less toxic than and, apparently, about as effective as the four-weekly schedule. This suggests that the toxicity of 5-FU-L-FA adjuvant chemotherapy could be reduced substantially by weekly scheduling without

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2016-10-01

subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO...within the proposed time frame. 15. SUBJECT TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY...propose a randomized controlled trial to test that promise. There is compelling epidemiologic, in-vitro, and in-vivo, evidence of aspirin’s potential

Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study.

PubMed

Liang, Yi-Hsin; Shao, Yu-Yun; Chen, Ho-Min; Cheng, Ann-Lii; Lai, Mei-Shu; Yeh, Kun-Huei

2017-12-01

Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery. A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded. We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p<0.001). Irinotecan and oxaliplatin exhibited similar efficacy in patients who underwent curative surgery for resectable SCCLM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect.

PubMed

Bocci, Guido; Kerbel, Robert S

2016-11-01

Metronomic chemotherapy describes the close, regular administration of chemotherapy drugs at less-toxic doses over prolonged periods of time. In 2015, the results of randomized phase III clinical trials demonstrated encouraging, albeit limited, efficacy benefits of metronomic chemotherapy regimens administered as adjuvant maintenance therapy for the treatment of breast cancer, or as maintenance therapy in combination with an antiangiogenic agent for metastatic colorectal cancer. Owing to the investigational nature of this approach, metronomic chemotherapy regimens are highly empirical in terms of the optimal dose and schedule for the drugs administered; therefore, greater knowledge of the pharmacokinetics of metronomic chemotherapy is critical to the future success of this treatment strategy. Unfortunately, such preclinical and clinical pharmacokinetic studies are rare. Herein, we present situations in which active drug concentrations have been achieved with metronomic schedules, and discuss their associated pharmacokinetic parameters. We summarize examples from the limited number of clinical studies in order to illustrate the importance of assessing such pharmacokinetic parameters, and discuss the influence this information can have on improving efficacy and reducing toxicity.

Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

PubMed

Ruhstaller, T; Thuss-Patience, P; Hayoz, S; Schacher, S; Knorrenschild, J R; Schnider, A; Plasswilm, L; Budach, W; Eisterer, W; Hawle, H; Mariette, C; Hess, V; Mingrone, W; Montemurro, M; Girschikofsky, M; Schmidt, S C; Bitzer, M; Bedenne, L; Brauchli, P; Stahl, M

2018-04-04

This open-label, phase lll trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients were randomly assigned (1:1) to 2 cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary endpoint was progression-free survival (PFS). In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years (95% CI, 2.0 to not reached) with cetuximab and 2.0 years (95% CI, 1.5 to 2.8) with control (HR, 0.79; 95% CI, 0.58 to 1.07; P = .13). Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2 to 4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52 to 1.01; P = .055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31 to 0.90; P = .017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64 to 1.59, P = .97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. NCT01107639.

Observation versus adjuvant radiation or chemotherapy in the management of stage I seminoma: clinical outcomes and prognostic factors for relapse in a large US cohort.

PubMed

Soper, Margaret S; Hastings, Joseph R; Cosmatos, Harry A; Slezak, Jeffrey M; Wang, Ricardo; Lodin, Kenneth

2014-08-01

The management of stage I seminoma has evolved over the past 20 years. Contemporary management options after orchiectomy include adjuvant radiation, adjuvant chemotherapy, and observation. This analysis defines the experience at Kaiser Permanente Southern California from 1990 to 2010. We examined outcomes for stage I seminoma patients and reviewed prognostic factors for recurrence in those managed with observation. This is a retrospective study of 502 stage I seminoma patients who underwent orchiectomy from 1990 to 2010. Outcomes examined were relapse-free survival (RFS), overall survival (OS), and cause-specific survival (CSS). Risk factors for recurrence evaluated were age, preoperative hCG elevation, preoperative LDH elevation, tumor size, lymphovascular invasion, rete testis invasion, epididymis invasion, and invasion through the tunica albuginea. Among radiation patients, 5-year RFS was 97.2%, OS was 98.0%, and CSS was 99.3%. Among chemotherapy patients, 2-year RFS was 98.3% and OS and CSS were 100%. Among observation patients, 5-year RFS was 89.2%, OS was 98.8%, and CSS was 100%. There was no difference in OS or CSS among the groups. RFS was significantly lower for observation patients. Among observation patients, univariate analysis identified tumor size, lymphovascular invasion, and rete testis invasion as risk factors for relapse. No factors were significant on multivariate analysis. Our data show that adjuvant radiation and chemotherapy yield similar outcomes in the management of stage I seminoma. Observation results in a lower RFS, but patients who relapse can be salvaged; OS and CSS are not affected.

Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study

PubMed Central

Touillaud, M; Foucaut, A-M; Berthouze, S E; Reynes, E; Kempf-Lépine, A-S; Carretier, J; Pérol, D; Guillemaut, S; Chabaud, S; Bourne-Branchu, V; Perrier, L; Trédan, O; Fervers, B; Bachmann, P

2013-01-01

Introduction After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients’ satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. Methods and analysis The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. Ethics and dissemination The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy

German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer.

PubMed

von Minckwitz, Gunter; Möbus, Volker; Schneeweiss, Andreas; Huober, Jens; Thomssen, Christoph; Untch, Michael; Jackisch, Christian; Diel, Ingo J; Elling, Dirk; Conrad, Bettina; Kreienberg, Rolf; Müller, Volkmar; Lück, Hans-Joachim; Bauerfeind, Ingo; Clemens, Michael; Schmidt, Marcus; Noeding, Stefanie; Forstbauer, Helmut; Barinoff, Jana; Belau, Antje; Nekljudova, Valentina; Harbeck, Nadia; Loibl, Sibylle

2013-10-01

Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use. The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed. Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093). Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.

Emerging role of taxanes in adjuvant and neoadjuvant therapy for breast cancer: the potential and the questions.

