Colchicine in therapy. State of the art and new perspectives for an old drug.

PubMed

Famaey, J P

1988-01-01

Colchicine is the most specific treatment in acute gouty attacks. In several European countries, oral colchicine is still used for routine treatment of acute gout. Its selectivity is used as a diagnostic tool. It is also active in the treatment of acute crises of chondrocalcinosis and more occasionally of other arthritic crises (e.g. sarcoidosis). Colchicine appears to be the necessary adjuvant prophylactic drug when starting a hypouricemic treatment with uricosuric or uricolytic drugs for avoiding acute gouty crisis due to sudden mobilisation of the uric acid pool. Besides gout, colchicine is the drug of choice for treating familial mediterranean fever. It appears to be helpful in the treatment of Behçet's disease. It seems also useful for treating fibrosing conditions such as liver cirrhosis and scleroderma. As an adjuvant therapy, it helps treating dermatological disorders which are associated with leucocyte migration as an essential pathogenic factor (e.g. psoriasis, dermatitis herpetiformis, necrotising vasculitis ...). It has been advocated as an adjuvant therapy in malignant diseases as a support in radiotherapy and as an useful drug in various other diseases where it has been tried occasionally (e.g. Paget's disease of the bone, idiopathic thrombocytopenic purpura, disc syndrome). This very old drug remains a modern therapeutic agent.

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

PubMed

Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. Copyright © 2011 Elsevier Ltd. All rights reserved.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

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

McMillan, Matthew T.; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Ojerholm, Eric

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiationmore » therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.« less

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.

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria.

PubMed

Hiben, Mebrahtom Gebrelibanos; Sibhat, Gereziher Gebremedhin; Fanta, Biruk Sintayehu; Gebrezgi, Haile Desta; Tesema, Shewaye Belay

2016-01-01

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy.

Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

Cancer.gov

A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men.

PubMed

Venigalla, Sriram; Carmona, Ruben; Guttmann, David M; Jain, Varsha; Freedman, Gary M; Clark, Amy S; Shabason, Jacob E

2018-05-24

Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Receipt of adjuvant endocrine therapy. Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P < .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P < .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P < .001) or chemotherapy

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

Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

PubMed Central

Swanton, Charles; Szallasi, Zoltan; Brenton, James D; Downward, Julian

2008-01-01

The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and 5-fluorouracil, targeted agents such as trastuzumab and inhibitors of AKT and Poly(ADP-ribose) polymerase (PARP) as well as endocrine therapies such as tamoxifen. Given the limited power of microarray signatures to predict therapeutic response in associative studies of small clinical trial cohorts, the use of functional genomic data combined with expression or sequence analysis of genes and microRNAs implicated in drug response in human tumours may provide a more robust method to guide adjuvant treatment strategies in breast cancer that are transferable across different expression platforms and patient cohorts. PMID:18986507

Trends and variations in the use of adjuvant therapy for patients with head and neck cancer.

PubMed

Chen, Michelle M; Roman, Sanziana A; Yarbrough, Wendell G; Burtness, Barbara A; Sosa, Julie A; Judson, Benjamin L

2014-11-01

The National Comprehensive Cancer Network guidelines recommend that patients with surgically resected head and neck cancers that have adverse pathologic features should receive adjuvant therapy in the form of radiotherapy (RT) or chemoradiation (CRT). To the authors' knowledge, the current study is the first analysis of temporal trends and use patterns of adjuvant therapy for these patients. Patients with head and neck cancer and adverse pathologic features were identified in the National Cancer Data Base (1998-2011). Data were analyzed using chi-square, Student t, and log-rank tests; multivariate logistic regression; and Cox multivariate regression. A total of 73,088 patients were identified: 41.5% had received adjuvant RT, 33.5% had received adjuvant CRT, and 25.0% did not receive any adjuvant therapy. From 1998 to 2011, the increase in the use of adjuvant CRT was greatest for patients with oral cavity (6-fold) and laryngeal (5-fold) cancers. Multivariate analysis demonstrated that Medicare/Medicaid insurance (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.01-1.11), distance ≥34 miles from the cancer center (OR, 1.66; 95% CI, 1.59-1.74), and academic (OR, 1.26; 95% CI, 1.20-1.31) and high-volume (OR, 1.10; 95% CI, 1.05-1.15) centers were independently associated with patients not receiving adjuvant therapy. Receipt of adjuvant therapy was found to be independently associated with improved overall survival (hazard ratio, 0.84; 95% CI, 0.81-0.86). Approximately 25% of patients are not receiving National Comprehensive Cancer Network guideline-directed adjuvant therapy. Patient-level and hospital-level factors are associated with variations in the receipt of adjuvant therapy. Further evaluation of these differences in practice patterns is needed to standardize practice and potentially improve the quality of care. Cancer 2014;120:3353-3360. © 2014 American Cancer Society. © 2014 American Cancer Society.

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.

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.

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria

PubMed Central

Hiben, Mebrahtom Gebrelibanos; Sibhat, Gereziher Gebremedhin; Fanta, Biruk Sintayehu; Gebrezgi, Haile Desta; Tesema, Shewaye Belay

2015-01-01

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy. PMID:26870688

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

PubMed

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

PubMed Central

Liao, Guo-Shiou; Shyur, Lie-Fen

2013-01-01

Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy. PMID:23840256

Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats.

PubMed

Refaat, Rowaida; Salama, Mona; Abdel Meguid, Elham; El Sarha, Ashgan; Gowayed, Mennatallah

2013-01-05

There is increasing body of evidence documenting the involvement of angiotensin II in inflammatory diseases. Moreover the up-regulation of angiotensin II AT(1) receptors in the synovium of rheumatoid arthritis patients has been previously described. This study aimed at investigating the anti-inflammatory effect of losartan, the selective angiotensin II AT(1) receptor blocker, and comparing the efficacy of methotrexate alone and in combination with losartan in adjuvant arthritis in rats. Twelve days post adjuvant injection, Sprague-Dawley rats were treated with methotrexate (1mg/kg/week), losartan (20mg/kg/day) and their combination for 15 days. Severity of arthritis was assessed by hind paw swelling, arthrogram scores. Serum was analyzed for measurement of albumin, C-reactive protein (CRP), nitrite/nitrate concentrations, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), aspartate transaminase (AST) and alanine transaminase (ALT). Histopathological examination was done for hind paws and livers. Methotrexate and losartan monotherapies significantly reduced all parameters of inflammation and arthritis with better results in the methotrexate group except for the transaminases where losartan caused more significant reduction in their serum levels. The combined therapy showed better results than methotrexate and losartan alone. Hind paws showed better improvement of inflammatory cell infiltration and bone resorption in the combined therapy group. Disturbances in liver architecture and fibrosis caused by adjuvant arthritis were reverted to normal status in the combined therapy group in contrast to losartan and methotrexate monotherapies. In conclusion, methotrexate and losartan combined therapy provided more effective anti-inflammatory and hepatoprotective effects than either drug alone. Copyright © 2012 Elsevier B.V. All rights reserved.

Breast-cancer adjuvant therapy with zoledronic acid.

PubMed

Coleman, Robert E; Marshall, Helen; Cameron, David; Dodwell, David; Burkinshaw, Roger; Keane, Maccon; Gil, Miguel; Houston, Stephen J; Grieve, Robert J; Barrett-Lee, Peter J; Ritchie, Diana; Pugh, Julia; Gaunt, Claire; Rea, Una; Peterson, Jennifer; Davies, Claire; Hiley, Victoria; Gregory, Walter; Bell, Richard

2011-10-13

Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths--243 in the zoledronic acid group and 276 in the control group--were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.).

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

Enhancement of bone consolidation in mandibular distraction osteogenesis: a contemporary review of experimental studies involving adjuvant therapies.

PubMed

Hong, Paul; Boyd, Daniel; Beyea, Steven D; Bezuhly, Michael

2013-07-01

One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Effects of a brief psychosocial intervention in patients with cancer receiving adjuvant therapy.

PubMed

Oh, Pok Ja; Kim, Soo Hyun

2010-03-01

To test the effects of a brief psychosocial intervention using CD-ROM (BPIC) on psychosocial (fighting spirit, helplessness or hopelessness, anxiety, and depression) and behavioral (self-care behaviors) outcomes in patients with cancer receiving adjuvant therapy. Quasi-experimental. A comprehensive cancer center in Seoul, South Korea. 71 patients undergoing adjuvant therapy. The study participants were assigned to either BPIC or a control group. The experimental group underwent a two-week psychosocial intervention via CD-ROM, booklet, and telephone counseling. Fighting spirit, helplessness or hopelessness, anxiety, depression, and self-care behaviors. After BPIC, the experimental group showed significantly higher scores than the control group for fighting spirit (p = 0.005) and self-care behaviors (p < 0.001). However, the groups showed no significant differences in helplessness or hopelessness (p = 0.42), anxiety (p = 0.279), and depression (p = 0.068). BPIC use improved fighting spirit and self-care behaviors in study participants. The results partially support the effectiveness of BPIC for adaptation among patients with cancer receiving adjuvant therapy. A brief psychosocial intervention using multimedia can be used effectively in clinical oncology settings to accelerate adaptation among patients with cancer in the adjuvant phase.

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.

Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

PubMed

Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

2015-06-01

The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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 .

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

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

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.

2009-09-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. Onmore » univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.« less

Lymphadenectomy and Adjuvant Therapy Improve Survival with Uterine Carcinosarcoma: A Large Retrospective Cohort Study.

PubMed

Versluis, Marco A C; Pielsticker, Cindy; van der Aa, Maaike A; de Bruyn, Marco; Hollema, Harry; Nijman, Hans W

2018-05-23

Uterine carcinosarcoma is a rare, aggressive subtype of endometrial cancer. Treatment consists of hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy (LND). The survival benefit of LND in relation to adjuvant radio- and/or chemotherapy is unclear. We evaluated the impact of LND on survival in relation to adjuvant therapy in uterine carcinosarcoma. Retrospective data on 1,140 cases were combined from the Netherlands Cancer Registry (NCR) and the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). LND was defined as the removal of any nodes. Additionally, cases where 10 nodes or less (LND ≤10) or more than 10 nodes (LND > 10) were removed were analyzed separately. Adjuvant therapy was evaluated as radiotherapy, chemotherapy, or radiochemotherapy. Associations were analyzed by χ2 test, log-rank test, and Cox regression analysis. Overall survival (OS) had improved after total abdominal hysterectomy with bilateral salpingo-oophorectomy with LND > 10 (HR 0.62, 95% CI 0.47-0.83). Adjuvant therapy was related to OS with an HR of 0.64 (95% CI 0.54-0.75) for radiotherapy, an HR of 0.65 (95% CI 0.48-0.88) for chemotherapy, and an HR of 0.25 (95% CI 0.13-0.46) for radiochemotherapy. Additionally, adjuvant treatment was related to OS when lymph nodes were positive (HR 0.22, 95% CI 0.11-0.42), but not when they were negative. LND is related to improved survival when more than 10 nodes are removed. Adjuvant therapy improves survival when LND is omitted, or when nodes are positive. © 2018 S. Karger AG, Basel.

Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

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

Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au; University of Queensland, Brisbane; Foote, Matthew C.

Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapymore » because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.« less

Geographic Variation in the Use of Adjuvant Therapy among Elderly Patients with Resected Non-Small Cell Lung Cancer

PubMed Central

Tien, Yu-Yu; Wright, Kara; Halfdanarson, Thorvardur R.; Abu-Hejleh, Taher; Brooks, John M.

2016-01-01

Objectives The purpose of this study was to assess to what extent geographic variation in adjuvant treatment for non-small cell lung cancer (NSCLC) patients would remain, after controlling for patient and area-level characteristics. Materials and Methods A retrospective cohort of 18,410 Medicare beneficiaries with resected, stage I-IIIA NSCLC was identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Adjuvant therapies were classified as adjuvant chemotherapy (ACT), postoperative radiation therapy (PORT), or no adjuvant therapy. Predicted treatment probabilities were estimated for each patient given their clinical, demographic, and area-level characteristics with multivariate logistic regression. Area Treatment Ratios were used to estimate the propensity of patients in a local area to receive an adjuvant treatment, controlling for characteristics of patients in the area. Areas were categorized as low-, mid- and high-use and mapped for two representative SEER registries. Results Overall, 10%, 12%, and 78% of patients received ACT, PORT and no adjuvant therapy, respectively. Age, sex, stage, type and year of surgery, and comorbidity were associated with adjuvant treatment use. Even after adjusting for patient characteristics, substantial geographic treatment variation remained. High- and low-use areas were tightly juxtaposed within and across SEER registries, often within the same county. In some local areas, patients were up to eight times more likely to receive adjuvant therapy than expected, given their characteristics. On the other hand, almost a quarter of patients lived in local areas in which patients were more than three times less likely to receive ACT than would be predicted. Conclusion Controlling for patient and area-level covariates did not remove geographic variation in adjuvant therapies for resected NSCLC patients. A greater proportion of patients were treated less than expected, rather than more than expected

Effects of processing adjuvants on traditional Chinese herbs.

PubMed

Chen, Lin-Lin; Verpoorte, Robert; Yen, Hung-Rong; Peng, Wen-Huang; Cheng, Yung-Chi; Chao, Jung; Pao, Li-Heng

2018-04-01

Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs). Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs. Copyright © 2018. Published by Elsevier B.V.

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.

The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study.

PubMed

el-Darouti, M; Marzouk, S; Abdel Hay, R; el-Tawdy, A; Fawzy, M; Leheta, T; Gammaz, H; Al Gendy, N

2009-08-01

Pemphigus vulgaris (PV) represents a potentially life-threatening autoimmune blistering disease in which IgG autoantibodies are directed against cell-cell adhesion molecules. Tumour necrosis factor (TNF)-alpha has been suggested to have a possible role in the mechanism underlying acantholysis. This comparative double-blinded study was carried out to estimate the use of both sulfasalazine (SSZ) and pentoxifylline (PTX) (low-cost anti-TNF drugs) as an adjuvant therapy for PV. The study included 64 patients with PV: 42 patients received the full treatment regimen (with SSZ and PTX) and 22 patients followed the same regimen except they received placebo instead of PTX and SSZ. Five healthy subjects were included as controls. Serum samples were taken to measure TNF-alpha levels in the control group and before starting treatment in both the patient groups and this was repeated every 2 weeks for 8 weeks; a clinical assessment was made every week for all the patients. The serum level of TNF-alpha was statistically higher in both groups of patients than in the healthy individuals. There was a statistically significant decrease in the serum levels of TNF-alpha in patients in group 1 compared with those in group 2 at 6 and 8 weeks. There was also a significant clinical improvement in patients in group 1 compared with those in group 2. The use of PTX and SSZ as adjuvant therapy in the treatment of PV induced a faster and more significant decrease in the serum level of TNF-alpha, and this decrease was associated with rapid clinical improvement.

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

PubMed Central

Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

2016-01-01

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof. PMID:27818734

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs.

PubMed

Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin Cs; Peter, Aniekan I; Azu, Onyemaechi O

2016-10-01

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility ( P < 0.05) and count ( P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced ( P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant ( P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter ( P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

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

Krishnan, Sunil; Rana, Vishal; Evans, Douglas B.

2008-03-01

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies weremore » used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.« less

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

PubMed Central

2013-01-01

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

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

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late

Tamoxifen as the First Targeted Long Term Adjuvant Therapy for Breast Cancer

PubMed Central

Jordan, V. Craig

2014-01-01

Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, male breast cancer, pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that “longer was going to be better” when tamoxifen was being considered as an adjuvant therapy (Jordan 1978 Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen as a potential adjuvant therapy Reviews in Endocrine Related Cancer. October Supplement: 49–55.). This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. “Science is adventure, discovery, new horizons, insight into our world, a means of predicting the future and enormous power to help others”(Hoagland 1990).- Mahlon Hoagland, MD. Director, Worcester Foundation for Experimental Biology (1970–85) PMID:24659478

Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson s disease patients with motor complications.

PubMed

Stowe, Rebecca; Ives, Natalie; Clarke, Carl E; Deane, Katherine; Wheatley, Keith; Gray, Richard; Handley, Kelly; Furmston, Alex

2010-07-07

One of the complications of long-term treatment of Parkinson's disease (PD) with levodopa is the development of motor complications. Generally, when motor complications develop, clinicians add in an additional drug (to the levodopa regimen) from one of three other classes of anti-Parkinsonian treatments (dopamine agonists, catechol-O-methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs)). However, despite trials having shown that these drugs are beneficial compared to placebo, it remains unclear as to the best way to treat patients experiencing motor complications and whether one class of drug is more effective than another. This meta-analysis aims to assess more reliably the benefits and risks of the three classes of drugs (dopamine agonists, COMTIs and MAOBIs) currently used as adjuvant treatment to levodopa in PD patients suffering from motor complications. The three drug classes were compared with the aim of determining whether one class of drug provides better symptomatic control than another. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications. Randomised trials comparing an orally administered dopamine agonist, COMTI or MAOBI versus placebo, both on a background of levodopa therapy, in PD patients experiencing motor complications. Two authors independently extracted data on off-time, levodopa dose, motor complications, side-effects, treatment concordance, clinician-rated disability, mortality, quality of life and health economic data. Forty-four eligible trials, involving 8436 participants were identified. Compared to placebo, adjuvant therapy significantly reduced off-time (-1.05 hours/day, 95% confidence interval (CI) -1.19 to -0.90; P<0.00001), the required levodopa dose (-55.65 mg/day, CI -62.67 to -48.62; P<0.00001) and improved UPDRS scores (UPDRS ADL score

Update on PEG-interferon α-2b as adjuvant therapy in melanoma.