PubMed

Goble, Sharon; Bear, Harry D

2003-08-01

Adjuvant chemotherapy has gained increasing prominence in the treatment of nonmetastatic breast cancer, producing gradual improvement in the survival of these patients. The taxanes offer great hope for adding to the progress in adjuvant treatment, but data have been conflicting. Early results of multi-center trials testing the sequential addition of paclitaxel to anthracycline-based adjuvant chemotherapy have perhaps been prematurely reported, but have already made a major impact on patterns of care for node-positive and even some node-negative patients. The early dramatic improvements in CALG 9344 are fading with time, however, and have not been confirmed by a second similar trial, NSABP B-28. Moreover, it cannot be stated with certainty whether the modest improvements observed by sequential addition of paclitaxel reflect the ability of this drug to kill anthracycline-resistant cancer cells or the increased total duration and amount of treatment. By contrast, the early results of the BCIRG 001 trial suggest that combining docetaxel with doxorubicin may significantly increase survival, but these early results should be viewed with caution and do not necessarily mean that docetaxel is superior to paclitaxel. The role of neoadjuvant chemotherapy for breast cancer has also expanded over the past 2 decades, from its initial use for inoperable locally advanced breast cancer (LABC) to its current use for patients with large operable tumors to make BCT feasible. The neoadjuvant approach also has an important role in clinical trials, where it will allow more rapid comparison of treatment regimens than can be accomplished in the adjuvant setting and provides an opportunity to analyze biologic markers as predictors of response. The value of this approach, however, will ultimately depend on a clear demonstration, not yet available, that a change in therapy that increases primary tumor response will also lead to improved long-term survival. The roles of docetaxel and

From total empiricism to a rational design of metronomic chemotherapy phase I dosing trials.

PubMed

Lam, Thomas; Hetherington, John W; Greenman, John; Maraveyas, Anthony

2006-02-01

'Metronomic chemotherapy' represents a novel anti-angiogenic strategy whereby low-dose chemotherapy is utilized in a continuous fashion in order to target tumor endothelium. There are many potential advantages of this strategy and clinical trials are already underway. However, although the scheduling of metronomic chemotherapy is relatively unequivocal, metronomic dosing principles are at present poorly defined. Arbitrarily, 10-33% of the maximum tolerated dose comprises 'the dose range'. We argue that this is too empirical and propose a set of phase I metronomic chemotherapy dosing strategies based on a principled approach which may help to reduce the problem of empiricism in dosing for metronomic chemotherapy trials.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

PubMed

Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

2018-05-01

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

Adjuvant therapy decisions based on magnetic resonance imaging of extramural venous invasion and other prognostic factors in colorectal cancer

PubMed Central

Swift, RI; Chau, I; Heald, RJ; Tekkis, PP; Brown, G

2014-01-01

Introduction There remains a lack of high quality randomised trial evidence for the use of adjuvant chemotherapy in stage II rectal cancer, particularly in the presence of high risk features such as extramural venous invasion (EMVI). The aim of this study was to explore this issue through a survey of colorectal surgeons and gastrointestinal oncologists. Methods An electronic survey was sent to a group of colorectal surgeons who were members of the Association of Coloproctology of Great Britain and Ireland. The survey was also sent to a group of gastrointestinal oncologists through the Pelican Cancer Foundation. Reminder emails were sent at 4 and 12 weeks. Results A total of 142 surgeons (54% response rate) and 99 oncologists (68% response rate) responded to the survey. The majority in both groups of clinicians thought EMVI was an important consideration in adjuvant treatment decision making and commented routinely on this in their multidisciplinary team meeting. Although both would consider treating patients on the basis of EMVI detected by magnetic resonance imaging, oncologists were more selective. Both surgeons and oncologists were prepared to offer patients with EMVI adjuvant chemotherapy but there was lack of consensus on the benefit. Conclusions This survey reinforces the evolution in thinking with regard to adjuvant therapy in stage II disease. Factors such as EMVI should be given due consideration and the prognostic information we offer patients must be more accurate. Historical data may not accurately reflect today’s practice and it may be time to consider an appropriately designed trial to address this contentious issue. PMID:25245736

Rethinking exercise identity: a qualitative study of physically inactive cancer patients' transforming process while undergoing chemotherapy.

PubMed

Adamsen, Lis; Andersen, Christina; Lillelund, Christian; Bloomquist, Kira; Møller, Tom

2017-08-23

To explore physically inactive breast and colon cancer patients' prediagnosis exercise history and attitudes to physical activity (PA) and experiences in initiating PA while undergoing adjuvant chemotherapy. An explorative qualitative study guided the interpretive analysis of semistructured, open-ended interviews conducted at initiation of chemotherapy and after 12 weeks. The study was embedded in a pilot randomised controlled trial. Participants were recruited from the Oncological Department at a hospital in Copenhagen, Denmark. 33 patients with cancer, median age 49 years: 25 patients with breast cancer and 8 with colon cancer, 72% with a low cardiac respiratory fitness level and the majority with a high level of education. Patients received adjuvant chemotherapy, oncologist's PA recommendation and exercise, cancer nurse specialist's counselling prior to allocation to PA interventions or waitlist control group. Prediagnosis exercise had been excluded from patients' daily lives due to perceptions of exercise as boring, lack of discipline and stressful work conditions for both genders. Recommendations from oncologists and nurses inspired the patients to reconsider their attitudes and behaviour by accepting recruitment and participation in PA interventions during chemotherapy. Despite extensive side effects, most patients adhered to their PA commitment due to their perception of the bodily, emotional and social benefits and support of healthcare professionals, peers and family. The patients' attitude towards exercise transformed from having no priority in patients' daily lives prediagnosis to being highly prioritised. This study identified four important phases in the exercise transformation process during the patients' treatment trajectory of relevance to clinicians in identifying, motivating and supporting physically inactive patients with cancer at long-term risk. Clinicians should address young, highly educated patients with cancer at onset of adjuvant

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Stenehjem, David D; Bellows, Brandon K; Yager, Kraig M; Jones, Joshua; Kaldate, Rajesh; Siebert, Uwe; Brixner, Diana I

2016-02-01

A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and

European cost-effectiveness study of uPA/PAI-1 biomarkers to guide adjuvant chemotherapy decisions in breast cancer.

PubMed

Marguet, Sophie; Mazouni, Chafika; Ramaekers, Bram L T; Dunant, Ariane; Kates, Ronald; Jacobs, Volker R; Joore, Manuela A; Harbeck, Nadia; Bonastre, Julia

2016-08-01

This study investigated the cost effectiveness of guideline-recommended (American Society of Clinical Oncology, European Society of Medical Oncology) urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) biomarkers to guide adjuvant chemotherapy decisions for hormone receptor-positive, node-negative early breast cancer patients at intermediate risk of relapse, in France, Germany, and The Netherlands. uPA/PAI-1 testing was compared to chemotherapy for all patients and to no chemotherapy in two age-related subgroups (35-49 and 50-75 years). A partitioned survival analysis was performed using patient-level data for survival outcomes and secondary sources. Mean quality-adjusted life years (QALYs) and costs were estimated over a lifetime horizon to calculate the incremental net monetary benefit (INMB) at a willingness-to-pay of €50,000/QALY. Uncertainty was explored through bootstrap and probabilistic sensitivity analysis using 5000 replicates. In the 35-49 year age group, INMBs were negative when uPA/PAI-1 testing was compared to chemotherapy for all patients but positive when it was compared to no chemotherapy for the three countries. In the 50-75 year age group, INMBs of uPA/PAI-1 testing compared to both reference strategies were positive in the three countries, with cost-effectiveness probabilities for the uPA/PAI-1 strategy of 65%, 70%, and 59% for France, Germany, and the Netherlands, respectively, compared with chemotherapy for all patients, and 64%, 58%, and 65%, respectively, compared with no chemotherapy. uPA/PAI-1 testing could allow the selection of patients older than 50 years requiring chemotherapy in this population, but the cost effectiveness of this strategy is uncertain. Chemotherapy for all patients is the most cost-effective strategy for patients younger than 50 years. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial.

PubMed

Nuzzo, Francesco; Morabito, Alessandro; Gravina, Adriano; Di Rella, Francesca; Landi, Gabriella; Pacilio, Carmen; Labonia, Vincenzo; Rossi, Emanuela; De Maio, Ermelinda; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; Thomas, Renato; Rinaldo, Massimo; Botti, Gerardo; Di Bonito, Maurizio; Di Maio, Massimo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2011-02-16

To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. ClinicalTrials.gov NCT00540800.

Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial.

PubMed

Kleckner, Ian R; Kamen, Charles; Gewandter, Jennifer S; Mohile, Nimish A; Heckler, Charles E; Culakova, Eva; Fung, Chunkit; Janelsins, Michelle C; Asare, Matthew; Lin, Po-Ju; Reddy, Pavan S; Giguere, Jeffrey; Berenberg, Jeffrey; Kesler, Shelli R; Mustian, Karen M

2018-04-01

Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms. Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness. Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076). Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients. Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Critical decision-making in radiotherapy for early stage breast cancer in a neo-adjuvant treatment era.

PubMed

De Felice, Francesca; Osti, Mattia Falchetto; De Sanctis, Vitaliana; Musio, Daniela; Tombolini, Vincenzo

2017-05-01

In breast cancer management, the role of adjuvant radiation therapy (RT) has been the subject of intense controversy over the past several years, due to the improvement in neoadjuvant chemotherapy (NACT) prescription. One of the most controversial questions regarding indication for adjuvant RT is whether or not RT is essential in patients with early stage disease at diagnosis. The value of adjuvant RT remains highly debatable in those patients with clinically negative nodes at the completion of NACT. Areas covered: This review is focused on this gray area and is intended to assist with clinical decision-making. We provide a comprehensive review using PubMed and meeting proceedings of San Antonio Breast Cancer Symposium, European Society for Radiotherapy & Oncology, European Society of Medical Oncology and American Society of Clinical Oncology. Expert commentary: The identification of potential prognostic factors may lead to novel adjuvant RT indications. Phase III clinical trials are underway and their results will help guide treatment decisions.

Filling in the gaps: reporting of concurrent supportive care therapies in breast cancer chemotherapy trials.

PubMed

Freedman, Orit; Amir, Eitan; Zimmermann, Camilla; Clemons, Mark

2011-03-01

Supportive care interventions can have a substantial impact on side effects of chemotherapy. Consequently, accurate reporting of such interventions is essential when interpreting clinical trial results. This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III, breast cancer chemotherapy trials. A systematic review of phase III trials of breast cancer trials incorporating chemotherapy published in the last 5 years was undertaken. Trials were identified through MEDLINE, EMBASE, BIOSIS, and the Cochrane Library. Supportive treatments evaluated were use of antiemetics, colony-stimulating growth factors, and antibiotics. Reporting quality was rated as "good", "fair", "poor", or "absent" using predetermined criteria. Sixty-two trials met inclusion criteria. In 41 studies (66%), details regarding prophylactic antiemetic treatment were not provided. Growth factor use was not reported in 20 trials (32%). Instructions for the use of prophylactic antibiotics were absent in 45 trials (72%). There are significant deficiencies in reporting of use of prophylactic supportive care agents in breast cancer trials. Omission of supportive care instructions may impact substantially on patient management and health care system expenditure. Recommendations for the type, dose, and frequency of supportive care drugs should be provided and reported on in trials.

Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial.

PubMed

Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

2015-07-10

In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22--ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and

Moxibustion for the treatment of chemotherapy-induced leukopenia: a systematic review of randomized clinical trials.

PubMed

Choi, Tae-Young; Lee, Myeong Soo; Ernst, Edzard

2015-06-01

The purpose of this study is to assess the efficacy of moxibustion as a treatment of chemotherapy-induced leukopenia. Twelve databases were searched from their inception through June 2014, without a language restriction. Randomized clinical trials (RCTs) were included if moxibustion was used as the sole treatment or as a part of a combination therapy with conventional drugs for leukopenia induced by chemotherapy. Cochrane criteria were used to assess the risk of bias. Six RCTs with a total of 681 patients met our inclusion criteria. All of the included RCTs were associated with a high risk of bias. The trials included patients with various types of cancer receiving ongoing chemotherapy or after chemotherapy. The results of two RCTs suggested the effectiveness of moxibustion combined with chemotherapy vs. chemotherapy alone. In four RCTs, moxibustion was more effective than conventional drug therapy. Six RCTs showed that moxibustion was more effective than various types of control interventions in increasing white blood cell counts. There is low level of evidence based on these six trials that demonstrates the superiority of moxibustion over drug therapies in the treatment of chemotherapy-induced leukopenia. However, the number of trials, the total sample size, and the methodological quality are too low to draw firm conclusions. Future RCTs appear to be warranted.

Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial

PubMed Central

Kesari, Santosh; Ram, Zvi

2017-01-01

Background: This post hoc analysis of the EF-14 trial (NCT00916409) of tumor-treating fields (TTFields) plus temozolomide versus temozolomide alone in newly diagnosed glioblastoma compared the efficacy of TTFields plus chemotherapy (physician’s choice) versus chemotherapy alone after first recurrence. Methods: Patients on TTFields plus temozolomide continued TTFields plus second-line chemotherapy after first recurrence. Some patients on temozolomide alone crossed over after approval of TTFields for recurrent GBM. The primary efficacy outcome was overall survival (OS). Results: After disease progression, 131 patients received TTFields plus chemotherapy and 73 chemotherapy alone. Thirteen patients in the original temozolomide-alone group crossed over to receive TTFields plus chemotherapy after disease progression, resulting in 144 patients receiving TTFields plus chemotherapy and 60 chemotherapy alone. Median follow-up was 12.6 months. Bevacizumab, alone or with cytotoxic chemotherapy, was the most frequent treatment. Median OS in the TTFields plus chemotherapy group was significantly longer versus chemotherapy alone (11.8 vs 9.2 months; HR: 0.70; 95% CI, 0.48–1.00; p=0.049). TTFields showed a low toxicity safety profile, as previously reported, with no grade 3/4 device-related adverse events. Conclusion: TTFields plus chemotherapy after first disease recurrence on TTFields plus temozolomide or temozolomide alone prolonged OS in patients in the EF-14 trial. PMID:28399638

Adjuvant Therapy in Early-Stage Endometrial Cancer: A Systematic Review of the Evidence, Guidelines, and Clinical Practice in the U.S.

PubMed Central

Latif, Nawar A.; Haggerty, Ashley; Jean, Stephanie; Lin, Lilie

2014-01-01

Endometrial cancer is the most common gynecologic malignancy in the U.S., with an increasing incidence likely secondary to the obesity epidemic. Surgery is usually the primary treatment for early stage endometrial cancer, followed by adjuvant therapy in selected cases. This includes radiation therapy [RT] with or without chemotherapy, based on stratification of patients into categories dependent on their future recurrence risk. Several prospective trials (PORTEC-1, GOG#99, and PORTEC-2) have shown that the use of adjuvant RT in the intermediate risk (IR) and the high-intermediate risk (HIR) groups decreases locoregional recurrence (LRR) but has no effect on overall survival. The ad hoc analyses from these studies have shown that an even larger LRR risk reduction was seen within the HIR group compared with the IR group. Vaginal brachytherapy is as good as external beam radiotherapy in controlling vaginal relapse where the majority of recurrence occur, and with less toxicity. In the high-risk group, multimodality therapy (chemotherapy and RT) may play a significant role. Although adjuvant RT has been evaluated in many cost-effectiveness studies, high-quality data in this area are still lacking. The uptake of the above prospective trial results in the U.S. has not been promising. Factors that are driving current practices and defining quality-of-care measures for patients with early-stage disease are what future studies need to address. PMID:24821823

Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials.

PubMed

Kroep, J R; Charehbili, A; Coleman, R E; Aft, R L; Hasegawa, Y; Winter, M C; Weilbaecher, K; Akazawa, K; Hinsley, S; Putter, H; Liefers, G J; Nortier, J W R; Kohno, N

2016-02-01

The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Editorial - Avoiding unethical Helicobacter pylori clinical trials: Susceptibility-based studies and probiotics as adjuvants

PubMed Central

Graham, David Y.

2016-01-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g. in a population with known clarithromycin resistance) is unethical. Since susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance greater than 0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies and of adjuvants and probiotics. However, the Journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors we provide examples and suggestion regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. PMID:26123529

OS02.1 Multicenter pilot study of radio-chemotherapy as first-line treatment for adults with medulloblastoma - the NOA-07 trial

PubMed Central

Beier, D.; Proescholdt, M.; Reinert, C.; Hattingen, E.; Seidel, C.; Dirven, L.; Lürding, R.; Pfister, S.; Pietsch, T.; Hau, P.

2017-01-01

Abstract Background: Medulloblastoma in adult patients has a low incidence, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. In contrast to children, no prospective data on the feasibility of radio-chemotherapy in adults exists. The German Neuro-Oncology Working Group (NOA) performed a prospective multicenter single-arm Phase II trial to evaluate the feasibility and toxicity of radio-chemotherapy in this population. Methods: The NOA-07 trial combined cranio-spinal irradiation with vincristine, followed by a maximum of eight cycles of cisplatin, lomustine and vincristine. Adverse events, imaging and progression patterns, combined histological and genetic markers, health-related quality of life (HRQoL) and cognition were evaluated prospectively. The primary endpoints were the rate of toxicity-related treatment terminations after four cycles of chemotherapy, and the toxicity profile. Findings: Thirty patients were evaluable. Fifty percent of patients showed classic, and 50% desmoplastic-nodular histology. Sixty-eight percent of patients were genetically classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13.6% in wingless (WNT), and 17.7% in Non-WNT/Non-SHH (Group 4). Four cycles of chemotherapy were feasible in the majority of patients (n=21; 70.0%). Leukopenia was the major toxicity, with 79 events of CTC grade 3 and 4 in 17 patients. Polyneuropathy and ototoxicity were the only grade 3 or 4 non-haematological toxicities during the active treatment phase and occurred 12 times in eight patients and one time in one patient, respectively. Events were also calculated per cycle and showed an increase of toxicity over treatment time. Feasibility appeared to be age-dependent, leading to application of four cycles of chemotherapy in 72.7% of patients below age 45 and 62.5% of patients 45 or above. Testing for all eight adjuvant cycles revealed that 45.5% of all patients younger than 45 years completed

Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in Invasive Breast Cancer.