PubMed

Di Trolio, Rossella; Simeone, Ester; Di Lorenzo, Giuseppe; Grimaldi, Antonio Maria; Romano, Anna; Ayala, Fabrizio; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A

2012-09-01

Based on the results of European Organization for Research and Treatment of Cancer (EORTC) 18991 trial, the US Food and Drug Administration (FDA) approved PEG-interferon α-2b (PEG-IFN) (Sylatron) as adjuvant therapy for high-risk melanoma. The EORTC 18991 trial was an open-label study of resectable stage III melanoma with 1,256 patients who were randomized to observation-alone or to treatment with PEG-IFN for up to 5 years. The median recurrence-free survival of the treatment groups was significantly longer, while overall survival, a secondary endpoint, was not significantly different between the two groups. This review, after a short summary of interferon α-2b trials, critically analyzes the EORTC18991 trial, as well as the subgroup results and future perspectives for this stage of disease.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed

Korbelik, M; Naraparaju, V R; Yamamoto, N

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed Central

Korbelik, M.; Naraparaju, V. R.; Yamamoto, N.

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours. PMID:9010027

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

Altered Blood Flow Response to Small Muscle Mass Exercise in Cancer Survivors Treated With Adjuvant Therapy.

PubMed

Didier, Kaylin D; Ederer, Austin K; Reiter, Landon K; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher; Bemben, Michael G; Ade, Carl J

2017-02-07

Adjuvant cancer treatments have been shown to decrease cardiac function. In addition to changes in cardiovascular risk, there are several additional functional consequences including decreases in exercise capacity and increased incidence of cancer-related fatigue. However, the effects of adjuvant cancer treatment on peripheral vascular function during exercise in cancer survivors have not been well documented. We investigated the vascular responses to exercise in cancer survivors previously treated with adjuvant cancer therapies. Peripheral vascular responses were investigated in 11 cancer survivors previously treated with adjuvant cancer therapies (age 58±6 years, 34±30 months from diagnosis) and 9 healthy controls group matched for age, sex, and maximal voluntary contraction. A dynamic handgrip exercise test at 20% maximal voluntary contraction was performed with simultaneous measurements of forearm blood flow and mean arterial pressure. Forearm vascular conductance was calculated from forearm blood flow and mean arterial pressure. Left ventricular ejection time index (LVETi) was derived from the arterial pressure wave form. Forearm blood flow was attenuated in cancer therapies compared to control at 20% maximal voluntary contraction (189.8±53.8 vs 247.9±80.3 mL·min -1 , respectively). Forearm vascular conductance was not different between groups at rest or during exercise. Mean arterial pressure response to exercise was attenuated in cancer therapies compared to controls (107.8±10.8 vs 119.2±16.2 mm Hg). LEVTi was lower in cancer therapies compared to controls. These data suggest an attenuated exercise blood flow response in cancer survivors ≈34 months following adjuvant cancer therapy that may be attributed to an attenuated increase in mean arterial pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Antifungal adjuvants: Preserving and extending the antifungal arsenal

PubMed Central

Butts, Arielle; Palmer, Glen E.; Rogers, P. David

2017-01-01

ABSTRACT As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance. PMID:27459018

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

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.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

PubMed Central

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

2014-01-01

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

PubMed

Lecumberri, Elena; Dupertuis, Yves Marc; Miralbell, Raymond; Pichard, Claude

2013-12-01

Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Bisphosphonates as adjuvant therapy for breast cancer.

PubMed

Burkinshaw, Roger; Coleman, Robert

2006-01-01

Great strides have been made over the last 20 years in the treatment of breast cancer and despite an increasing incidence, the number of deaths has fallen sharply since the late 1980s. The advent of new therapies, including taxanes and aromatase inhibitors, and exciting results announced recently using trastuzumab in the adjuvant treatment of HER2-positive patients should decrease this even further. However, although most patients present with disease that appears to be localized to the breast, a significant proportion of women will eventually develop metastatic breast cancer. Therefore, the detection and treatment of micrometastatic disease represents perhaps the most important remaining challenge in breast cancer management, and is the focus of extensive ongoing research. Bone is the most frequent site of distant relapse, accounting for approximately 40% of all first recurrences. In addition to the well recognized release of bone cell-activating factors from the tumor, it is now appreciated that the release of bone-derived growth factors and cytokines from resorbing bone can attract cancer cells to the bone surface and facilitate their growth and proliferation. Bisphosphonates are potent inhibitors of bone osteolysis and the inhibition of bone resorption could therefore have an effect on the development and progression of metastatic bone disease. They could represent an adjuvant therapeutic strategy of potential importance. Clinical trial results with the early bisphosphonate, clodronate, have proved inconclusive. A large, randomized, controlled trial has recently completed accrual and should provide the definitive answer to the question of the role of clodronate in this setting. More potent second- and third-generation bisphosphonates have also shown enhanced antitumor effects in preclinical evaluation and further studies are required to determine whether this antitumor potential of bisphosphonates translates to the clinical setting. Adjuvant bisphosphonates are

Adjuvant Vascular Endothelial Growth Factor-targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis.

PubMed

Sun, Maxine; Marconi, Lorenzo; Eisen, Tim; Escudier, Bernard; Giles, Rachel H; Haas, Naomi B; Harshman, Lauren C; Quinn, David I; Larkin, James; Pal, Sumanta K; Powles, Thomas; Ryan, Christopher W; Sternberg, Cora N; Uzzo, Robert; Choueiri, Toni K; Bex, Axel

2018-05-18

Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC). To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC. A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed. We identified reports and reviewed them according to the Consolidated Standards of Reporting Trials and Standards for the Reporting of Diagnostic Accuracy Studies criteria. Of eight full-text articles that were eligible for inclusion, five studies (two of five were updated analyses) were retained in the final synthesis. Study characteristics were abstracted and the number needed to treat (NNT) per trial was estimated. The three randomized controlled phase III trials included the following comparisons: sunitinib versus placebo or sorafenib versus placebo (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma [ASSURE] study, n=1943), sunitinib versus placebo (S-TRAC, n=615), and pazopanib versus placebo (Pazopanib As Adjuvant Therapy in Localized/Locally Advanced RCC After Nephrectomy study, n=1135). The NNT ranged from 10 (S-TRAC) to 137 (ASSURE study). The pooled analysis showed that VEGFR-targeted therapy was not statistically significantly associated with improved DFS (hazard ratio [HR random ]: 0.92, 95% confidence interval [CI]: 0.82-1.03, p=0.16) or OS (HR random : 0.98, 95% CI: 0.84-1.15, p=0.84) compared with the control group. The adjuvant therapy group experienced significantly higher odds of grade 3-4 AEs (OR random : 5.89, 95% CI: 4.85-7.15, p<0.001). In exploratory analyses focusing on patients who started on the full

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

PubMed

Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

2017-08-01

Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

PubMed

Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

2017-08-01

Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

Transoral Resection of Human Papillomavirus (HPV)-Positive Squamous Cell Carcinoma of the Oropharynx: Outcomes with and Without Adjuvant Therapy.

PubMed

Jackson, Ryan S; Sinha, Parul; Zenga, Joseph; Kallogjeri, Dorina; Suko, Jasmina; Martin, Eliot; Moore, Eric J; Haughey, Bruce H

2017-11-01

With the rise of oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV), appropriate treatment strategies continue to be tailored toward minimizing treatment while preserving oncologic outcomes. This study aimed to compare the outcomes for those undergoing transoral resection with or without adjuvant therapy for HPV-related oropharyngeal carcinoma. A case-match cohort analysis was performed at two institutions on patients with HPV-related oropharyngeal squamous cell carcinoma. All the subjects underwent transoral surgery and neck dissection. The patients treated with surgery alone were matched 1:1 to those treated with surgery and adjuvant therapy using two groups identified as confounders: T-stage (T1/2 or T3/4) and number of pathologically positive lymph nodes (≤4 or >4). The study identified 105 matched pairs, with a median follow-up period of 42 months (range 3.1-102.3 months). The patients were staged as T1/T2 (86%) or T3/4 (14%). Each group had five patients with more than four positive lymph nodes. Adjuvant therapy significantly improved disease-free survival (hazard ratio [HR] 0.067; 95% confidence interval [CI] 0.01-0.62) and was associated with a lower risk of local and regional recurrence (risk ratio [RR] 0.096; 95% CI 0.02-0.47). No difference in disease-specific survival (HR 0.22; 95% CI 0.02-2.57) or overall survival (HR 0.18; 95% CI 0.01-2.4) was observed with the addition of adjuvant therapy. The risk of the gastrostomy tube was higher for those receiving adjuvant therapy (RR 7.3; 95% CI 2.6-20.6). Transoral surgery is an effective approach for the treatment of HPV-related oropharyngeal carcinoma. The addition of adjuvant therapy appears to decrease the risk of recurrence and improve disease-free survival but may not significantly improve overall survival.

Mapping the Decision-Making Process for Adjuvant Endocrine Therapy for Breast Cancer: The Role of Decisional Resolve.

PubMed

Beryl, Louise L; Rendle, Katharine A S; Halley, Meghan C; Gillespie, Katherine A; May, Suepattra G; Glover, Jennifer; Yu, Peter; Chattopadhyay, Runi; Frosch, Dominick L

2017-01-01

Studies show adjuvant endocrine therapy increases survival and decreases risk of breast cancer recurrence for hormone receptor-positive tumors. Yet studies also suggest that adherence rates among women taking this therapy may be as low as 50% owing largely to adverse side effects. Despite these rates, research on longitudinal patient decision making regarding this therapy is scant. We sought to map the decision-making process for women considering and initiating adjuvant endocrine therapy, paying particular attention to patterns of uncertainty and decisional change over time. A longitudinal series of semistructured interviews conducted at a multispecialty health care organization in Northern California with 35 newly diagnosed patients eligible for adjuvant endocrine therapy were analyzed. Analysis led to the identification and indexing of 3 new decision-making constructs-decisional phase, decisional direction, and decisional resolve-which were then organized using a visual matrix and examined for patterns characterizing the decision-making process. Our data reveal that most patients do not make a single, discrete decision to take or not take hormone therapy but rather traverse multiple decisional states, characterized by 1) phase, 2) direction, and 3) strength of resolve. Our analysis tracks these decisional states longitudinally using a grayscale-coded matrix. Our data show that decisional resolve wavers not just when considering therapy, as the existing concept of decisional conflict suggests, but even after initiating it, which may signal future decisions to forgo therapy. Adjuvant endocrine therapy, like other chronic care decisions, has a longer decision-making process and implementation period. Thus, theoretical, empirical, and clinical approaches should consider further exploring the new concept and measurement of decisional resolve, as it may help to improve subsequent medication adherence. © The Author(s) 2016.

Adjuvant radiation therapy and survival for adenoid cystic carcinoma of the breast.

PubMed

Sun, Jia-Yuan; Wu, San-Gang; Chen, Shan-Yu; Li, Feng-Yan; Lin, Huan-Xin; Chen, Yong-Xiong; He, Zhen-Yu

2017-02-01

The assess the clinical value of different types of surgical procedures and further analyze the effect of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast. Patients with ACC of the breast were identified using a population-based national registration database (Surveillance, Epidemiology, and End Results, SEER). The Kaplan-Meier method and Cox regression models were performed to determine the impact of the surgical procedures and adjuvant RT associated with cause-specific survival (CSS) and overall survival (OS). A total of 478 patients with ACC of the breast were identified. The median follow-up was 59 months. The 10-year CSS and OS were 87.5% and 75.3%, respectively. For the Kaplan-Meier analysis, the 5-year CSS were 96.1%, 91.8%, 90.2%, and 94.1% in patients that received lumpectomy + adjuvant RT, lumpectomy alone, mastectomy alone, and mastectomy + adjuvant RT, respectively (p = 0.026). In the multivariate Cox analyses, lumpectomy + adjuvant RT was an independent prognostic factor for CSS and OS. Patients that received lumpectomy + adjuvant RT had better survival rates than patients that underwent lumpectomy only (CSS, p = 0.018; OS, p = 0.031) and mastectomy only (CSS, p = 0.010; OS, p = 0.004). ACC of the breast has an excellent prognosis. Breast-conserving surgery is a reasonable alternative for patients with ACC of the breast, and adjuvant RT after lumpectomy improved survival rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

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

Valicenti, Richard K., E-mail: Richard.valicenti@ucdmc.ucdavis.edu; Thompson, Ian; Albertsen, Peter

Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemicalmore » recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.« less

Comparative survival analysis of adjuvant therapy with iodine-131-labeled lipiodol to hepatic resection of primary hepatocellular carcinoma: a meta-analysis.

PubMed

Gong, Lin; Shi, Lu; Sun, Jing; Yuan, Wei-Sheng; Chen, Jian-Feng; Liu, Peng; Gong, Feng; Dong, Jia-Hong

2014-05-01

Adjuvant therapies play an important role in delaying the recurrence of hepatocellular carcinoma (HCC) in patients with resectable tumor. Among the available options, use of radionuclides is an effective strategy. This meta-analysis aims to examine the evidence pertaining to the effectiveness of adjuvant therapy with intra-arterial iodine-131-labeled lipiodol ((131)I-lipiodol) to hepatic resection of HCC. A literature survey was conducted of multiple electronic databases including PubMed/Medline, Embase, CINAHL, Cochrane library, and Google Scholar using various combinations of the most relevant key terms. The odds ratio-based meta-analysis of recurrence and survival rates was performed with RevMan software (version 5.2) using a random-effect model. Heterogeneity was assessed by χ(2) and I(2) statistics. When compared with the resection-only group, recurrence rates at 2 and 5 years were significantly lower in patients who received adjuvant therapy with intra-arterial I-lipiodol, with a corresponding odds ratio (95% confidence interval) of 0.45 (0.29-0.70) and 0.52 (0.32-0.85), respectively. The 3- and 5-year overall survival rates were found to be significantly higher in patients who received adjuvant therapy with (131)I-lipiodol than in patients who were not given any adjuvant therapy. Between-study statistical heterogeneity was moderate. Postoperative adjuvant therapy with intra-arterial (131)I-lipiodol to hepatic resection of HCC significantly improves overall and disease-free survival rates and reduces recurrence rates. However, well-designed randomized trials are needed to arrive at conclusive evidence.

Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision

PubMed Central

2013-01-01

Background There is uncertainty on the benefit of adjuvant chemotherapy in patients with stage II colorectal cancers. The aim of this study is to investigate the combined role of clinical, pathological and molecular parameters to identify those stage II patients who better benefit from adjuvant therapy. Methods We examined 120 stage II colon cancer patients. Of these, 60 patients received adjuvant 5-FU chemotherapy after surgery and the other 60 did not receive therapy. Immunohistochemical (IHC) analyses were performed to evaluate the expressions of Thymidylate synthetase (TYMS), TP53 (p53), β-catenin (CTNNB1) and CD8. For TYMS, its mRNA expression levels were also investigated by real time qRT-PCR. The entire case study was characterized by the presence of a defect in the MMR (mismatch repair) system, the presence of the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRAF gene. At the histo-pathological level, the depth of tumour invasion, lymphovascular invasion, invasion of large veins, host lymphocytic response and tumour border configuration were recorded. Results The presence of the V600E mutation in the BRAF gene was a poor prognostic factor for disease free and overall survival (DFS; hazard ratio [HR], 2.57; 95% CI: 1.03 -6.37; p = 0.04 and OS; HR, 3.68; 95% CI: 1.43-9.47; p < 0.01 respectively), independently of 5-FU treatment. Adjuvant therapy significantly improved survival in patients with high TYMS levels (p = 0.04), while patients with low TYMS had a better outcome if treated by surgery alone (DFS; HR, 6.07; 95% CI, 0.82 to 44.89; p = 0.04). In patients with a defect in the MMR system (dMMR), 5-FU therapy was associated to reduced survival (DFS; HR, 37.98; 95% CI, 1.04 to 1381.31; p = 0.04), while it was beneficial for CIMP-High associated tumours (DFS; HR, 0.17; 95% CI, 0.02 to 1.13; p = 0.05). Conclusions Patients’ characterization according to MMR status, CIMP phenotype and TYMS m

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

Does estrogen play a role in response to adjuvant bone-targeted therapies?

PubMed Central

Russell, Kent; Amir, Eitan; Paterson, Alexander; Josse, Robert; Addison, Christina; Kuchuk, Iryna; Clemons, Mark

2013-01-01

Bone remains the most common site of breast cancer recurrence. The results of population studies, pre-clinical research and clinical studies in patients with metastatic disease provided a rationale for testing bone-targeted agents in the adjuvant setting. Despite the initial optimism, results from eight prospectively designed, randomized control studies powered to assess the value of adjuvant bone-targeted therapy in early breast cancer are conflicting. Data have shown that, where benefit exists, it tends to be in women with a “low estrogen environment”, either through menopause or suppression of ovarian function. In this manuscript, we review clinical data supporting the hypothesis that estrogen levels may play a part in explaining the response of patients to bone-targeted agents in the adjuvant setting. The results presented to date suggest that there may be data supporting a unifying role for estrogen in adjuvant trials. However, in the absence of any prospective randomized trials in which estrogen data has been systematically collected we cannot specifically answer this question. We await the results of the Oxford overview analysis of individual patient data with interest. PMID:26909288

Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

PubMed

Miladi, Imen; Vivier, Magali; Dauplat, Marie-Mélanie; Chatard, Morgane; Besse, Sophie; Vidal, Aurélien; Chassain, Karine; Jean, Betty; Forestier, Christiane; Chezal, Jean-Michel; Rédini, Francoise; Degoul, Francoise; Miot-Noirault, Elisabeth

2017-09-01

This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management.

Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy.

PubMed

Farace, Paolo; Amelio, Dante; Ricciardi, Giuseppe K; Zoccatelli, Giada; Magon, Stefano; Pizzini, Francesca; Alessandrini, Franco; Sbarbati, Andrea; Amichetti, Maurizio; Beltramello, Alberto

2013-01-01

To investigate the increase in MRI contrast enhancement (CE) occurring in glioblastoma during the period between surgery and initiation of chemo-radiotherapy, thirty-seven patients with newly diagnosed glioblastoma were analyzed by early post-operative magnetic resonance (EPMR) imaging within three days of surgery and by pre-adjuvant magnetic resonance (PAMR) examination before adjuvant therapy. Areas of new CE were investigated by use of EPMR diffusion-weighted imaging and PAMR perfusion imaging (by arterial spin-labeling). PAMR was acquired, on average, 29.9 days later than EPMR (range 20-37 days). During this period an increased area of CE was observed for 17/37 patients. For 3/17 patients these regions were confined to areas of reduced EPMR diffusion, suggesting postsurgical infarct. For the other 14/17 patients, these areas suggested progression. For 11/17 patients the co-occurrence of hyperperfusion in PAMR perfusion suggested progression. PAMR perfusion and EPMR diffusion did not give consistent results for 3/17 patients for whom small new areas of CE were observed, presumably because of the poor spatial resolution of perfusion imaging. Before initiation of adjuvant therapy, areas of new CE of resected glioblastomas are frequently observed. Most of these suggest tumor progression, according to EPMR diffusion and PAMR perfusion criteria.

Adherence to adjuvant endocrine therapy: is it a factor for ethnic differences in breast cancer outcomes in New Zealand?

PubMed

Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Kuper-Hommel, Marion; Kim, Boa; Pillai, Avinesh; Lawrenson, Ross

2015-02-01

Despite the benefits of adjuvant endocrine therapy for hormone receptor positive breast cancer, many women are non-adherent or discontinue endocrine treatment early. We studied differences in adherence to adjuvant endocrine therapy by ethnicity in a cohort of New Zealand women with breast cancer and its impact on breast cancer outcomes. We analysed data on women (n = 1149) with newly diagnosed hormone receptor positive, non-metastatic, invasive breast cancer who were treated with adjuvant endocrine therapy in the Waikato during 2005-2011. Linked data from the Waikato Breast Cancer Registry and National Pharmaceutical Database were examined to identify differences by ethnicity in adherence to adjuvant endocrine therapy and the effect of sub-optimal adherence on cancer recurrence and mortality. Overall, a high level of adherence of ≥80% was observed among 70.4% of women, which declined from 76.8% to 59.3% from the first to fifth year of treatment. Māori women were significantly more likely to be sub-optimally adherent (<80%) compared with European women (crude rate 37% vs. 28%, p = 0.005, adjusted OR = 1.51, 95% CI 1.04-2.17). Sub-optimal adherence was associated with a significantly higher risk of breast cancer mortality (HR = 1.77, 95% CI 1.05-2.99) and recurrence (HR = 2.14, 95% CI 1.46-3.14). Sub-optimal adherence to adjuvant endocrine therapy was a likely contributor for breast cancer mortality inequity between Māori and European women, and highlights the need for future research to identify effective ways to increase adherence in Māori women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain.

PubMed

Aronson, M D

1997-01-01

The treatment of chronic pain is an important function of physicians. In the United States, available drug treatments for chronic pain currently include simple analgesics such as acetaminophen, salicylates and other nonsteroidal anti-inflammatory drugs, traditional opioid drugs, and adjuvant agents (eg, antidepressants, anticonvulsants). Typically, the choice of a drug is made by balancing the indications for treatment, the clinical efficacy of the drug, and its toxicity. An understanding of the mechanism of action of these drugs helps to establish their role in therapy. Tramadol is an effective analgesic that works through a combined mechanism of weak mu receptor binding and the inhibition of serotonin and norepinephrine reuptake. Tramadol has a favorable adverse-effect profile and therefore is likely to have an important role in the management of chronic pain syndromes.

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

A Multidisciplinary Patient Navigation Program Improves Compliance With Adjuvant Breast Cancer Therapy in a Public Hospital.

PubMed

Castaldi, Maria; Safadjou, Saman; Elrafei, Tarek; McNelis, John

Cancer health disparities affecting low-income and minority patients have been well documented to lead to poor outcomes. This report examines the impact of patient navigation on adherence to prescribed adjuvant breast cancer treatment. A multidisciplinary patient navigation program was initiated at a public safety net hospital to improve compliance with 3 National Quality Forum measures: (1) administration of combination chemotherapy for women with Stage (defined by the American Joint Committee on Cancer [AJCC]) T1c, II, or III hormone receptor-negative breast cancer within 120 days; (2) administration of endocrine therapy for women with AJCC Stage T1c, II, or III hormone receptor-positive breast cancer within 365 days; and (3) radiation therapy for women receiving breast-conserving surgery within one year. Implementation of a multidisciplinary patient navigation program reduced time to treatment and improved compliance with adjuvant therapy for breast cancer in an underserved minority community.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

PubMed

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

PubMed Central

Bowden, Mark G.; Embry, Aaron E.; Gregory, Chris M.

2011-01-01

Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s) to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s) will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1) walking specific motor control; (2) dynamic balance; (3) cardiorespiratory fitness and (4) muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance. PMID:22013549

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

PubMed Central

de Oliveira, Leandro Licursi; Coltri, Kely Cristine; Cardoso, Cristina Ribeiro Barros; Roque-Barreira, Maria-Cristina; Panunto-Castelo, Ademilson

2008-01-01

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. PMID:18335066

21 CFR 182.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 182.99 Section 182.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182.99 Adjuvants for pesticide chemicals...

Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

PubMed

Zhu, Xin Yan; Liu, Fei

2017-04-01

Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

PubMed Central

Gill, Erin E; Franco, Octavio L; Hancock, Robert E W

2015-01-01

The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era. PMID:25393203

Combined influence of adjuvant therapy and interval after surgery on peripheral CD4+ T lymphocytes in patients with esophageal squamous cell carcinoma

PubMed Central

LING, YANG; FAN, LIEYING; DONG, CHUNLEI; ZHU, JING; LIU, YONGPING; NI, YAN; ZHU, CHANGTAI; ZHANG, CHANGSONG

2010-01-01

The aim of this study was to investigate possible differences in cellular immunity between chemo- and/or radiotherapy groups during a long interval after surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT), radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood samples obtained at different time points relative to surgery from 73 patients with ESCC. The changes in the absolute and relative proportions of lymphocyte phenotypes were significant among the adjuvant therapy groups. There were significant differences in the absolute counts of CD4+ and CD8+ T cells among the interval groups, and a lower CD4/CD8 ratio was found in patients following a prolonged interval. RT alone had a profound effect on the absolute counts of CD3+, CD4+ and CD8+ T cells compared with the other groups. CD4+ T cells exhibited a decreasing trend during a long interval, leading to a prolonged T-cell imbalance after surgery. Univariate analysis revealed that the interaction of the type of adjuvant therapy and the interval after surgery was correlated only with the percentage of CD4+ T cells. The percentage of CD4+ T cells can be used as an indicator of the cellular immunity after surgery in ESCC patients. However, natural killer cells consistently remained suppressed in ESCC patients following adjuvant therapy after surgery. These findings confirm an interaction between adjuvant therapy and the interval after surgery on peripheral CD4+ T cells, and implies that adjuvant therapy may have selective influence on the cellular immunity of ESCC patients after surgery. PMID:23136603

The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea

PubMed Central

Kim, Young Suk; Choi, Jae Hyuck; Kim, Kwang Sik; Lim, Gil Chae; Kim, Jeong Hong; Kang, Ju Wan; Song, Hee-Sung; Lee, Sang Ah; Hyun, Chang Lim; Choi, Yunseon; Kim, Gwi Eon

2017-01-01

Purpose To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Materials and Methods Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). Results The age range was 26–87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Conclusion Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients. PMID:28712279

Spinal cord gliomas: management and outcome with reference to adjuvant therapy.

PubMed

Nishio, S; Morioka, T; Fujii, K; Inamura, T; Fukui, M

2000-01-01

The authors review their experience with 19 consecutive cases with either astrocytic tumour (glioblastoma multiforme one, anaplastic astrocytoma one, astrocytoma 4, pilocytic astrocytoma 4) or ependymoma (10 tumours in 9 patients) of the spinal cord who were treated during the period from 1982 to 1996. The patients included 10 male and 9 female patients with a median age of 38 years. The main tumour locations included the cervicomedullary region 5 the cervical cord (8), the thoracic cord (5) and one each in the thoracolumbar region and conus medullaris. While a total removal of the tumour was achieved in 8 out of 10 ependymomas, the initial treatment for astrocytic tumours was a partial resection in 5, and biopsy in the remaining 5. As adjuvant treatment, 8 patients received radiation therapy and 2 received chemotherapy. Two patients with an astrocytic tumour received chemotherapy only, while the remaining 9 received neither radiation therapy nor chemotherapy initially. After these treatments, 6 out of the 8 patients with low grade astrocytoma have remained alive for 1.3-12.6 years, while 2 patients with high grade astrocytic tumours died within 15 months following surgery. Eight out of 9 patients with an ependymoma have remained alive for 3.0-12.3 years, while one committed suicide 2 years after surgery. As a result, 14 patients are still alive; half of them are accompanied by a mild neurological dysfunction, while the remaining one has a moderate deficit. The postoperative results and the rationale for surgery is discussed, and an approach for utilising adjuvant therapy for high grade tumours is also suggested.

Use of trastuzumab as an adjuvant/neoadjuvant therapy in patients with HER2-positive breast cancer in China: The Nvwa study.

PubMed

Li, Junjie; Shao, Zhimin; Xu, Binghe; Jiang, Zefei; Cui, Shude; Zhang, Jin; Liao, Ning; Jiang, Jun; Wang, Yongsheng; Ouyang, Quchang; Ying, Ziwei

2018-05-01

The aim of this study was to understand current trends in trastuzumab use in China as a neoadjuvant/adjuvant therapy for human epidermal growth factor receptor-2 positive (HER2+) breast cancer and identify factors influencing trastuzumab use.This was a retrospective, multicenter, cross-sectional study of patients diagnosed with HER2+ breast cancer (stage I-III), between July 2013 and June 2014, at 155 hospitals in 29 provinces/cities in China. Demographic and clinical data, including tumor characteristics and details of adjuvant/neoadjuvant therapies used, were collected. Data analysis included univariate analysis, multivariate logistic regression, and subgroup analyses.Of 4994 HER2+ patients (mean age 51.1 ± 9.9 years) included, only 29.8% received trastuzumab, with 30.5% in adjuvant therapy and 18.3% in neoadjuvant therapy. The highest rates of adjuvant trastuzumab were in Beijing (59.3%), Jiangsu (57.1%), and Ningxia (50.0%), while those of neoadjuvant trastuzumab were in Guangdong (24.8%), Beijing (14.1%), and Zhejiang (10.7%). Multivariate regression results revealed that factors associated with trastuzumab use were medical insurance cover for trastuzumab, residing locally to the hospital, more lymph node involvement, and more advanced tumor stage. Subgroup analysis revealed that patients receiving neoadjuvant therapy were likely to be younger, premenopausal and non-local, and had lymph node metastases, more advanced tumor, and progesterone receptor positive tumor.Trastuzumab use in patients with HER2+ breast cancer is relatively low in China, especially for neoadjuvant therapy. Insurance coverage seems to be the most correlated factor that influences the use of trastuzumab in Chinese patients with HER2+ breast cancer.

Gold glyconanoparticles coupled to listeriolysin O 91-99 peptide serve as adjuvant therapy against melanoma.

PubMed

Calderon-Gonzalez, R; Terán-Navarro, H; García, I; Marradi, M; Salcines-Cuevas, D; Yañez-Diaz, S; Solis-Angulo, A; Frande-Cabanes, E; Fariñas, M C; Garcia-Castaño, A; Gomez-Roman, J; Penades, S; Rivera, F; Freire, J; Álvarez-Domínguez, C

2017-08-03

Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO 91-99 ), which acts as a novel adjuvant for cancer therapy. GNP-LLO 91-99 , when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients. GNP-LLO 91-99 nanoparticles caused tumour apoptosis and induced antigen- and melanoma-specific cytotoxic Th1 responses (P ≤ 0.5). We propose this adjuvant nanotherapy for preventing the progression of the first stages of melanoma.

21 CFR 172.710 - Adjuvants for pesticide use dilutions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Adjuvants for pesticide use dilutions. 172.710 Section 172.710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The...

21 CFR 172.710 - Adjuvants for pesticide use dilutions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Adjuvants for pesticide use dilutions. 172.710 Section 172.710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The...

[Organ-limited prostate cancer with positive resection margins. Importance of adjuvant radiation therapy].

PubMed

Porres, D; Pfister, D; Brehmer, B; Heidenreich, A

2012-09-01

For pT3 prostate cancer with positive resection margins, the importance of postoperative radiation therapy is confirmed by a high level of evidence. However, for the pT2,R1 situation prospective, randomized studies concerning this question are lacking. Despite better local tumor control in the pT2 stage the PSA recurrence rate lies between 25% and 40% and positive margins are an independent factor for recurrence. Retrospective studies suggest a positive effect of adjuvant or salvage radiation for the oncological outcome in the pT2,R1 situation. On the other hand the side effects profile, with a potentially negative influence of postoperative continence and various delayed toxicities, is not insignificant despite modern radiation techniques and in the era of ultrasensitive PSA analysis should be considered in the risk-benefit assessment. As long as the optimal initiation of postoperative radiation therapy is unclear, the assessment of indications for adjuvant or salvage radiation for organ-limited prostate cancer with positive resection margins should be made after an individual patient consultation and under consideration of the recurrence risk factors, such as the Gleason grade and the localization and extent of the resection margins.

Multivariate analysis of prognostic factors for idiopathic sudden sensorineural hearing loss treated with adjuvant hyperbaric oxygen therapy.

PubMed

Xie, Shaobing; Qiang, Qingfen; Mei, Lingyun; He, Chufeng; Feng, Yong; Sun, Hong; Wu, Xuewen

2018-01-01

The objective of this study is to evaluate possible prognostic factors of idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT) using univariate and multivariate analyses. From January 2008 to October 2016, records of 178 ISSNHL patients treated with auxiliary hyperbaric oxygen therapy were reviewed to assess hearing recovery and evaluate associated prognostic factors (gender, age, localization, initial hearing threshold, presence of tinnitus, vertigo, ear fullness, hypertension, diabetes, onset of HBOT, number of HBOT, and audiogram), by using univariate and multivariate analyses. The overall recovery rate was 37.1%, including complete recovery (19.7%) and partial recovery (17.4%). According to multivariate analysis, later onset of HBOT and higher initial hearing threshold were associated with a poor prognosis in ISSNHL patients treated with HBOT. HBOT is a safe and beneficial adjuvant therapy for ISSNHL patients. 20 sessions of HBOT is possibly enough to show its therapeutic effect. Earlier HBOT onset and lower initial hearing threshold is associated with favorable hearing recovery.