PubMed

Jang, Nuri; Kwon, Hee Jung; Park, Min Hui; Kang, Su Hwan; Bae, Young Kyung

2018-04-01

This study investigated the prognostic value of tumor-infiltrating lymphocyte (TIL) density as determined by molecular subtype and receipt of adjuvant chemotherapy in invasive breast cancer (IBC). Stromal TIL densities were evaluated in 1489 IBC samples using recommendations proposed by the International TILs Working Group. Cases were allocated to high- and low-TIL density groups using a cutoff of 10%. Of the 1489 IBC patients, 427 (28.7%) were assigned to the high-TIL group and 1062 (71.3%) to the low-TIL group. High TIL density was found to be significantly associated with large tumor size (p = 0.001), high histologic grade (p < 0.001), and high Ki-67 labeling index (p < 0.001). Triple-negative and human epidermal growth factor receptor 2 (HER2)-positive subtypes had significantly higher TIL densities than luminal A or B (HER2-negative) subtypes (p < 0.001). High TIL density was significantly associated with prolonged disease-free survival (DFS) by univariate (p < 0.001) and multivariate (p < 0.001) analyses. In the low-TIL-density group, the patients who did not receive adjuvant chemotherapy showed better DFS (p < 0.001), but no such survival difference was observed in the high-TIL group (p = 0.222). For the patients who received adjuvant anthracycline, high-TIL density was found to be an independent prognostic factor of favorable DFS in the luminal B (HER2-negative; p = 0.003), HER2-positive (p = 0.019), and triple-negative (p = 0.017) subtypes. Measurements of TIL density in routine clinical practice could give useful prognostic information for the triple-negative, HER2-positive, and luminal B (HER2-negative) IBC subtypes, especially for patients administered adjuvant anthracycline.

Cost effectiveness of molecular profiling for adjuvant decision making in patients with node-negative breast cancer.

PubMed

Bonastre, Julia; Marguet, Sophie; Lueza, Beranger; Michiels, Stefan; Delaloge, Suzette; Saghatchian, Mahasti

2014-11-01

To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) -positive patients. We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, -€642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy. Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost effective in patients with NNBC. © 2014 by American Society of Clinical Oncology.

Risk factors for financial hardship in patients receiving adjuvant chemotherapy for colon cancer: a population-based exploratory analysis.

PubMed

Shankaran, Veena; Jolly, Sanjay; Blough, David; Ramsey, Scott D

2012-05-10

Characteristics that predispose patients to financial hardship during cancer treatment are poorly understood. We therefore conducted a population-based exploratory analysis of potential factors associated with financial hardship and treatment nonadherence during and following adjuvant chemotherapy for colon cancer. Patients diagnosed with stage III colon cancer between 2008 and 2010 were identified from a population-based cancer registry representing 13 counties in Washington state. Patients were asked to complete a comprehensive survey on treatment-related costs. Patients were considered to have experienced financial hardship if they accrued debt, sold or refinanced their home, borrowed money from friends or family, or experienced a 20% or greater decline in their annual income as a result of treatment-related expenses. Logistic regression analysis was used to investigate factors associated with financial hardship and treatment nonadherence. A total of 284 responses were obtained from 555 eligible patients (response rate, 51.2%). Nearly all patients in the final sample were insured during treatment. In this sample, 38% of patients reported one or more financial hardships as a result of treatment. The factors most closely associated with treatment-related financial hardship were younger age and lower annual household income. Younger age, lower income, and unemployment or disability (which occurred in most instances following diagnosis) were most closely associated with treatment nonadherence. A significant proportion of patients undergoing adjuvant chemotherapy for stage III colon cancer may experience financial hardship, despite having health insurance coverage. Interventions to help at-risk patients early on during therapy may prevent long-term financial adverse effects.

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): a systematic review.

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul P; Linnane, Anthony W; Vitetta, Luis

2013-12-01

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

PubMed

Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2006-08-10

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Current palliative chemotherapy trials in the elderly neglect patient-centred outcome measures.

PubMed

van Bekkum, Marlies L; van Munster, Barbara C; Thunnissen, Peter L M; Smorenburg, Carolien H; Hamaker, Marije E

2015-01-01

The elderly comprise the majority of patients newly diagnosed with cancer. Despite this, little evidence-based data are available on the care of the growing number of older patients with cancer. The objective of the current study was to evaluate the characteristics and outcome measures of current clinical trials on palliative chemotherapy in elderly patients. Fourteen international clinical trials registries were searched using the terms "cancer" and "elderly" to identify clinical palliative chemotherapy trials designed specifically for patients aged 70+ years. From the trial protocol, data were extracted on trial characteristics and outcome measures. Of 127 trials, 81% formulated one or more stringent criteria with respect to organ function; 32% excluded patients with WHO performance status (PS) 2 and 83% with PS3. Functional outcomes, health care utilisation, cognitive function after treatment, and quality of life were reported in 6%, 3%, 6%, and 31% of trials, respectively. In only 16% of trials on palliative cancer treatment, a geriatric assessment was performed at baseline. Although recent years have seen a growing evidence base regarding fit older patients, our study suggests a lack of representative cohorts of older patients and patient-centred outcome measures in current palliative treatment trials for the elderly. Research addressing alternative outcome measures, including quality of life and impact of therapy on general functioning, cognition, and preservation of independence, and incorporation of a geriatric assessment are needed to provide elderly patients with cancer and their treating physicians with realistic information about palliative chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

PubMed

Kim, Se-Hyuk; Yoo, Heon; Chang, Jong Hee; Kim, Chae-Yong; Chung, Dong Sup; Kim, Se Hoon; Park, Sung-Hae; Lee, Youn Soo; Yang, Seung Ho

2018-06-11

While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O 6 -methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m 2 ) on day 1 and procarbazine (60 mg/m 2 ) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Effect of Red Ginseng on Genotoxicity and Health-Related Quality of Life after Adjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer: A Randomized, Double Blind, Placebo-Controlled Trial.

PubMed

Kim, Hee Seung; Kim, Mi-Kyung; Lee, Maria; Kwon, Byung-Su; Suh, Dong Hoon; Song, Yong Sang

2017-07-19

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo ( n = 15) and red ginseng groups ( n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer.

PubMed

Maeda, Tetsuyo; Nakanishi, Yoko; Hirotani, Yukari; Fuchinoue, Fumi; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao; Nemoto, Norimichi

2016-03-01

Triple negative breast cancer (TNBC) is immunohistochemically characterised by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2). TNBC is known for its poor prognosis and high recurrence probability. There is no effective targeted treatment for TNBC, but only adjuvant chemotherapies. There are two TNBC subtypes, basal-like and non-basal-like, which are defined based on positive cytokeratin (CK) 5/6 and/or epidermal growth factor receptor (EGFR) expression. In particular, CK5/6 expression is reported to correlate with TNBC recurrence. TNBC lacks ER-α expression, but some TNBCs are known to express the androgen receptor (AR). Moreover, although p53 accumulation is detected in various malignant tumors, its influence on adjuvant chemotherapy for patients with TNBC remains unclear. The aim of this study was to assess the combined immunohistochemical expression of CK 5/6, AR, and p53 as a potential prognostic marker of adjuvant chemotherapy for patients with TNBC. The expression of CK5/6, AR, and p53 in formalin-fixed and paraffin-embedded (FFPE) surgical sections from 52 patients with TNBC was analysed by immunohistochemistry (IHC) and the co-expression patterns in individual cells were investigated by immunofluorescent (IF) staining. Low AR expression was correlated with high clinical stage (P < 0.05) and low nuclear grade (P < 0.05). The expression of CK5/6 and p53 did not correlate with clinicopathological features. Patients who needed adjuvant chemotherapy presented the worst prognosis. In particular, when the IHC expression pattern was CK5/6 (-), AR (-), and p53 (+), the disease free survival (DFS) and overall survival (OS) were the worst. On the other hand, patients with AR (+) and p53 (-) TNBC presented a good prognosis. The analysis of the co-expression status of these three markers showed that no cells presented both AR and CK5/6 expression. Furthermore, TP53 m

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.

Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakst, Richard L.; Lee, Nancy; Pfister, David G.

2011-05-01

Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are asmore » follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.« less

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients

PubMed Central

Deserti, Marzia; Vasuri, Francesco; Farioli, Andrea; Degiovanni, Alessio; Palloni, Andrea; Frega, Giorgio; Barbera, Maria A.; de Lorenzo, Stefania; Garajova, Ingrid; Di Marco, Mariacristina; Pinna, Antonio D.; Cescon, Matteo; Cucchetti, Alessandro; Ercolani, Giorgio; D’Errico-Grigioni, Antonietta; Pantaleo, Maria A.; Biasco, Guido; Tavolari, Simona

2016-01-01

Background. The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Methods. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Results. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24–0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34–2.68; three to four cycles: HR 0.99, 95% CI 0.34–2.90; five to six cycles: HR 0.27, 95% CI 0.10–0.77). Conclusion. hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. Implications for Practice: Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients.

PubMed

Brandi, Giovanni; Deserti, Marzia; Vasuri, Francesco; Farioli, Andrea; Degiovanni, Alessio; Palloni, Andrea; Frega, Giorgio; Barbera, Maria A; de Lorenzo, Stefania; Garajova, Ingrid; Di Marco, Mariacristina; Pinna, Antonio D; Cescon, Matteo; Cucchetti, Alessandro; Ercolani, Giorgio; D'Errico-Grigioni, Antonietta; Pantaleo, Maria A; Biasco, Guido; Tavolari, Simona

2016-05-01

The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24-0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34-2.68; three to four cycles: HR 0.99, 95% CI 0.34-2.90; five to six cycles: HR 0.27, 95% CI 0.10-0.77). hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are available on predictive biomarkers of response. In this study, patients

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.

PubMed

von Minckwitz, Gunter; Procter, Marion; de Azambuja, Evandro; Zardavas, Dimitrios; Benyunes, Mark; Viale, Giuseppe; Suter, Thomas; Arahmani, Amal; Rouchet, Nathalie; Clark, Emma; Knott, Adam; Lang, Istvan; Levy, Christelle; Yardley, Denise A; Bines, Jose; Gelber, Richard D; Piccart, Martine; Baselga, Jose

2017-07-13

Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

PubMed

Piringer, Gudrun; Fridrik, Michael; Fridrik, Alfred; Leiherer, Andreas; Zabernigg, August; Greil, Richard; Eisterer, Wolfgang; Tschmelitsch, Jörg; Lang, Alois; Frantal, Sophie; Burgstaller, Sonja; Gnant, Michael; Thaler, Josef

2018-04-01

Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta-analysis of randomized trials.

PubMed

Restellini, Sophie; Kherad, Omar; Menard, Charles; Martel, Myriam; Barkun, Alan N

2018-02-01

BACKGROUND AND STUDY AIMS : Recommendations on adjuvant use with bowel preparations remain disparate. We performed a meta-analysis determining the clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens.  Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials from January 1980 to April 2016 that assessed preparations with or without adjuvants, given in split and non-split dosing, and PEG high- (> 3 L) or low-dose (≤ 2 L) regimens. Bowel cleansing efficacy was the primary outcome. Secondary outcomes included patient willingness to repeat the procedure, and polyp and adenoma detection rates.  Of 3093 citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an adjuvant compared with no adjuvant, irrespective of the type of preparation and mode of administration, yielded improvements in bowel cleanliness (odds ratio [OR] 1.23 [1.01 - 1.51]) without greater willingness to repeat (OR 1.40 [0.91 - 2.15]). Adjuvants combined with high-dose PEG significantly improved colon cleansing (OR 1.96 [1.32 - 2.94]). The odds for achieving adequate preparation with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR 0.95 [0.73 - 1.22]), but yielded improved tolerance (OR 3.22 [1.85 - 5.55]). However, split high-dose PEG yielded superior cleanliness to low-dose PEG with adjuvants (OR 2.53 [1.25 - 5.13]). No differences were noted for OSS and PICO comparisons, or for any products regarding polyp or adenoma detection rates.  Critical heterogeneity precludes firm conclusion on the impact of adjuvants with existing bowel preparations. Additional research is required to better characterize the methods of administration and resulting roles of adjuvants in an era of split-dosing. © Georg Thieme Verlag KG Stuttgart · New York.

Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial.

PubMed

Ignatiadis, Michail; Rack, Brigitte; Rothé, Francoise; Riethdorf, Sabine; Decraene, Charles; Bonnefoi, Hervé; Dittrich, Christian; Messina, Carlo; Beauvois, Melanie; Trapp, Elisabeth; Goulioti, Theodora; Tryfonidis, Konstantinos; Pantel, Klaus; Repollet, Madeline; Janni, Wolfgang; Piccart, Martine; Sotiriou, Christos; Litiere, Saskia; Pierga, Jean-Yves

2016-08-01

There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer. The ongoing Treat CTC trial is the first international, liquid biopsy-based trial evaluating the concept of targeting chemoresistant minimal residual disease: detection of CTCs following adjuvant chemotherapy (adjuvant cohort) or neoadjuvant chemotherapy in patients who did not achieve pathological complete response (neoadjuvant cohort). This article presents the rational and design of this trial and the results of the pilot phase after 350 patients have been screened and provides insights that might provide information for future trials using the liquid biopsy approach as a tool towards precision medicine (NCT01548677). Copyright © 2016 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenfeld, Jonathan D., E-mail: jdschoenfeld@partners.org; Sher, David J.; Norris, Charles M.

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 carcinomamore » 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

Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants.

PubMed

Graham, David Y

2015-10-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. © 2015 John Wiley & Sons Ltd.

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.

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients - Open-labeled randomized clinical trial.

PubMed

Chen, Chung-Hsin; Pu, Yeong-Shiau

2018-06-01

To investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). This open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. The adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. Adjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort. Copyright © 2018. Published by Elsevier Inc.

Compliance, satisfaction, and quality of life of patients with colorectal cancer receiving home chemotherapy or outpatient treatment: a randomised controlled trial.

PubMed

Borras, J M; Sanchez-Hernandez, A; Navarro, M; Martinez, M; Mendez, E; Ponton, J L; Espinas, J A; Germa, J R

2001-04-07

To compare chemotherapy given at home with outpatient treatment in terms of colorectal cancer patients' safety, compliance, use of health services, quality of life, and satisfaction with treatment. Randomised controlled trial. Large teaching hospital. 87 patients receiving adjuvant or palliative chemotherapy for colorectal cancer. Treatment with fluorouracil (with or without folinic acid or levamisole) at outpatient clinic or at home. Treatment toxicity; patients' compliance with treatment, quality of life, satisfaction with care, and use of health resources. 42 patients were treated at outpatient clinic and 45 at home. The two groups were balanced in terms of age, sex, site of cancer, and disease stage. Treatment related toxicity was similar in the two groups (difference 7% (95% confidence interval -12% to 26%)), but there were more voluntary withdrawals from treatment in the outpatient group than in the home group (14% v 2%, difference 12% (1% to 24%)). There were no differences between groups in terms of quality of life scores during and after treatment. Levels of patient satisfaction were higher in the home treatment group, specifically with regard to information received and nursing care. There were no significant differences in use of health services. Home chemotherapy seemed an acceptable and safe alternative to hospital treatment for patients with colorectal cancer that may improve compliance and satisfaction with treatment.

Exercise for women receiving adjuvant therapy for breast cancer.

PubMed

Furmaniak, Anna C; Menig, Matthias; Markes, Martina H

2016-09-21

A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. Two review authors independently performed data extraction, assessed trials, and graded the

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

PubMed

Tang, Monica; Price, Timothy Jay; Shapiro, Jeremy; Gibbs, Peter; Haller, Daniel G; Arnold, Dirk; Peeters, Marc; Segelov, Eva; Roy, Amitesh; Tebbutt, Niall; Pavlakis, Nick; Karapetis, Chris; Burge, Matthew

2018-04-01

Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Elderly postmenopausal patients with breast cancer are at increased risk for distant recurrence: a tamoxifen exemestane adjuvant multinational study analysis.

PubMed

van de Water, Willemien; Seynaeve, Caroline; Bastiaannet, Esther; Markopoulos, Christos; Jones, Steve E; Rea, Daniel; Hasenburg, Annette; Putter, Hein; Hille, Elysée T M; Paridaens, Robert; de Craen, Anton J M; Westendorp, Rudi G J; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

2013-01-01

For postmenopausal patients with hormone-sensitive breast cancer, outcome is worse with increasing age at diagnosis. The aim of this study was to assess the incidence of breast cancer recurrence (locoregional and distant), and contralateral breast cancer by age at diagnosis. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. Primary endpoints were locoregional recurrence, distant recurrence, and contralateral breast cancer. Age at diagnosis was categorized as younger than 65 years, 65-74 years, and 75 years or older. Overall, 9,766 patients were included, of which 5,349 were younger than 65 years (reference group), 3,060 were 65-74 years, and 1,357 were 75 years or older. With increasing age, a decreased administration of radiotherapy after breast conserving surgery (94%, 92%, and 88%, respectively) and adjuvant chemotherapy (51%, 23%, and 5%, respectively) was observed. Risk of distant recurrence increased with age at diagnosis; multivariable hazard ratio for patients aged 65-74 years was 1.20 (95% confidence interval [CI]: 1.00-1.44), hazard ratio for patients aged 75 years or older was 1.39 (95% CI: 1.08-1.79). Risks of locoregional recurrence and contralateral breast cancer were not significantly different across age groups. Elderly patients with breast cancer were at increased risk for distant recurrence. Other studies have shown that the risk of distant recurrence is mainly affected by adjuvant systemic therapy. All TEAM patients received adjuvant endocrine treatment; however, chemotherapy was administered less often in elderly patients. These findings are suggestive for consideration of chemotherapy in relatively fit elderly breast cancer patients with hormone-sensitive disease.