The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients.

PubMed

Chen, Michelle M; Roman, Sanziana A; Sosa, Julie A; Judson, Benjamin L

2015-02-01

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm that most commonly occurs in the head and neck and is rapidly increasing in incidence. The role of adjuvant chemoradiotherapy (CRT) in the management of head and neck MCC remains controversial. To evaluate the association between different adjuvant therapies and survival in head and neck MCC. Retrospective review of adult patients with head and neck MCC who had surgery recorded in the National Cancer Data Base from 1998 to 2011. Surgical excision, adjuvant radiation therapy (RT), or adjuvant CRT. Our main outcome was overall survival (OS). Statistical analysis included χ2, t tests, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. We identified 4815 patients; 92.0% underwent standard surgical excision, and 8.0% underwent Mohs surgery. On multivariate analysis, age at least 75 years (hazard ratio [HR], 2.83 [95% CI, 1.82-4.41]), larger tumor size, positive margins (HR, 1.52 [95% CI, 1.25-1.85]), and metastatic lymph nodes (HR, 2.29 [95% CI, 1.84-2.85]) were independently associated with decreased OS. Postoperative CRT (HR, 0.62 [95% CI, 0.47-0.81]) and RT (HR, 0.80 [95% CI, 0.70-0.92]) provided a survival benefit over surgery alone. Adjuvant CRT was associated with improved OS over adjuvant RT in patients with positive margins (HR, 0.48 [95% CI, 0.25-0.93]), tumor size at least 3 cm (HR, 0.52 [95% CI, 0.30-0.90]), and male sex (HR, 0.69 [95% CI, 0.50-0.94]). To our knowledge, this the first study examining the role of adjuvant CRT in head and neck MCC. Results suggest that adjuvant CRT may help improve survival in high-risk patients, such as males and those with positive margins and larger tumors.

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

TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas

PubMed Central

Ding, Xiao-Jie; Qin, Zhi-Yong; Hong, Christopher S.; Chen, Ling-Chao; Zhang, Xin; Zhao, Fang-Ping; Wang, Yin; Wang, Yang; Zhou, Liang-Fu; Zhuang, Zhengping; Ng, Ho-Keung; Yan, Hai; Yao, Yu; Mao, Ying

2015-01-01

IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p < 0.001) were independent prognostic factors for PFS and OS in patients receiving genotoxic therapies while TERT promoter mutations were not. In univariate analysis, IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery

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.

Combination Approaches to Combat Multi-Drug Resistant Bacteria

PubMed Central

Worthington, Roberta J.; Melander, Christian

2013-01-01

The increasing prevalence of infections caused by multi-drug resistant bacteria is a global health problem that is exacerbated by the dearth of novel classes of antibiotics entering the clinic over the past 40 years. Herein we describe recent developments toward combination therapies for the treatment of multi-drug resistant bacterial infections. These efforts include antibiotic-antibiotic combinations, and the development of adjuvants that either directly target resistance mechanisms such as the inhibition of β-lactamase enzymes, or indirectly target resistance by interfering with bacterial signaling pathways such as two-component systems. We also discuss screening of libraries of previously approved drugs to identify non-obvious antimicrobial adjuvants. PMID:23333434

Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

PubMed Central

Chandran, Sindhu; Vagefi, Parsia A.

2014-01-01

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. PMID:25349720

Adjuvant radiation therapy and lymphadenectomy in esophageal cancer: a SEER database analysis.

PubMed

Shridhar, Ravi; Weber, Jill; Hoffe, Sarah E; Almhanna, Khaldoun; Karl, Richard; Meredith, Kenneth

2013-08-01

This study seeks to determine the effects of postoperative radiation therapy and lymphadenectomy on survival in esophageal cancer. An analysis of patients with surgically resected esophageal cancer from the SEER database between 2004 and 2008 was performed to determine association of adjuvant radiation and lymph node dissection on survival. Survival curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. We identified 2109 patients who met inclusion criteria. Radiation was associated with increased survival in stage III patients (p = 0.005), no benefit in stage II (p = 0.075) and IV (p = 0.913) patients, and decreased survival in stage I patients (p < 0.0001). Univariate analysis revealed that radiation therapy was associated with a survival benefit node positive (N1) patients while it was associated with a detriment in survival for node negative (N0) patients. Removing >12 and >15 lymph nodes was associated with increased survival in N0 patients, while removing >8, >10, >12, >15, and >20 lymph nodes was associated with a survival benefit in N1 patients. MVA revealed that age, gender, tumor and nodal stage, tumor location, and number of lymph nodes removed were prognostic for survival in N0 patients. In N1 patients, MVA showed the age, tumor stage, number of lymph nodes removed, and radiation were prognostic for survival. The number of lymph nodes removed in esophageal cancer is associated with increased survival. The benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to N1 patients.

Multiple cardiac complications after adjuvant therapy for breast cancer: the importance of echocardiography. A case report and review of the literature.

PubMed

Gurghean, Adriana Luminita; Savulescu-Fiedler, Ilinca; Mihailescu, Anca

2017-01-31

Cardiovascular complications induced by adjuvant cancer therapies may become symptomatic after many years, being responsible for increased morbidity and mortality in long-term survivors. We report a case of a 54-year old female admitted for severe heart failure induced by myocardial and valvular damage after postoperative adjuvant therapy for left breast cancer 6 years ago. Her recent history revealed nonST elevation myocardial infarction in the absence of significant cardiovascular risk factors. Transthoracic echocardiography, tissue Doppler imaging and speckle-tracking imaging revealed severe biventricular systolic dysfunction, severe mitral and tricuspid regurgitation and severe pulmonary hypertension.

Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

PubMed

Bennett, Marsha; Bonanno, Laura; Kuhn, William

2016-10-01

The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

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.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

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

Strauss, Joshua; Hershman, Dawn L.; Department of Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY

2010-04-15

Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combinedmore » chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.« less

Adjuvant psychological therapy in long-term endocrine conditions.

PubMed

Daniels, J; Turner-Cobb, J M

2017-06-01

Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome. © 2017 John Wiley & Sons Ltd.

Biosafe Nanoscale Pharmaceutical Adjuvant Materials

PubMed Central

Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

2014-01-01

Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women.

PubMed

Rossi, Lorenzo; Pagani, Olivia

2017-05-01

In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

PubMed Central

Munoz, Diego; Near, Aimee M.; van Ravesteyn, Nicolien T.; Lee, Sandra J.; Schechter, Clyde B.; Alagoz, Oguzhan; Berry, Donald A.; Burnside, Elizabeth S.; Chang, Yaojen; Chisholm, Gary; de Koning, Harry J.; Ali Ergun, Mehmet; Heijnsdijk, Eveline A. M.; Huang, Hui; Stout, Natasha K.; Sprague, Brian L.; Trentham-Dietz, Amy; Mandelblatt, Jeanne S.

2014-01-01

Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13–21) and 5 per 100000 women (model range = 3–6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%–87.8% vs 85.7%–96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. PMID:25255803

Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy.

PubMed

Bakhsh, Salwa; Kinloch, Mary; Hoang, Lien N; Soslow, Robert A; Köbel, Martin; Lee, Cheng-Han; McAlpine, Jessica N; McConechy, Melissa K; Gilks, C Blake

2016-05-01

To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations. Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype. POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy. © 2015 John Wiley & Sons Ltd.

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

NASA Astrophysics Data System (ADS)

Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p < 0.2). In the definitive radiation group, overall survival at years one, two, and three were 96%, 92%, and 92%, respectively. A hemoglobin (Hb) level >12 g/dl was a factor with an average association with the overall survival (p < 0.2). The differences between both groups of therapy were not statistically significant (92% vs. 93.3%; p = 0.138). This study did not show any statistically significant overall survival for cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

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.

Obesity drug therapy.

PubMed

Baretić, M

2013-09-01

Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question.

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

Activity of glycated chitosan and other adjuvants to PDT vaccines

NASA Astrophysics Data System (ADS)

Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

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.

The role of revision surgery and adjuvant therapy following subtotal resection of osteosarcoma of the spine: a systematic review with meta-analysis.

PubMed

Shankar, Ganesh M; Clarke, Michelle J; Ailon, Tamir; Rhines, Laurence D; Patel, Shreyaskumar R; Sahgal, Arjun; Laufer, Ilya; Chou, Dean; Bilsky, Mark H; Sciubba, Daniel M; Fehlings, Michael G; Fisher, Charles G; Gokaslan, Ziya L; Shin, John H

2017-07-01

OBJECTIVE Primary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved. METHODS A systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis. RESULTS A total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06). CONCLUSIONS While the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

PubMed Central

Yιlmaz, Defne; Phipps, Colin; Kohandel, Mohammad

2017-01-01

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor. PMID:28922358

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.

PubMed

Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad

2017-09-01

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

Does lifetime exposure to hormones predict pretreatment cognitive function in women before adjuvant therapy for breast cancer?

PubMed Central

Bender, Catherine M.; Sereika, Susan M.; Ryan, Christopher M.; Brufsky, Adam M.; Puhalla, Shannon; Berga, Sarah L.

2013-01-01

Objective Women with breast cancer have been found to have poorer cognitive function before the initiation of systemic adjuvant therapy than their age- and education-matched counterparts. The basis for this may partly include hormone exposure during the course of a woman’s life. Methods We compared cognitive function between postmenopausal women with breast cancer before the initiation of systemic adjuvant therapy and healthy age- and education-matched postmenopausal women and examined whether factors related to lifetime exposure to hormones predicted cognitive function before therapy. Results We found that, compared with healthy women, women with breast cancer had poorer memory (P = 0.05) and attention (P = 0.006). Controlling for the covariates age and estimated verbal intelligence, we found that factors related to greater lifetime hormone exposure (oral contraceptive use, greater years since menopause, and longer duration of hormone therapy) predicted cognitive function (executive function, verbal learning and memory, attention, psychomotor efficiency, and visual sustained attention) in women with and without breast cancer but did not explain the differences in cognitive function observed at pretreatment in women with breast cancer. Conclusions Other factors may explain the poorer pretreatment cognitive function in women with breast cancer, including persistent effects of surgical operation and anesthesia, sleep problems, and tumor-related factors. Additional studies are needed to explicate the basis of poorer pretherapy cognitive function in this population. PMID:23481123

[Combination drug therapy in leprosy].

PubMed

Terencio de las Aguas, J

1983-01-01

The importance of polichemotherapy in multibacilar leprosy (LL and LD) in patients without any previous therapy as in those diagnosticated and under monotherapy most of all in the resistance patients is presented. Sulphones, clofazimine and rifampicine are selected as first rate drugs and protionamide-etionamide as second rate drugs. The therapy plans with the association of two and three drugs and the convenience of continuing indefinitely with at least one of the drugs are presented insisting on the advantages of the clofazimine-sulphones and rifampicine-sulphones associations. The necessity of immunotherapy for recover of celular immunity against the bacilus, is the only form of preventing relapses and drug resistance.

Drug interactions between common illicit drugs and prescription therapies.

PubMed

Lindsey, Wesley T; Stewart, David; Childress, Darrell

2012-07-01

The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

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.

Drug Delivery in Cancer Therapy, Quo Vadis?

PubMed

Lu, Zheng-Rong; Qiao, Peter

2018-03-22

The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

PubMed

Yamazaki, Naoya; Uhara, Hisashi; Wada, Hidefumi; Matsuda, Kenji; Yamamoto, Keiko; Shimamoto, Takashi; Kiyohara, Yoshio

2016-10-01

In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial. © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

PubMed Central

Al-Tonbary, Youssef; Al-Haggar, Mohammad; EL-Ashry, Rasha; EL-Dakroory, Sahar; Azzam, Hanan; Fouda, Ashraf

2009-01-01

Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment. PMID:19960046

Opioid adjuvant strategy: improving opioid effectiveness.

PubMed

Bihel, Frédéric

2016-01-01

Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

Current therapy and drug pipeline for the treatment of patients with acromegaly.

PubMed

Kumar, Sampath Satish; Ayuk, John; Murray, Robert D

2009-04-01

Acromegaly is a multisystem disease resulting from chronic exposure to supraphysiological levels of growth hormone (GH), and is associated with significant morbidity and excess mortality. The etiology is almost exclusively an underlying pituitary adenoma. Current therapeutic interventions include surgery, radiotherapy, and medical therapy. Despite surgery, around 50% of patients fail to achieve the biochemical targets shown to correlate with normalization of mortality rates. Radiotherapy is efficacious in controlling tumor growth and GH secretion; still, achievement of biochemical targets may take up to a decade and a number of safety issues have been raised with this treatment modality. Medical therapy, therefore, has an important role as adjuvant therapy in patients who fail to achieve control with surgery, or while awaiting the effects of radiotherapy to be realized. Furthermore, medical therapy is increasingly being used as primary therapy. Current medical therapies include dopaminergic agonists, somatostatin analogs, and GH receptor (GHR) antagonists. Dopaminergic agonists achieve biochemical targets in up to 30% of patients, and somatostatin analogs in around 60%. The currently available GHR antagonist pegvisomant effectively controls insulin-like growth factor-I levels in over 90% of patients; however, it has no effect on the tumor itself and has considerable financial implications. Research into optimizing the somatostatin and dopaminergic systems has led to promising advances in agonist development. Moieties with selectivity for various combinations of somatostatin receptor subtype receptors have been examined, along with molecules that additionally show high affinity for the dopaminergic D2 receptor. Of the molecules studied in vitro, only pasireotide (SOM230) and BIM-23A760 are currently undergoing further development. Other innovations to improve convenience of currently available drugs are also being investigated. Significant advances in under standing

Role of Medicinal Plants for Liver-Qi Regulation Adjuvant Therapy in Post-stroke Depression: A Systematic Review of Literature.

PubMed

Zeng, Ling-Feng; Cao, Ye; Wang, Lu; Dai, Yun-Kai; Hu, Ling; Wang, Qi; Zhu, Li-Ting; Bao, Wen-Hu; Zou, Yuan-Ping; Chen, Yun-Bo; Xu, Wei-Hua; Liang, Wei-Xiong; Wang, Ning-Sheng

2017-01-01

Current evidence demonstrated certain beneficial effects of medicinal herbs as an adjuvant therapy for post-stroke depression (PSD) in China; Chai-hu (Chinese Thorowax Root, Radix Bupleuri) is an example of a medicinal plant for Liver-Qi regulation (MPLR) in the treatment of PSD. Despite several narrative reports on the antidepressant properties of MPLR, it appears that there are no systematic reviews to summarize its outcome effects. Therefore, the aim of this review was to assess the effectiveness and safety of MPLR adjuvant therapy in patients with PSD. Seven databases were extensively searched from January 2000 until July 2016. Randomized control trials (RCTs) involving patients with PSD that compared treatment with and without MPLR were taken into account. The pooled effect estimates were calculated based on Cochrane Collaboration's software RevMan 5.3. Finally, 42 eligible studies with 3612 participants were included. Overall, MPLR adjuvant therapy showed a significantly higher effective rate (RR = 1.23; 95% CI = 1.19, 1.27; p < 0.00001) compared to those without. Moreover, the administration of MPLR was superior to abstainers regarding Hamilton Depression Scale (HAMD) score changes after 3 weeks (WMD = -4.83; 95% CI = -6.82, -2.83; p < 0.00001), 4 weeks (WMD = -3.25; 95% CI = -4.10, -2.40; p < 0.00001), 6 weeks (WMD = -4.04; 95% CI = -5.24, -2.84; p < 0.00001), 8 weeks (WMD = -4.72; 95% CI = -5.57, -3.87; p < 0.00001), and 12 weeks (WMD = -3.07; 95% CI = -4.05, -2.09; p < 0.00001). In addition, there were additive benefits in terms of response changes for the National Institutes of Health Stroke Scale (NIHSS) and other self-rating scores. No frequently occurring or serious adverse events were reported. We concluded that there is supporting evidence that adjuvant therapy with MPLR is effective in reducing the depressive symptoms and enhancing quality of life for patients with

Music as an adjuvant therapy in control of pain and symptoms in hospitalized adults: a systematic review.

PubMed

Cole, Linda C; LoBiondo-Wood, Geri

2014-03-01

The objective of this review is to evaluate the evidence regarding the use of music as an adjuvant therapy for pain control in hospitalized adults. The search terms music, music therapy, pain, adults, inpatient, and hospitalized were used to search the Cochrane Library, Cinahl, Medline, Natural Standard, and Scopus databases from January 2005 to March 2011. (A systematic review conducted by the Cochrane Collaboration has extensively covered the time frame from 1966 to 2004.) Seventeen randomized controlled trials met criteria for review and inclusion. Seven of the research studies were conducted with surgical patients, three with medical patients, one with medical-surgical patients, four with intensive care patients, and two with pregnant patients. The combined findings of these studies provide support for the use of music as an adjuvant approach to pain control in hospitalized adults. The use of music is safe, inexpensive, and an independent nursing function that can be easily incorporated into the routine care of patients. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

[Practical neoadjuvant and adjuvant therapies for rectal cancer. How many patients are actually recruited in multimodality therapy concepts? An analysis of the Tumour Centre Schwerin].

PubMed

Sauer, J; Sobolewski, K; Dommisch, K

2009-09-01

For rectal cancer in UICC stage II or III, a neoadjuvant chemoradiotherapy or short-course radiotherapy is established to reduce the incidence of local relapses. It has been documented that the neoadjuvant therapy is superior to the adjuvant therapy. In spite of the formulation of therapeutic principles in guidelines, they are not consistently applied. The actual rate of application and the reasons for a change from the recommended treatment strategy have been investigated. The data of the tumour centre West Mecklenburg were analysed. Data concerning the type and stage of rectal cancer, multimodal treatment (surgery with or without neoadjuvant therapy or adjuvant therapy) and treatment according to the level of medical care of hospitals were recorded from 2000 to 2008. In addition, in our clinic prospectively collected data of patients with rectal cancer (September 2006 until December 2008) were used to find out the reasons for the denial of neoadjuvant therapy. During the observation period we detected 348 patients with rectal cancer in UICC stage II or III in the area of the tumour centre West Mecklenburg. 16 % of these patients were treated pre-operatively. An increase in the preoperative multimodal treatment from 3 % to 39 % was observed. Hospitals with higher provisions of medical care applied the multimodal treatment 4-fold more frequently during this period of time. 55 patients of our own clinic were found to be of UICC stage II or III. 6 patients were emergency cases. The carcinoma was found in the lower or middle third of the rectum in 38 of our patients. The endosonographical examination could not adequately show the tumour or was falsely negative in 16 of these patients. A neoadjuvant treatment was started for 58 % of the patients. Overall, 76 of patients with rectal carcinoma were treated adjuvant or neoadjuvant, 62 of them with a complete treatment scheme. The application of neoadjuvant treatment for rectal carcinoma in UICC stage II or III in West

[The clinical efficacy of allergen-specific immunotherapy with water-salt extracts and adjuvant allergens for atopic asthma with household sensitization].

PubMed

Ushakova, D V; Nikonov, E L

To evaluate the clinical and economic efficiency of allergen-specific immunotherapy (ASIT); to comparatively analyze the efficiency of various therapy regimens for atopic asthma. The clinical and economic efficiency of asthma therapy using ASIT with water-salt allergen extracts or the adjuvant drug alustal 'mite allergen' and only with medicines were comparatively analyzed. The investigation enrolled 156 patients with mild and moderate atopic asthma, household allergy. In Group 1 (n = 57), ASIT was performed using the classical scheme by subcutaneous injection of house dust mite allergen (JSC 'I.I. Mechnikov Biomed', Russia). In Group 2 (n = 43), ASIT was conducted using the alustal 'mite allergen' (Stallergenes, France). Group 3 (n = 56) received only medical therapy. ASIT with both water-salt allergen extracts and the adjuvant allergen alustal is an effective treatment for mild and moderate atopic asthma. ASIT greatly reduces the need for anti-inflammatory treatment and the use of symptomatic drugs and improves the physical and psychoemotional indicators of quality of life in patients. The economic benefit of ASIT is delayed, but its use significantly reduces financing costs. ASIT is a reasonable, highly effective and ultimately cost-effective treatment in patients with atopic asthma. A variety of drugs for ASIT can choose schemes that are convenient and acceptable for each patient, which allows wider use of this treatment.

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

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

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

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

Antiretroviral therapy: current drugs.

PubMed

Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

Rational design of small molecules as vaccine adjuvants.

PubMed

Wu, Tom Y-H; Singh, Manmohan; Miller, Andrew T; De Gregorio, Ennio; Doro, Francesco; D'Oro, Ugo; Skibinski, David A G; Mbow, M Lamine; Bufali, Simone; Herman, Ann E; Cortez, Alex; Li, Yongkai; Nayak, Bishnu P; Tritto, Elaine; Filippi, Christophe M; Otten, Gillis R; Brito, Luis A; Monaci, Elisabetta; Li, Chun; Aprea, Susanna; Valentini, Sara; Calabrό, Samuele; Laera, Donatello; Brunelli, Brunella; Caproni, Elena; Malyala, Padma; Panchal, Rekha G; Warren, Travis K; Bavari, Sina; O'Hagan, Derek T; Cooke, Michael P; Valiante, Nicholas M

2014-11-19

Adjuvants increase vaccine potency largely by activating innate immunity and promoting inflammation. Limiting the side effects of this inflammation is a major hurdle for adjuvant use in vaccines for humans. It has been difficult to improve on adjuvant safety because of a poor understanding of adjuvant mechanism and the empirical nature of adjuvant discovery and development historically. We describe new principles for the rational optimization of small-molecule immune potentiators (SMIPs) targeting Toll-like receptor 7 as adjuvants with a predicted increase in their therapeutic indices. Unlike traditional drugs, SMIP-based adjuvants need to have limited bioavailability and remain localized for optimal efficacy. These features also lead to temporally and spatially restricted inflammation that should decrease side effects. Through medicinal and formulation chemistry and extensive immunopharmacology, we show that in vivo potency can be increased with little to no systemic exposure, localized innate immune activation and short in vivo residence times of SMIP-based adjuvants. This work provides a systematic and generalizable approach to engineering small molecules for use as vaccine adjuvants. Copyright © 2014, American Association for the Advancement of Science.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early Stage HER2-Positive Breast Cancer.

PubMed

Singh, Harpreet; Walker, Amanda J; Amiri-Kordestani, Laleh; Cheng, Joyce; Tang, Shenghui; Balcazar, Pamela; Barnett-Ringgold, Kimberly; Palmby, Todd R; Cao, Xianhua; Zheng, Nan; Liu, Qi; Yu, Jingyu; Pierce, William F; Daniels, Selena R; Sridhara, Rajeshwari; Ibrahim, Amna; Kluetz, Paul G; Blumenthal, Gideon M; Beaver, Julia A; Pazdur, Richard

2018-03-09

On July 17, 2017, the Food and Drug Administration (FDA) approved neratinib (NERLYNX, Puma Biotechnology, Inc) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to neratinib (n=1420) or placebo (n=1420) for one year. The primary endpoint was invasive disease-free survival (iDFS) defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distance recurrence, or death from any cause, with two years and 28 days of follow up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified hazard ratio of 0.66 (95% CI: 0.49, 0.90, p=0.008). Estimated iDFS rate at 2-years was 94.2% (95% CI: 92.6%, 95.4%) in patients treated with neratinib vs. 91.9% (95% CI: 90.2%, 93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE) with a 40% incidence of Grade 3 or 4 diarrhea and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Copyright ©2018, American Association for Cancer Research.

Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

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

Atallah, Vincent; Honore, Charles; Orbach, Daniel

Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), andmore » overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal

Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging

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

Soper, J.T.; Berchuck, A.; Clarke-Pearson, D.L.

1991-08-15

Forty-nine women with apparent Stage 1 and 2 ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as themore » first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.« less

Drug therapy in headache.

PubMed

Weatherall, Mark W

2015-06-01

All physicians will encounter patients with headaches. Primary headache disorders are common, and often disabling. This paper reviews the principles of drug therapy in headache in adults, focusing on the three commonest disorders presenting in both primary and secondary care: tension-type headache, migraine and cluster headache. The clinical evidence on the basis of which choices can be made between the currently available drug therapies for acute and preventive treatment of these disorders is presented, and information given on the options available for the emergency parenteral treatment of refractory migraine attacks and cluster headache. © Royal College of Physicians 2015. All rights reserved.

Adjuvant Anti-Angiogenesis Drugs Are No Benefit in Kidney Cancer

Cancer.gov

Results from a recent clinical trial show that post-surgical therapy with two anti-angiogenesis drugs does not improve progression-free survival for patients with kidney cancer and may cause serious side effects.

Liposomal adjuvants for human vaccines.

PubMed

Alving, Carl R; Beck, Zoltan; Matyas, Gary R; Rao, Mangala

2016-06-01

Liposomes are well-known as drug carriers, and are now critical components of two of six types of adjuvants present in licensed vaccines. The liposomal vaccine adjuvant field has long been dynamic and innovative, and research in this area is further examined as new commercial products appear in parallel with new vaccines. In an arena where successful products exist the potential for new types of vaccines with liposomal adjuvants, and alternative liposomal adjuvants that could emerge for new types of vaccines, are discussed. Major areas include: virosomes, constructed from phospholipids and proteins from influenza virus particles; liposomes containing natural and synthetic neutral or anionic phospholipids, cholesterol, natural or synthetic monophosphoryl lipid A, and QS21 saponin; non-phospholipid cationic liposomes; and combinations and mixtures of liposomes and immunostimulating ingredients as adjuvants for experimental vaccines. Liposomes containing monophosphoryl lipid A and QS21 have considerable momentum that will result soon in emergence of prophylactic vaccines to malaria and shingles, and possible novel cancer vaccines. The licensed virosome vaccines to influenza and hepatitis A will be replaced with virosome vaccines to other infectious diseases. Alternative liposomal formulations are likely to emerge for difficult diseases such as tuberculosis or HIV-1 infection.

Addition of adjuvant progesterone to physical-exam-indicated cervical cerclage to prevent preterm birth.

PubMed

Jung, Eun Young; Oh, Kyung Joon; Hong, Joon-Seok; Han, Bo Ryoung; Joo, Jung Kyung

2016-12-01

The aim of this study was to assess the effect of vaginal progesterone as an adjuvant therapy to physical-exam-indicated cervical cerclage (PEICC). This retrospective cohort study included 53 consecutive singleton women who underwent PEICC because of acute cervical insufficiency at 17-24 gestational weeks. The study population was divided into two groups: the adjuvant progesterone group (n = 18) and the non-adjuvant group (n = 35). A 200-mg dose of vaginal micronized natural progesterone was administered after cerclage in the adjuvant progesterone group. Primary outcome measure was spontaneous preterm birth (SPTB) at <36 weeks. The SPTB rate at <36 weeks in the adjuvant group was significantly lower than in the non-adjuvant group (17% vs 51%, P < 0.05). Adjuvant progesterone therapy was significantly associated with a reduction in SPTB at <36 weeks (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.69, P < 0.05) even after adjusting for known covariates, including a visible membrane size of ≥4 cm, gestational age, prior SPTB, and use of amnioreduction. The frequency of SPTB at <32 weeks, birthweight < 2500 g, and neonatal intensive care unit admission was significantly lower in the adjuvant progesterone group than in the non-adjuvant group (P < 0.05 for all). Adjuvant vaginal progesterone therapy with PEICC was associated with reductions in SPTB, low birthweight, and neonatal intensive care unit admission. © 2016 Japan Society of Obstetrics and Gynecology.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

NASA Astrophysics Data System (ADS)

Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

2016-10-01

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial.

PubMed

Pinsornsak, Piya; Niempoog, Sunyarn

2012-01-01

Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use medication for treatment of knee osteoarthritis which has the analgesic and anti-inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that has the anti-inflammatory effect by down regulate activation of NF-kappaB and proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1, Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the combination therapy which can increase safety and efficacy with less side effect compare with monotherapy regimen especially when the medicine has the different mechanism of action. The present study is the double blind prospective randomized control trial to evaluate the efficacy of curcumin as an adjuvant therapy of diclofenac in primary knee osteoarthritis. 44 patients were randomized to take NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) every month for 3 months. At the end of study 36 patients were completed for the first group and 37 for the study group. There was no difference in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories symptom, pain, function in daily living, function in sport and recreation and knee related quality of life. The curcumin with diclofenac group had tendency to be better in Pain and Function in daily living, but there were no statistic different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056), p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F = 0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the potential beneficial

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations

PubMed Central

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu

2016-01-01

Background Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non‐small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR‐tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR‐mutated NSCLC patients undergoing resection of stage IB–IIIA. Methods Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. Results The median follow‐up time was 30 months (range 24–41). At the data cut‐off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two‐year disease‐free survival (DFS) rate was 85%. No recurrence occurred in the high‐risk stage IB subgroup during the follow‐up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS (P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin‐related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Conclusions Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. PMID:27766784

Adjuvant bisphosphonate treatment for breast cancer: why did something so elegant become so complicated?

PubMed

Clemons, Mark; Russell, Kent; Costa, Luis; Addison, Christina L

2012-07-01

Bisphosphonate therapy has revolutionized the care of patients with metastatic bone disease. With its demonstrated activity and anti-tumour effects in preclinical studies it was natural to transition these agents to testing in the adjuvant setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest or no benefit or even harm. We sought to explore whether there were specific patient cohorts or treatment strategies that were most likely to benefit from adjuvant bisphosphonate therapy. We compared trial designs, patient characteristics and outcomes from the six published and two presented randomized adjuvant bisphosphonate trials. Differences in trial design and patient populations make direct comparisons complicated. The most efficacious use of adjuvant bisphosphonates appears to be in patients with either biopsy evidence of osseous micrometastases, were post-menopausal or had estrogen receptor-positive tumours. Despite tremendous optimism regarding adjuvant bisphosphonate therapy, results from large trials are conflicting. Further investigation into factors influencing response to bisphosphonate treatment or selection of appropriate sub-groups of patients with desirable response characteristics is warranted.

The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

PubMed

Eggermont, Alexander M M; Dummer, Reinhard

2017-11-01

The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

Timing of Radiotherapy and Outcome in Patients Receiving Adjuvant Endocrine Therapy

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

Karlsson, Per, E-mail: per.karlsson@oncology.gu.s; Cole, Bernard F.; International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA

2011-06-01

Purpose: To evaluate the association between the interval from breast-conserving surgery (BCS) to radiotherapy (RT) and the clinical outcome among patients treated with adjuvant endocrine therapy. Patients and Methods: Patient information was obtained from three International Breast Cancer Study Group trials. The analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. The patients were divided into two groups according to the median number of days between BCS and RT and into four groups according to the quartile of time between BCS and RT. The endpoints were the interval to local recurrence, disease-free survival, and overall survival.more » Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results: The median interval between BCS and RT was 77 days. RT timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors, no significant effect of a RT delay {<=}20 weeks was found. The adjusted hazard ratio for RT within 77 days vs. after 77 days was 0.94 (95% confidence interval [CI], 0.47-1.87) for the interval to local recurrence, 1.05 (95% CI, 0.82-1.34) for disease-free survival, and 1.07 (95% CI, 0.77-1.49) for overall survival. For the interval to local recurrence the adjusted hazard ratio for {<=}48, 49-77, and 78-112 days was 0.90 (95% CI, 0.34-2.37), 0.86 (95% CI, 0.33-2.25), and 0.89 (95% CI, 0.33-2.41), respectively, relative to {>=}113 days. Conclusion: A RT delay of {<=}20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, the timing of RT was not significantly associated with the interval to local recurrence, disease-free survival, or overall survival.« less

Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients.

PubMed

Crew, Katherine D; Capodice, Jillian L; Greenlee, Heather; Apollo, Arlyn; Jacobson, Judith S; Raptis, George; Blozie, Kimberly; Sierra, Alex; Hershman, Dawn L

2007-12-01

Aromatase inhibitors (AIs) have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. However, patients receiving AIs may experience joint symptoms, which may lead to early discontinuation of this effective therapy. We hypothesize that acupuncture is a safe and effective treatment for AI-induced arthralgias. Postmenopausal women with early-stage breast cancer who had self-reported musculoskeletal pain related to adjuvant AI therapy were randomized in a crossover study to receive acupuncture twice weekly for 6 weeks followed by observation or vice-versa. The intervention included full body and auricular acupuncture, and a joint-specific point prescription. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life measure, and serum levels of inflammatory markers, IL-1 beta and TNF-alpha. Twenty-one women were enrolled and two discontinued early. From baseline to the end of treatment, patients reported improvement in the mean BPI-SF worst pain scores (5.3 to 3.3, p = 0.01), pain severity (3.7 to 2.5, p = 0.02), and pain-related functional interference (3.1 to 1.7, p = 0.02), as well as the WOMAC function subscale and FACT-G physical well-being (p = 0.02 and 0.04, respectively). No adverse events were reported. In this pilot study, acupuncture reduced AI-related joint symptoms and improved functional ability and was well-tolerated. Musculoskeletal side effects are common among breast cancer survivors on adjuvant AI therapy, therefore, effective treatments are needed for symptom relief and to improve adherence to these life-saving medications.

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

PubMed

Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

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

Drug self-delivery systems for cancer therapy.

PubMed

Qin, Si-Yong; Zhang, Ai-Qing; Cheng, Si-Xue; Rong, Lei; Zhang, Xian-Zheng

2017-01-01

Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

21 CFR 182.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 182.99 Section 182.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182...