Elderly Postmenopausal Patients With Breast Cancer Are at Increased Risk for Distant Recurrence: A Tamoxifen Exemestane Adjuvant Multinational Study Analysis

PubMed Central

van de Water, Willemien; Seynaeve, Caroline; Bastiaannet, Esther; Markopoulos, Christos; Jones, Steve E.; Rea, Daniel; Hasenburg, Annette; Putter, Hein; Hille, Elysée T.M.; Paridaens, Robert; de Craen, Anton J.M.; Westendorp, Rudi G.J.; Liefers, Gerrit-Jan

2013-01-01

Introduction. For postmenopausal patients with hormone-sensitive breast cancer, outcome is worse with increasing age at diagnosis. The aim of this study was to assess the incidence of breast cancer recurrence (locoregional and distant), and contralateral breast cancer by age at diagnosis. Methods. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. Primary endpoints were locoregional recurrence, distant recurrence, and contralateral breast cancer. Age at diagnosis was categorized as younger than 65 years, 65–74 years, and 75 years or older. Results. Overall, 9,766 patients were included, of which 5,349 were younger than 65 years (reference group), 3,060 were 65–74 years, and 1,357 were 75 years or older. With increasing age, a decreased administration of radiotherapy after breast conserving surgery (94%, 92%, and 88%, respectively) and adjuvant chemotherapy (51%, 23%, and 5%, respectively) was observed. Risk of distant recurrence increased with age at diagnosis; multivariable hazard ratio for patients aged 65–74 years was 1.20 (95% confidence interval [CI]: 1.00–1.44), hazard ratio for patients aged 75 years or older was 1.39 (95% CI: 1.08–1.79). Risks of locoregional recurrence and contralateral breast cancer were not significantly different across age groups. Conclusion. Elderly patients with breast cancer were at increased risk for distant recurrence. Other studies have shown that the risk of distant recurrence is mainly affected by adjuvant systemic therapy. All TEAM patients received adjuvant endocrine treatment; however, chemotherapy was administered less often in elderly patients. These findings are suggestive for consideration of chemotherapy in relatively fit elderly breast cancer patients with hormone-sensitive disease. PMID:23263290

Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial.

PubMed

Gronchi, Alessandro; Ferrari, Stefano; Quagliuolo, Vittorio; Broto, Javier Martin; Pousa, Antonio Lopez; Grignani, Giovanni; Basso, Umberto; Blay, Jean-Yves; Tendero, Oscar; Beveridge, Robert Diaz; Ferraresi, Virginia; Lugowska, Iwona; Merlo, Domenico Franco; Fontana, Valeria; Marchesi, Emanuela; Donati, Davide Maria; Palassini, Elena; Palmerini, Emanuela; De Sanctis, Rita; Morosi, Carlo; Stacchiotti, Silvia; Bagué, Silvia; Coindre, Jean Michelle; Dei Tos, Angelo Paolo; Picci, Piero; Bruzzi, Paolo; Casali, Paolo Giovanni

2017-06-01

Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland. Eligible patients were aged 18 years or older with localised, high-risk (high malignancy grade, 5 cm or longer in diameter, and deeply located according to the investing fascia), soft-tissue sarcoma of the extremities or trunk wall and belonging to one of five histological subtypes: high-grade myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma. Patients were randomly assigned (1:1) to receive three cycles of full-dose standard chemotherapy (epirubicin 60 mg/m 2 per day [short infusion, days 1 and 2] plus ifosfamide 3 g/m 2 per day [days 1, 2, and 3], repeated every 21 days) or histotype-tailored chemotherapy: for high-grade myxoid liposarcoma, trabectedin 1·3 mg/m 2 via 24-h continuous infusion, repeated every 21 days; for leiomyosarcoma, gemcitabine 1800 mg/m 2 on day 1 intravenously over 180 min plus dacarbazine 500 mg/m 2 on day 1 intravenously over 20 min, repeated every 14 days; for synovial sarcoma, high-dose ifosfamide 14 g/m 2 , given over 14 days via an external infusion pump, every 28 days; for malignant peripheral nerve sheath tumour, intravenous etoposide 150 mg/m 2 per day (days 1, 2, and 3) plus intravenous ifosfamide 3 g/m 2 per day (days 1, 2, and 3), repeated every 21 days; and for undifferentiated pleomorphic sarcoma, gemcitabine 900 mg/m 2 on days 1 and

Can Aidi injection restore cellular immunity and improve clinical efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy? A meta-analysis of 17 randomized controlled trials following the PRISMA guidelines.

PubMed

Xiao, Zheng; Wang, Chengqiong; Sun, Yongping; Li, Nana; Li, Jing; Chen, Ling; Yao, Xingsheng; Ding, Jie; Ma, Hu

2016-11-01

Aidi injection is an adjuvant chemotherapy drug commonly used in China. Can Aidi injection restore the cellular immunity and improve the clinical efficacy in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy? There is a lack of strong evidence to prove it. To further reveal it, we systematically evaluated all related studies. We collected all studies about the clinical efficacy and cellular immunity of Aidi injection plus platinum-based chemotherapy for NSCLC in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China biological medicine database (CBM) (established to June 2015), Cochrane Central Register of Controlled Trials (CCRCT) (June 2015), Chinese clinical trial registry, and US-clinical trials (June 2015). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the patient intervention control group outcomes principles and synthesized the data by meta-analysis. Seventeen (RCTs) with 1390 NSCLC patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR) and disease control rate (DCR) were as follows: 1.26 (1.12, 1.42) and 1.11(1.04, 1.17). The merged standardized mean difference (SMD) values and their 95% CI of meta-analysis for the percentage of CD3T cells, CD4T cells, CD8T cells, natural killer (NK) cells, and CD4/CD8 T cell ratio were as follows: 1.41, (0.89, 1.92), 1.59, (1.07, 2.11), 0.85, (0.38, 1.33), 1.64 (0.89, 2.39) and 0.91, (0.58, 1.24). Compared with platinum-based chemotherapy alone, all differences were statistically significant. These results might be overestimated or underestimated. Aidi injection plus platinum-based chemotherapy can improve the clinical efficacy of patients with NSCLC. Aidi

Association Between Geographic Access to Cancer Care, Insurance, and Receipt of Chemotherapy: Geographic Distribution of Oncologists and Travel Distance.

PubMed

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

2015-10-01

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 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. 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). 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. © 2015 by American Society of Clinical Oncology.

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

[Music as an adjuvant treatment for anxiety in pediatric oncologic patients].

PubMed