21 CFR 182.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 182.99 Section 182.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182...

21 CFR 182.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 182.99 Section 182.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182...

21 CFR 182.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide chemicals. 182.99 Section 182.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182...

[Application of half-dose depot long-acting triptorelin in postoperative adjuvant therapy for endometriosis].

PubMed

Liu, Xia; Zhang, Hong-xia; Wang, Li-ping; Fu, Wei-ping

2013-01-15

To evaluate the efficacy and adverse effects of half-dose depot long-acting triptorelin in the therapy of endometriosis. The efficacy and adverse effects of routine-dose or half-dose triptorelin in postoperative endometriosis patients were prospectively observed. A total of 186 postoperative patients with moderate or severe endometriosis received an intramuscular injection of triptorelin every 28 days for 6 times. They were randomly divided into 3 groups, i.e. half-dose group (n = 99): 1.875 mg each time; "draw-back" group (n = 52): 3.75 mg first time, then 1.875 mg each time; and routine-dose group (n = 35): 3.75 mg each time. Amenorrhea was effectively induced in all patients after the second injection. There was no significant difference in the rate of serum E2 level at Day 28 of every injection below the upper limit of "estrogen threshold (110 - 146 pmol/L)" not stimulating ectopic endometrium proliferation among half-dose group, "draw-back" group and routine-dose group (99% vs 100% and 99.0%, P > 0.05), the percentage of E2 < 37 pmol/L in E2 < 110 pmol/L in half-dose group was significantly lower than that in "draw-back" and routine-dose groups after 2-5(th) injection (69% vs 79% and 85%, P < 0.01), but there was no significant difference after first half-dose and routine-dose injection (71% vs 73%, P > 0.05). No significant difference existed in the rate of pelvic pain relief during the first returning menstruation and the recurrence rate of endometriosis within 1 year postoperation among three groups (both P > 0.05). However, the incidences of menopausal syndrome and severe menopausal syndrome in half-dose group were significantly lower than those in "draw-back" and routine-dose groups (both P < 0.01). And the incompletion rate of six-time drug for severe menopause syndrome was also significantly lower (P < 0.05) while the completion rate of six-time drug use in half-dose group was significantly higher (P < 0.05). As a postoperative adjuvant, half-dose depot

Artificial intelligence in drug combination therapy.

PubMed

Tsigelny, Igor F

2018-02-09

Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Health promotion for young patients with haemophilia. Counselling, adjuvant exercise therapy and school sports.

PubMed

Sondermann, Judith; Herbsleb, Marco; Stanek, Frank-Detlef; Gabriel, Holger; Kentouche, Karim

2017-05-10

The haemophilia treatment centre of the Clinic for Children and Youth Medicine in Jena extends medical care by health-promotion measures, namely: health counselling, adjuvant exercise therapy and school sports. In addition to the regular medical checks at the treatment centre patients are examined regarding physical fitness, joint situation, quality of life in general and disease-specific manner, as well as psycho-social and nutritional behaviour. Findings and medical results of the examinations are integrated into an individual advice on therapy, school sports, and health recommendations. This aimed at strengthening health-related resources and minimizing potential injuries. First long-term evaluation shows an increase of activity behaviour and physical fitness without increasing bleeding rate and maintained joint function. Combining functional prevention diagnostics and individual health counselling shows signs of improved patient's health knowledge, self-competence and physical fitness.

Low-intensity ultrasound adjuvant therapy: enhancement of doxorubicin-induced cytotoxicity and the acoustic mechanisms involved.

PubMed

Kondo, Takashi; Yoshida, Toru; Ogawa, Ryohei; Hassan, Mariame A; Furusawa, Yukihiro; Zhao, Qing-Li; Watanabe, Akihiko; Morii, Akihiro; Feril, Loreto B; Tachibana, Katsuro; Kitagawa, Hiroshi; Tabuchi, Yoshiaki; Takasaki, Ichiro; Shehata, Mohammad H; Kudo, Nobuki; Tsukada, Kazuhiro

2009-06-01

In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions.

Adjuvant therapy for gastric cancer: what have we learned since INT0116?

PubMed

Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

2015-04-07

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

Drug-therapy networks and the prediction of novel drug targets

PubMed Central

Spiro, Zoltan; Kovacs, Istvan A; Csermely, Peter

2008-01-01

A recent study in BMC Pharmacology presents a network of drugs and the therapies in which they are used. Network approaches open new ways of predicting novel drug targets and overcoming the cellular robustness that can prevent drugs from working. PMID:18710588

Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

PubMed

Rule, William G; Allred, Jacob B; Pockaj, Barbara A; Markovic, Svetomir N; DiCaudo, David J; Erickson, Lori A; Deming, Richard L; Schild, Steven E

2016-08-01

To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy.

PubMed

Sato, Junya; Kashiwaba, Masahiro; Komatsu, Hideaki; Ishida, Kazushige; Nihei, Satoru; Kudo, Kenzo

2016-05-01

Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness. This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations.

PubMed

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu; Zhang, Yi

2016-09-01

Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. The median follow-up time was 30 months (range 24-41). At the data cut-off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two-year disease-free survival (DFS) rate was 85%. No recurrence occurred in the high-risk stage IB subgroup during the follow-up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS ( P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin-related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Potential drug therapies for the treatment of fibromyalgia.

PubMed

Lawson, Kim

2016-09-01

Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.

Drug therapy smartens up

NASA Astrophysics Data System (ADS)

Martin, Christian

2015-11-01

The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

PubMed

McGunigal, Mary; Pollock, Ariel; Doucette, John T; Liu, Jerry; Chadha, Manjeet; Kalir, Tamara; Gupta, Vishal

2018-06-01

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012

Open-loop-feedback control of serum drug concentrations: pharmacokinetic approaches to drug therapy.

PubMed

Jelliffe, R W

1983-01-01

Recent developments to optimize open-loop-feedback control of drug dosage regimens, generally applicable to pharmacokinetically oriented therapy with many drugs, involve computation of patient-individualized strategies for obtaining desired serum drug concentrations. Analyses of past therapy are performed by least squares, extended least squares, and maximum a posteriori probability Bayesian methods of fitting pharmacokinetic models to serum level data. Future possibilities for truly optimal open-loop-feedback therapy with full Bayesian methods, and conceivably for optimal closed-loop therapy in such data-poor clinical situations, are also discussed. Implementation of these various therapeutic strategies, using automated, locally controlled infusion devices, has also been achieved in prototype form.

Antibiotic Adjuvants: Rescuing Antibiotics from Resistance.

PubMed

Wright, Gerard D

2016-11-01

Rooted in the mechanism of action of antibiotics and subject to bacterial evolution, antibiotic resistance is difficult and perhaps impossible to overcome. Nevertheless, strategies can be used to minimize the emergence and impact of resistance. Antibiotic adjuvants offer one such approach. These are compounds that have little or no antibiotic activity themselves but act to block resistance or otherwise enhance antibiotic action. Antibiotic adjuvants are therefore delivered in combination with antibiotics and can be divided into two groups: Class I agents that act on the pathogen, and Class II agents that act on the host. Adjuvants offer a means to both suppress the emergence of resistance and rescue the activity of existing drugs, offering an orthogonal strategy complimentary to new antibiotic discovery VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential drug interactions in patients given antiretroviral therapy

PubMed Central

dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-01-01

ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. PMID:27878224

American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer

PubMed Central

Burstein, Harold J.; Prestrud, Ann Alexis; Seidenfeld, Jerome; Anderson, Holly; Buchholz, Thomas A.; Davidson, Nancy E.; Gelmon, Karen E.; Giordano, Sharon H.; Hudis, Clifford A.; Malin, Jennifer; Mamounas, Eleftherios P.; Rowden, Diana; Solky, Alexander J.; Sowers, MaryFran R.; Stearns, Vered; Winer, Eric P.; Somerfield, Mark R.; Griggs, Jennifer J.

2010-01-01

Purpose To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor–positive breast cancer. Methods A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. Results An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. Conclusion The Update Committee recommends that postmenopausal women with hormone receptor–positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy. PMID:20625130

21 CFR 172.710 - Adjuvants for pesticide use dilutions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Adjuvants for pesticide use dilutions. 172.710 Section 172.710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Other Specific Usage...

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.

In vitro activity of nicotinamide/antileishmanial drug combinations.

PubMed

Gazanion, Elodie; Vergnes, Baptiste; Seveno, Marie; Garcia, Deborah; Oury, Bruno; Ait-Oudhia, Khatima; Ouaissi, Ali; Sereno, Denis

2011-01-01

To improve the management of leishmaniasis, new drugs and/or alternative therapeutic strategies are required. Combination therapy of antileishmanial drugs is currently considered as one of the most rational approaches to lower treatment failure rate and limit drug resistance spreading. Nicotinamide (NAm), also known as vitamin B3 that is already is used in human therapy, exerts in vitro antileishmanial activity. Drug combination studies, performed on L. infantum axenic amastigotes, revealed that NAm significantly improves the antileishmanial activity of trivalent antimony in a synergistic manner while it shows additive activity with amphotericin B and slightly antagonizes pentamidine activity. NAm also significantly increases the toxicity of pentavalent antimony against the intracellular forms of L. infantum, L. amazonensis and L. braziliensis. The potential of NAm to be used as adjuvant during leishmaniasis chemotherapy is further discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Adjuvant Treatment for Older Women with Invasive Breast Cancer

PubMed Central

Jolly, Trevor A; Williams, Grant R; Bushan, Sita; Pergolotti, Mackenzi; Nyrop, Kirsten A; Jones, Ellen L; Muss, Hyman B

2016-01-01

Older women experience a large share of breast cancer incidence and death. With the projected rise in the number of older cancer patients, adjuvant chemo-, radiation and endocrine therapy management will become a key component of breast cancer treatment in older women. Many factors influence adjuvant treatment decisions including patient preferences, life expectancy and tumor biology. Geriatric assessment predicts important outcomes, identifies key deficits, and can aid in the decision making process. This review utilizes clinical vignettes to illustrate core principles in adjuvant management of breast cancer in older women and suggests an approach incorporating life expectancy and geriatric assessment. PMID:26767315

Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

PubMed

Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

2014-03-15

Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors. © 2013 UICC.

Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma

PubMed Central

Tsen, Andrew R.; Long, Patrick M.; Driscoll, Heather E.; Davies, Matthew T.; Teasdale, Benjamin A.; Penar, Paul L.; Pendlebury, William W.; Spees, Jeffrey L.; Lawler, Sean E.; Viapiano, Mariano S.; Jaworski, Diane M.

2013-01-01

Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic, and hypoacetylated mesenchymal glioma tumors. PMID:23996800

Adjuvant strategies for potentiation of antibiotics to overcome antimicrobial resistance.

PubMed

Pieren, Michel; Tigges, Marcel

2012-10-01

Alarming facts about the occurrence and spreading of multiple antibiotic resistant bacteria have caught the attention of global surveillance authorities and public media. The demand for novel effective antimicrobial drugs is high and on the rise while, at the same time, the supply of fresh 'magic bullets' is drying up. This review summarizes examples of recent strategies for development of adjunctive antibiotic therapies that overcome microbial resistance and thus rejuvenate the existing arsenal of drugs. Recent studies have demonstrated the potential of compounds that inhibit the action of the repressor protein implicated in ethionamide resistance, thus stimulating activation of the drug and thereby restoring the activity of the antibiotic for treatment of Mycobacterium tuberculosis. Such specific interference with regulators or signal transduction mechanisms involved in antibiotic resistance or virulence provides a new toolbox for novel combinations of antimicrobial drugs with adjuvant molecules lacking intrinsic antibiotic activity. In addition to the development of new antibiotics and vaccination initiatives this strategy of restoring or potentiating the activity of existing antibiotics may help to postpone the day when antibiotics are no longer generally efficacious. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

PubMed Central

Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

2014-01-01

Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

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.

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.

Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy

PubMed Central

Derzko, C.; Elliott, S.; Lam, W.

2007-01-01

Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements—all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement—most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)—may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be

Recent advances in drug therapy for epilepsy.

PubMed Central

Bruni, J.

1979-01-01

Recent advances in drug therapy for epilepsy have contributed to the reduction in the proportion of persons whose epilepsy is uncontrolled. New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses. Carbamazepine has recently been introduced for the treatment of generalized tonic-clonic and partial seizures. Clonazepam has been found of particular benefit in the treatment of absence and myoclonic seizures. Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures. Monitoring of the plasma concentration of antiepileptic drugs has added greatly to the achievement of optimal drug therapy and the prevention of toxic effects. PMID:371777

Design and Synthesis of Potent Quillaja Saponin Vaccine Adjuvants

PubMed Central

Adams, Michelle M.; Damani, Payal; Perl, Nicholas R.; Won, Annie; Hong, Feng

2010-01-01

The success of antitumor and antiviral vaccines often requires the use of an adjuvant, a substance that significantly enhances the immune response to a co-administered antigen. Only a handful of adjuvants have both sufficient potency and acceptable toxicity for clinical investigation. One promising adjuvant is QS-21, a saponin natural product that is the immunopotentiator of choice in many cancer and infectious disease vaccine clinical trials. However, the therapeutic promise of QS-21 adjuvant is curtailed by several factors, including its scarcity, difficulty in purification to homogeneity, dose-limiting toxicity, and chemical instability. Here we report the design, synthesis, and evaluation of chemically stable synthetic saponins. These novel, amide-modified, non-natural substances exhibit immunopotentiating effects in vivo that rival or exceed that of QS-21 in evaluations with the GD3-KLH melanoma conjugate vaccine. The highly convergent synthetic preparation of these novel saponins establishes new avenues for discovering improved molecular adjuvants for specifically tailored vaccine therapies. PMID:20088518

Adjuvant chemotherapy for breast cancer patients: patients' expectations and physicians' attitudes.

PubMed

Barak, Frida; Ostrowsky, Lev A; Kreitler, Shulamith

2012-06-01

Findings show that there is a certain degree of refusal on the part of breast cancer patients to undergo adjuvant therapy. Accordingly, the major goals of the study were, first, to learn more about the beliefs of breast cancer patients in regard to adjuvant therapy; second, to find out about the sources of the patients' beliefs; and third, to learn about the attitudes of oncologists concerning the same aspects of adjuvant therapy to which the patients' beliefs referred. The participants were 92 breast cancer patients (mean age 61.2) and 57 doctors of both genders specialized in oncology or affiliated domains. Both groups were administered questionnaires referring to goals of adjuvant treatment, the chances of attaining these goals, side effects, and difficulty of the treatment. Doctors were specifically asked about the views they thought proper to communicate to patients in regard to the mentioned issues. Patients were also asked about whether they had doubts about the treatment and sources of information. The findings showed disparities between the views of patients and doctors in regard to goals, chances of attainment, side effects, and difficulty of treatment. Patients endorsed more goals than doctors and tended to assign to them lower chances of attainment. Doctors were divided in their views about whether to communicate the side effects and difficulties. The results reveal the importance of outlining goals for patients undergoing adjuvant treatment and the disagreements between doctors about what should be communicated to patients, and highlight the complexity of providing to patients information that is both scientifically correct and emotionally helpful.

Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

PubMed

Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

2010-01-01

With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

Speech-language therapy program for mouth opening in patients with oral and oropharyngeal cancer undergoing adjuvant radiotherapy: a pilot study.

PubMed

Marrafon, Caroline Somera; Matos, Leandro Luongo; Simões-Zenari, Marcia; Cernea, Claudio Roberto; Nemr, Katia

2018-01-01

Purpose Assess the effectiveness of an orofacial myofunctional therapeutic program in patients with oral or oropharyngeal cancer submitted to adjuvant radiotherapy through pre- and post-program comparison of maximum mandibular opening. Methods Prospective study involving five adult patients and five elderly patients postoperatively to oral cavity/oropharynx surgery who were awaiting the beginning of radiotherapy or had undergone fewer than five treatment sessions. The study participants had their maximum jaw opening measured using a sliding caliper at the beginning and end of the program. Two mobility exercises and three mandibular traction exercises were selected and weekly monitored presentially for 10 weeks. Descriptive data and pre- and post-therapy comparative measures were statistically analyzed using the Wilcoxon test. Results Ten patients (two women and eight men) with mean age of 58.4 years, median of 57.0 years, completed the therapeutic program. They presented mean maximum mandibular opening of 31.6 ± 11.7 and 36.4 ± 8.0 mm pre- and post-therapy, respectively (p =0.021). Conclusion The proposed orofacial myofunctional therapeutic program increased the maximum jaw opening of patients referred to adjuvant radiotherapy for oral cavity or oropharynx cancer treatment.

Dose density in adjuvant chemotherapy for breast cancer.

PubMed

Citron, Marc L

2004-01-01

Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

The outweigh of toxicity versus risk of recurrence for adjuvant interferon therapy: a survey in German melanoma patients and their treating physicians.

PubMed

Kähler, Katharina C; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Hauschild, Axel; Heinzerling, Lucie; Livingstone, Elisabeth; Loquai, Carmen; Müller-Brenne, Tina; Schadendorf, Dirk; Utikal, Jochen; Wagner, Tobias; Augustin, Matthias

2018-05-25

After more than two decades with interferon alfa-2a and 2b (IFN) as the only approved drugs in the adjuvant setting for melanoma, new treatment approaches like immune checkpoint inhibitors and BRAF-MEK inhibitors improve the progression free survival (PFS) and also the overall survival (OS). We compared physicians' preferences ("utilities") for health states associated with IFN therapy to their patients' preferences. Utilities describe a preference for a specific health state on a scale of 0 (as bad as death) to 1.0 (perfect health). We assessed utilities for health states associated with adjuvant IFN using the standard gamble technique in 108 physicians and 130 melanoma patients. Four IFN toxicity scenarios and three outcome scenarios were given to the participants. Both groups were asked for the 5-year disease free survival (DFS) they would need to accept the described IFN-related side effects. In both groups, utilities for melanoma relapse were significantly lower than for IFN side effects, showing that toxicity was more acceptable than relapse. Physicians indicated higher utilities for each scenario and needed lower 5-year DFS both in case of mild-to-moderate and severe side effects. Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, while physicians only required a chance of 40% and 50%, respectively. Both physicians and patients rated melanoma recurrence much lower than even severe IFN side effects. In direct comparison, physicians rated cancer-related scenarios more positively and accepted IFN toxicity for an even lower treatment benefit.

Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: A pilot study

PubMed Central

Kahn, S. Anthony; Mullin, Christine M.; de Lorimier, Louis-Philippe; Burgess, Kristine E.; Risbon, Rebecca E.; Fred, Rogers M.; Drobatz, Kenneth; Clifford, Craig A.

2013-01-01

Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA. PMID:23997259

Acupuncture as adjuvant therapy in thalamic syndrome: case report.

PubMed

Santos, Alysson Bruno Oliveira; Gozzani, Judymara Lauzi

2011-01-01

Cerebrovascular diseases are responsible for a large proportion of deaths in the world. Among survivors, the majority of limiting sequelae observed is motor in origin; but when sensorial pathways or centers are affected patients can evolve with sensorial changes in the body region represented by the area of the brain affected. When the affected area is related to the thalamus the patient might develop thalamic syndrome. The objective of this report was to demonstrate the use of electroacupuncture as adjuvant in the treatment of central pain, diagnosed as thalamic syndrome difficult to control with pharmacologic therapy. This is a 46 year-old female with history of ischemic stroke in the left temporoparietal region in April 2003 that evolved to right hemiparesis and hemitaxia. One year later, the patient developed continuous, insidious pain on the right side of the body with allodynia and hyperalgia, diagnosed as thalamic syndrome. In January 2006, she was admitted to the department of pain therapy and palliative care of Santa Casa de Misericórdia de São Paulo where pharmacologic treatment was instituted with poor response; she was scheduled for neurofunctional surgery. In July 2009, electroacupuncture, in an attempt to obtain better pain control, was proposed to the patient. Electroacupuncture was done on points in the scalp. After the 11(th) session, her pain was controlled, with no use of opioids or topical amitriptyline, her well-being had increased, her motor coordination improved, she presented global pain reduction, complete in hand and face. The efficacy of electroacupuncture in pain control and well-being are in agreement with modern studies which demonstrated activation of antinociceptive pathways in the brain. Controlled prospective studies are required to reaffirm and consolidate electroacupuncture as an important technique in controlling central pain. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

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

Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

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

Sher, David J., E-mail: dsher@lroc.harvard.edu; Thotakura, Vijaya; Balboni, Tracy A.

2011-11-15

Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distributionmore » of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

PubMed

Finocchiaro, L M E; Glikin, G C

2008-02-01

We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

Effectiveness of high-frequency transcutaneous electrical nerve stimulation at tender points as adjuvant therapy for patients with fibromyalgia.

PubMed

Carbonario, F; Matsutani, L A; Yuan, S L K; Marques, A P

2013-04-01

Fibromyalgia is a chronic pain syndrome associated with sleep disorders, fatigue and psychological symptoms. Combinations therapies, such as electrotherapy and therapeutic exercises have been used in the clinical practice. To assess the efficacy of high-frequency transcutaneous electrical nerve stimulation (TENS) as an adjuvant therapy to aerobic and stretching exercises, for the treatment of fibromyalgia. Controlled clinical trial. Unit of rehabilitation of a public hospital. Twenty-eight women aged 52.4±7.5 years, with fibromyalgia. A visual analogue scale measured pain intensity; tender points pain threshold, by dolorimetry; and quality of life, by the Fibromyalgia Impact Questionnaire. All subjects participated in an eight-week program consisting of aerobic exercises, followed by static stretching of muscle chains. In TENS group, high-frequency (150 Hz) was applied on bilateral tender points of trapezium and supraspinatus. TENS group had a greater pain reduction (mean change score=-2.0±2.9 cm) compared to Without TENS group (-0.7±3.7 cm). There was a difference between mean change scores of each group for pain threshold (right trapezium: 0.2±1 kg/cm² in TENS group and -0.2±1.2 kg/cm² in Without TENS group). In the evaluation of clinically important changes, patients receiving TENS had relevant improvement of pain, work performance, fatigue, stiffness, anxiety and depression compared to those not receiving TENS. It has suggested that high-frequency TENS as an adjuvant therapy is effective in relieving pain, anxiety, fatigue, stiffness, and in improving ability to work of patients with fibromyalgia. High-frequency TENS may be used as a short-term complementary treatment of fibromyalgia.

Environmental adjuvants, apoptosis and the censorship over autoimmunity.

PubMed

Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

2005-11-01

Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

Underuse of Breast Cancer Adjuvant Treatment: Patient Knowledge, Beliefs, and Medical Mistrust

PubMed Central

Bickell, Nina A.; Weidmann, Jessica; Fei, Kezhen; Lin, Jenny J.; Leventhal, Howard

2009-01-01

Purpose Little is known about why women with breast cancer who have surgery do not receive proven effective postsurgical adjuvant treatments. Methods We surveyed 258 women who recently underwent surgical treatment at six New York City hospitals for early-stage breast cancer about their care, knowledge, and beliefs about breast cancer and its treatment. As per national guidelines, all women should have received adjuvant treatment. Adjuvant treatment data were obtained from inpatient and outpatient charts. Factor analysis was used to create scales scored to 100 of treatment beliefs and knowledge, medical mistrust, and physician communication about treatment. Bivariate and multivariate analyses assessed differences between treated and untreated women. Results Compared with treated women, untreated women were less likely to know that adjuvant therapies increase survival (on a 100-point scale; 66 v 75; P < .0001), had greater mistrust (64 v 53; P = .001), and had less self-efficacy (92 v 97; P < .05); physician communication about treatment did not affect patient knowledge of treatment benefits (r = 0.8; P = .21). Multivariate analysis found that untreated women were more likely to be 70 years or older (adjusted relative risk [aRR], 1.11; 95% CI, 1.00 to 1.13), to have comorbidities (aRR, 1.10; 95% CI, 1.04 to 1.12), and to express mistrust in the medical delivery system (aRR, 1.003; 95% CI, 1.00 to 1.007), even though they were more likely to believe adjuvant treatments were beneficial (aRR, 0.99; 95% CI, 0.98 to 0.99; model c, 0.84; P ≤ .0001). Conclusion Patient knowledge and beliefs about treatment and medical mistrust are mutable factors associated with underuse of effective adjuvant therapies. Physicians may improve cancer care by ensuring that discussions about adjuvant therapy include a clear presentation of the benefits, not just the risks of treatment, and by addressing patient trust in and concerns about the medical system. PMID:19770368

'Smart' nanoparticles as drug delivery systems for applications in tumor therapy.

PubMed

Fang, Zhi; Wan, Lin-Yan; Chu, Liang-Yin; Zhang, Yan-Qiong; Wu, Jiang-Feng

2015-01-01

In the therapy of clinical diseases such as cancer, it is important to deliver drugs directly to tumor sites in order to maximize local drug concentration and reduce side effects. This objective may be realized by using 'smart' nanoparticles (NPs) as drug delivery systems, because they enable dramatic conformational changes in response to specific physical/chemical stimuli from the diseased cells for targeted and controlled drug release. In this review, we first briefly summarize the characteristics of 'smart' NPs as drug delivery systems in medical therapy, and then discuss their targeting transport, transmembrane and endosomal escape behaviors. Lastly, we focus on the applications of 'smart' NPs as drug delivery systems for tumor therapy. Biodegradable 'smart' NPs have the potential to achieve maximum efficacy and drug availability at the desired sites, and reduce the harmful side effects for healthy tissues in tumor therapy. It is necessary to select appropriate NPs and modify their characteristics according to treatment strategies of tumor therapy.

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

PubMed Central

Lesiuk, Teresa

2016-01-01

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

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

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

PubMed

Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

2012-03-14

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

PubMed

Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

2010-05-01

No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (therapy (>7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5-fluorouracil after mesorectal excision with lateral pelvic lymph node dissection for stage iii lower rectal cancer.

PubMed

Iwasa, Satoru; Souda, Hiroaki; Yamazaki, Kentaro; Takahari, Daisuke; Miyamoto, Yuji; Takii, Yasumasa; Ikeda, Satoshi; Hamaguchi, Tetsuya; Kanemitsu, Yukihide; Shimada, Yasuhiro

2015-03-01

Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Adjuvant Therapy With Zoledronic Acid in Patients With Breast Cancer: A Systematic Review and Meta-Analysis

PubMed Central

Polyzos, Nikolaos P.; Coleman, Robert E.; Gnant, Michael; Eidtmann, Holger; Brufsky, Adam M.; Aft, Rebecca; Tevaarwerk, Amye J.; Swenson, Karen; Lind, Pehr; Mauri, Davide

2013-01-01

Background. The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I–III) breast cancer. Materials and Methods. We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70–0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70–1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio [OR], 0.94; 95% CI, 0.64–1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63–0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%. Conclusion. Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment. PMID:23404816

SPR741, an Antibiotic Adjuvant, Potentiates the In Vitro and In Vivo Activity of Rifampin against Clinically Relevant Extensively Drug-Resistant Acinetobacter baumannii

PubMed Central

Reinhart, Alexandria A.; Alamneh, Yonas A.; Pucci, Michael J.; Si, Yuanzheng; Abu-Taleb, Rania; Shearer, Jonathan P.; Demons, Samandra T.; Tyner, Stuart D.; Lister, Troy

2017-01-01

ABSTRACT Acinetobacter baumannii is responsible for 10% of all nosocomial infections and has >50% mortality rates when causing ventilator-associated pneumonia. In this proof-of-concept study, we evaluated SPR741, an antibiotic adjuvant that permeabilizes the Gram-negative membrane, in combination with rifampin against AB5075, an extensively drug-resistant (XDR) A. baumannii strain. In standard in vitro assays and in a murine pulmonary model, we found that this drug combination can significantly reduce bacterial burden and promote animal survival despite an aggressive infection. PMID:28947471

Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

PubMed Central

Degli Stefani, Mario; Biasutti, Michele

2016-01-01

Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

Emerging Trends in Surgical and Adjuvant Radiation Therapies among Women Diagnosed with Ductal Carcinoma in Situ

PubMed Central

Shiyanbola, Oyewale O.; Sprague, Brian L.; Hampton, John M.; Dittus, Kim; James, Ted A.; Herschorn, Sally; Gangnon, Ronald E.; Weaver, Donald L.; Trentham-Dietz, Amy

2016-01-01

BACKGROUND The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. We sought to investigate recent patterns in DCIS treatment by demographic factors. METHODS Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group and geographic region. The likelihood of receiving specific treatment modalities was analyzed using multivariable logistic regression. RESULTS DCIS cases were most frequently treated with breast conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation following BCS plateaued at around 70% after 2007, with increasing utilization of mastectomy beyond 2005. Additionally, there was an increasing trend in post-mastectomy reconstruction over time, and women of African ancestry (odds ratio, 0.69; 95% confidence interval,0.66–0.72) and Hispanic women were less likely to undergo reconstruction (odds ratio, 0.83; 95% confidence interval, 0.78–0.89) compared to women of European ancestry. A similar trend was observed in contralateral risk reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk reducing mastectomy among all ancestral/ethnic groups. CONCLUSION Recent trends demonstrate a plateau in radiation therapy administration following BCS, with increasing utilization of mastectomy, reconstruction and contralateral risk reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. PMID:27244699

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

PubMed

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Synergistic effects of plasma-activated medium and chemotherapeutic drugs in cancer treatment

NASA Astrophysics Data System (ADS)

Chen, Chao-Yu; Cheng, Yun-Chien; Cheng, Yi-Jing

2018-04-01

Chemotherapy is an important treatment method for metastatic cancer, but the drug-uptake efficiency of cancer cells needs to be enhanced in order to diminish the side effects of chemotherapeutic drugs and improve survival. The use of a nonequilibrium low-temperature atmospheric-pressure plasma jet (APPJ) has been demonstrated to exert selective effects in cancer therapy and to be able to enhance the uptake of molecules by cells, which makes an APPJ a good candidate adjuvant in combination chemotherapy. This study estimated the effects of direct helium-based APPJ (He-APPJ) exposure (DE) and He-APPJ-activated RPMI medium (PAM) on cell viability and migration. Both of these treatments decreased cell viability and inhibited cell migration, but to different degrees in different cell types. The use of PAM as a culture medium resulted in the dialkylcarbocyanine (DiI) fluorescent dye entering the cells more efficiently. PAM was combined with the anticancer drug doxorubicin (Doxo) to treat human heptocellular carcinoma HepG2 cells and human adenocarcinomic alveolar basal epithelial A549 cells. The results showed that the synergistic effects of combined PAM and Doxo treatment resulted in stronger lethality in cancer cells than did PAM or Doxo treatment alone. To sum up, PAM has potential as an adjuvant in combination with other drugs to improve curative cancer therapies.

Family Therapy for the Drug User: Conceptual and Practical Considerations

ERIC Educational Resources Information Center

Davis, Donald I.; And Others

1978-01-01

National surveys suggest that many drug treatment programs are utilizing family therapy. It is frequently the choice of treatment. Controlled studies of family therapy in drug abuse are sparce but encouraging. (MFD)

Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment

PubMed Central

Yasueda, Asuka; Urushima, Hayato; Ito, Toshinori

2015-01-01

Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy. PMID:26503419

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.

Marathon Group Therapy with Former Drug Users.

ERIC Educational Resources Information Center

Page, Richard C.; Mannion, John

1980-01-01

Discusses the effects of marathon group therapy on attitudes of former drug users in a residential drug treatment center. Experimental group members responded higher on the group counseling evaluative subscale and lower on the guilt evaluative subscale than control members. (Author)

Potential Proinvasive or Metastatic Effects of Preclinical Antiangiogenic Therapy Are Prevented by Concurrent Chemotherapy.

PubMed

Paez-Ribes, Marta; Man, Shan; Xu, Ping; Kerbel, Robert S

2015-12-15

To resolve a controversy involving the therapeutic impact of antiangiogenic drugs and particularly antibodies targeting the VEGF pathway, namely, a body of preclinical mouse therapy studies showing such drugs can promote invasion and/or distant metastasis when used as monotherapies. In contrast, clinical studies have not shown such promalignancy effects. However, most such clinical studies have involved patients also treated with concurrent chemotherapy highlighting the possibility that chemotherapy may prevent any potential promalignancy effect caused by an antiangiogenic drug treatment. The impact of antiangiogenic therapy using DC101, an antibody targeting mouse VEGFR-2 with or without concurrent chemotherapy was assessed in multiple human breast cancer xenograft models, where impact on orthotopic primary tumors was evaluated. Metastasis was also assessed during adjuvant and neoadjuvant plus adjuvant therapy, after surgical resection of primary tumors, with the same combination therapies. Antiangiogenic therapy, while blunting tumor volume growth, was found to increase local invasion in multiple primary tumor models, including a patient-derived xenograft, but this effect was blocked by concurrent chemotherapy. Similarly, the combination of paclitaxel with DC101 caused a marked reduction of micro- or macrometastatic disease in contrast to DC101 monotherapy, which was associated with small increases in metastatic disease. Conventional wisdom is that targeted biologic antiangiogenic agents such as bevacizumab when used with chemotherapy increase the efficacy of the chemotherapy treatment. Our results suggest the reverse may be true as well-chemotherapy may improve the impact of antiangiogenic drug treatment and, as a result, overall efficacy. Clin Cancer Res; 21(24); 5488-98. ©2015 AACR. ©2015 American Association for Cancer Research.

A guided interview process to improve student pharmacists' identification of drug therapy problems.

PubMed

Rovers, John; Miller, Michael J; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

2011-02-10

To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems.

A Guided Interview Process to Improve Student Pharmacists' Identification of Drug Therapy Problems

PubMed Central

Miller, Michael J.; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

2011-01-01

Objective To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Methods Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Results Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. Conclusions The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems. PMID:21451770

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol.

PubMed

Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

2016-06-01

Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI -0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

PubMed Central

Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W.; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H.; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

2016-01-01

Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. PMID:26903532

Benefits of adjuvant chemotherapy in high-grade gliomas.

PubMed

DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

PubMed

de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

2015-01-01

Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

SPR741, an Antibiotic Adjuvant, Potentiates the In Vitro and In Vivo Activity of Rifampin against Clinically Relevant Extensively Drug-Resistant Acinetobacter baumannii.

PubMed

Zurawski, Daniel V; Reinhart, Alexandria A; Alamneh, Yonas A; Pucci, Michael J; Si, Yuanzheng; Abu-Taleb, Rania; Shearer, Jonathan P; Demons, Samandra T; Tyner, Stuart D; Lister, Troy

2017-12-01

Acinetobacter baumannii is responsible for 10% of all nosocomial infections and has >50% mortality rates when causing ventilator-associated pneumonia. In this proof-of-concept study, we evaluated SPR741, an antibiotic adjuvant that permeabilizes the Gram-negative membrane, in combination with rifampin against AB5075, an extensively drug-resistant (XDR) A. baumannii strain. In standard in vitro assays and in a murine pulmonary model, we found that this drug combination can significantly reduce bacterial burden and promote animal survival despite an aggressive infection. Copyright © 2017 Zurawski et al.

The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

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

Rusthoven, Chad G., E-mail: Chad.Rusthoven@ucdenver.edu; Carlson, Julie A.; Waxweiler, Timothy V.

Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overallmore » survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of

Letrozole in the extended adjuvant setting: MA.17

PubMed Central

2007-01-01

Relapse after completing adjuvant tamoxifen therapy is a persistent threat for women with hormone-responsive breast cancer. Third-generation aromatase inhibitors, such as letrozole, provide a new option for extended adjuvant hormonal therapy after 5 years of tamoxifen. MA.17 was conducted to determine whether letrozole improves outcome after discontinuation of tamoxifen. Postmenopausal women with hormone receptor-positive breast cancer (N = 5,187) were randomized to letrozole 2.5 mg or placebo once daily for 5 years. At a median follow-up of 30 months, letrozole significantly improved disease-free survival (DFS; P < 0.001), the primary end point, compared with placebo (hazard ratio [HR] for recurrence or contralateral breast cancer 0.58; 95% confidence interval [CI] 0.45, 0.76] P < 0.001). Furthermore, letrozole significantly improved distant DFS (HR = 0.60; 95% CI 0.43, 0.84; P = 0.002) and, in women with node-positive tumors, overall survival (HR = 0.61; 95% CI 0.38, 0.98; P = 0.04). Clinical benefits, including an overall survival advantage, were also seen in women who crossed over from placebo to letrozole after unblinding, indicating that tumors remain sensitive to hormone therapy despite a prolonged period since discontinuation of tamoxifen. The efficacy and safety of letrozole therapy beyond 5 years is being assessed in a re-randomization study, following the emergence of new data suggesting that clinical benefit correlates with the duration of letrozole. MA.17 showed that letrozole is extremely well-tolerated relative to placebo. Letrozole should be considered for all women completing tamoxifen; new results from the post-unblinding analysis suggest that letrozole treatment should also be considered for all disease-free women for periods up to 5 years following completion of adjuvant tamoxifen. PMID:17912635

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

PubMed

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

PubMed Central

Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

2016-01-01

Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

Nanomedicine of synergistic drug combinations for cancer therapy – strategies and perspectives

PubMed Central

Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

2016-01-01

Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. PMID:27287891

Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

PubMed

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

2010-04-07

Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

Can psychedelic compounds play a part in drug dependence therapy?

PubMed

Sessa, Ben; Johnson, Matthew W

2015-01-01

After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area. Royal College of Psychiatrists.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

PubMed

Shiyanbola, Oyewale O; Sprague, Brian L; Hampton, John M; Dittus, Kim; James, Ted A; Herschorn, Sally; Gangnon, Ronald E; Weaver, Donald L; Trentham-Dietz, Amy

2016-09-15

The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society. © 2016 American Cancer Society.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

PubMed

Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer

PubMed Central

Wojcieszek, Piotr; Białas, Brygida

2012-01-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years. PMID:23378855

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.

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%.

Designing liposomal adjuvants for the next generation of vaccines.

PubMed

Perrie, Yvonne; Crofts, Fraser; Devitt, Andrew; Griffiths, Helen R; Kastner, Elisabeth; Nadella, Vinod

2016-04-01

Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and composition allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chemical characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addition of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manufacture of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

[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.

Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma.

PubMed

Berruti, Alfredo; Grisanti, Salvatore; Pulzer, Alina; Claps, Mélanie; Daffara, Fulvia; Loli, Paola; Mannelli, Massimo; Boscaro, Marco; Arvat, Emanuela; Tiberio, Guido; Hahner, Stefanie; Zaggia, Barbara; Porpiglia, Francesco; Volante, Marco; Fassnacht, Martin; Terzolo, Massimo

2017-04-01

In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC). We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up. One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2). The primary aim was RFS, the secondary was overall survival. An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status. Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation. Copyright © 2017 by the Endocrine Society

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.

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

PubMed

Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

2017-01-20

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

A pilot randomized controlled trial of D-cycloserine and distributed practice as adjuvants to constraint-induced movement therapy after stroke.

PubMed

Nadeau, Stephen E; Davis, Sandra E; Wu, Samuel S; Dai, Yunfeng; Richards, Lorie G

2014-01-01

Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 × 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either. © The Author(s) 2014.

Target therapy: new drugs or new combinations of drugs in malignant pleural mesothelioma.

PubMed

Zucali, Paolo A

2018-01-01

Malignant pleural mesothelioma (MPM) is a disease with a poor prognosis due to its aggressive nature. The management of patients with MPM is controversial. Considering that the contribution of surgery and radiation therapy in the management of this disease is not yet established, systemic treatments are predominantly considered during the course of MPM. Unfortunately, the currently therapeutic armamentarium is scarce and its outcomes still appear modest. New treatment strategies are needed. In preclinical setting, cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis pathways involved in the development of MPM have been identified. However, in clinical setting, several drugs targeting these pathways resulted without a significant activity. A deeper knowledge of the biology and pathogenesis of this disease is required to develop more effective tools for diagnosis, therapy and prevention. This paper reviews therapeutic advances in MPM, with a particular focus on new drugs and new association of drugs of target therapy.

Decision-making by surgeons about referral for adjuvant therapy for patients with non-small-cell lung, breast or colorectal cancer: a qualitative study

PubMed Central

Urquhart, Robin; Kendell, Cynthia; Buduhan, Gordon; Rayson, Daniel; Sargeant, Joan; Johnson, Paul; Grunfeld, Eva; Porter, Geoffrey A.

2016-01-01

Background: Because surgeons are the main gatekeepers to oncology services, understanding how they make decisions related to referral for adjuvant therapies is important to optimize referral rates and use of oncology services for patients with potentially curable disease. We examined decision-making by surgeons related to referral to oncology services for patients having undergone curative-intent surgery for non-small-cell lung, breast or colorectal cancer. Methods: We conducted a qualitative study, whose design was guided by the principles of grounded theory. Semi-structured interviews were held with 29 surgeons who performed non-small-cell lung, breast or colorectal cancer surgery in the province of Nova Scotia. Data were collected and analyzed concurrently. Analysis involved an inductive, grounded approach using constant comparative analysis. Data collection and analysis continued until theoretical saturation was reached. Results: Seven factors influenced the surgeons' decision-making related to referral to oncology services: indications and contraindications for therapy; patients' beliefs and preferences; a belief that oncologists are the experts; knowledge of local standards of care; consultation with oncology colleagues; navigating patient logistics (e.g., lodging, caregiving responsibilities, insurance coverage); and system resources and capacity. Interpretation: Our study's findings provide a novel understanding of how surgeons make decisions about oncology referral and point to potential areas for intervention to promote referral to oncology services for patients for whom adjuvant therapy is recommended. PMID:27570760

Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women

PubMed Central

Scharl, A.; Salterberg, A.

2016-01-01

Ovarian function suppression (OFS) for treating breast cancer in pre-menopausal women was introduced for the first time in the late 19th century as bilateral oophorectomy. It was not until the 1960s that the oestrogen receptor was identified and a test for detecting endocrine sensitivity of the breast cancer was developed. A weakness of early trials on OFS for breast cancer treatment is therefore their failure to take receptor sensitivity into account when selecting participants. A meta-analysis performed in the early 1990s first proved that adjuvant OFS significantly improved the cure rate of oestrogen receptor-positive breast cancer in pre-menopausal women regardless of whether it was carried out through oophorectomy, radiation-induced ablation or drug therapy. In the 1970s, tamoxifen was synthesized. It became one of the most important cancer drugs and today constitutes the gold standard for endocrine adjuvant therapy. Taking tamoxifen for a five-year period lowers mortality by 30 % over 15 years. Ten years of tamoxifen therapy reduces mortality even further, with increased side effects, however. Research over the past ten years has proven that for post-menopausal women, aromatase inhibitors have benefits over tamoxifen. Current trial results have rekindled the debate about the combination of OFS with tamoxifen or with aromatase inhibitors for adjuvant breast cancer treatment of pre-menopausal women. These trials have reported an improvement in disease-free survival in patients with a high risk of recurrence when they are treated with a combination of OFS plus tamoxifen or aromatase inhibitors, especially in women younger than 35. However, combination therapy causes significantly more side effects, which could negatively impact compliance. Endocrine treatments administered over a period of many years show waning compliance, which tends to be only around 50 % after five years. Inadequate compliance compromises efficacy and increases the risk of mortality. For

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

PubMed Central

Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

PubMed

Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

Redefining the Positive Margin in Pancreatic Cancer: Impact on Patterns of Failure, Long-Term Survival and Adjuvant Therapy.

PubMed

Osipov, Arsen; Nissen, Nicholas; Rutgers, Joanne; Dhall, Deepti; Naziri, Jason; Chopra, Shefali; Li, Quanlin; Hendifar, Andrew Eugene; Tuli, Richard

2017-11-01

There is debate regarding the definition and clinical significance of margin clearance in pancreatic ductal adenocarcinoma (PDA). A comprehensive archival analysis of surgical resection margins was performed to determine the effect on locoregional recurrence and survival, and the impact of adjuvant therapy in PDA. We identified 105 patients with resected PDA. Pancreatic, anterior, bile duct, and posterior surgical resection margins (PM; posterior surface, uncinate and vascular groove) were identified. Three pathologists reviewed all archival surgical specimens and recategorized each margin as tumor at ink/transected, <0.5, 0.5-1, >1-2, or >2 mm from the inked surface. The impact of these and other clinical variables was assessed on local control, disease-free survival (DFS), and overall survival (OS). Among all margins, PM clearance up to 2 mm was prognostic of DFS (p = 0.01) and OS (p = 0.01). Dichotomizing the PM at 2 mm revealed it to be an independent predictor of local recurrence-free survival [hazard ratio HR] 0.20, 95% confidence interval [CI] 0.048-0.881, p = 0.033), DFS (HR 0.46, 95% CI 0.22-0.96, p = 0.03), and OS (HR 0.31, 95% CI 0.14-0.74, p = 0.008). A margin status of >2 mm was also prognostic of OS in patients who received adjuvant chemotherapy (HR 0.31, 95% CI 0.11-0.89, p = 0.03), however this difference was mitigated in patients receiving adjuvant chemoradiotherapy (HR 0.40, 95% CI 0.10-1.58, p = 0.19). These data highlight the clinical significance of the PM and the lack of significance of other resection margins. Clearance in excess of 2 mm should be considered to improve long-term clinical outcomes. The use of adjuvant radiotherapy should be strongly considered in patients with PMs <2 mm.

[Phase II clinical trial of autologous dendritic cell vaccine with immunologic adjuvant in cutaneous melanoma patients].

PubMed

Baldueva, I A; Novik, A V; Moiseenko, V M; Nekhaeva, T L; Danilova, A B; Danilov, A O; Protsenko, S A; Petrova, T Iu; Uleĭskaia, G I; Shchekina, L A; Semenova, A I; Mikhaĭlichenko, T D; Teletaeva, G M; Zhabina, A S; Volkov, N V; Komarov, Iu I

2012-01-01

This paper describes the clinical results and immunologic changes in cutaneous melanoma patients receiving active specific immunotherapy with autologous dendritic cell vaccine (DCV) in combination with cyclophosphamide used as immunologic adjuvant. Twenty eight patients with morphologically verified stage III-IV cutaneous melanoma receiving therapy in N. N. Petrov Research Institute of Oncology between 2008 and 2011 were included in the study. All patients signed an informed consent form. Nineteen patients (67,9%) received DCV in therapeutic setting, 9 (32,1%) received it in adjuvant setting. DCV therapy was well tolerated. No serious adverse events were registered. Frequent adverse events included Grade 1-2 unspecific symptoms (fever, fatigue, flu-like symptoms) observed in 22% patients after 3,5% of vaccinations. In therapeutic settings the use DCV lead to clinical effect (PR+SD) in 36,6% of patients. PR was observed in 5% of (95% CI 0-15%) patients, SD in 31,6% (95% CI 13-56%). Duration of the objective responses was 168-965+days. Addition of immunologic adjuvant (cyclophosphamide 300 mg/m2 IV 2 hours) 3 days before vaccination increased its efficacy. In this patients group (n=12) the therapy lead to clinical benefit in 42% (95% CI 17-69%) of cases, median time to progression was 91 (95% CI 55-126) days. This regimen was selected for adjuvant therapy. In the adjuvant therapy group (n=9) the median time to progression was 112 (95% CI 58-166) days. Immunologic monitoring showed correlation ofT- and B-cell immune response with DCV clinical efficacy (p<0,05), no correlation with delayed hypersensivity reaction was observed (p>0,1). DCV is well tolerated and shows immunological and clinical response in stage III-IV skin melanoma patients.

Coloring brain tumor with multi-potent micellar nanoscale drug delivery system

NASA Astrophysics Data System (ADS)

Chong, Kyuha; Choi, Kyungsun; Kim, EunSoo; Han, Eun Chun; Lee, Jungsul; Cha, Junghwa; Ku, Taeyun; Yoon, Jonghee; Park, Ji Ho; Choi, Chulhee

2012-10-01

Brain tumor, especially glioblastoma multiforme (GBM), is one of the most malignant tumors, which not only demands perplexing treatment approaches but also requires potent and effective treatment modality to deal with recurrence of the tumor. Photodynamic therapy (PDT) is a treatment which has been recommended as a third-level treatment. We are trying to investigate possibility of the PDT as an efficient adjuvant therapeutic modality for the treatment of brain tumor. Inhibition of tumor progression with photosensitizer was verified, in vitro. With micellar nanoscale drug delivery system, localization of the tumor was identified, in vivo, which is able to be referred as photodynamic diagnosis. With consequent results, we are suggesting photodynamic diagnosis and therapy is able to be performed simultaneously with our nanoscale drug delivery system.

Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

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

Schmidt, Martina E., E-mail: m.schmidt@dkfz.de; Meynköhn, Anna; Habermann, Nina

Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research andmore » Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R{sup 2} effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy

Clinical utility of gene expression profiling data for clinical decision-making regarding adjuvant therapy in early stage, node-negative breast cancer: a case report.

PubMed

Schuster, Steven R; Pockaj, Barbara A; Bothe, Mary R; David, Paru S; Northfelt, Donald W

2012-09-10

Breast cancer is the most common malignancy among women in the United States with the second highest incidence of cancer-related death following lung cancer. The decision-making process regarding adjuvant therapy is a time intensive dialogue between the patient and her oncologist. There are multiple tools that help individualize the treatment options for a patient. Population-based analysis with Adjuvant! Online and genomic profiling with Oncotype DX are two commonly used tools in patients with early stage, node-negative breast cancer. This case report illustrates a situation in which the population-based prognostic and predictive information differed dramatically from that obtained from genomic profiling and affected the patient's decision. In light of this case, we discuss the benefits and limitations of these tools.

Cord blood-derived cytokine-induced killer cellular therapy plus radiation therapy for esophageal cancer: a case report.

PubMed

Wang, Liming; Huang, Shigao; Dang, Yazheng; Li, Ming; Bai, Wen; Zhong, Zhanqiang; Zhao, Hongliang; Li, Yang; Liu, Yongjun; Wu, Mingyuan

2014-12-01

Esophageal cancer is a serious malignancy with regards to mortality and prognosis. Current treatment options include multimodality therapy mainstays of current treatment including surgery, radiation, and chemotherapy. Cell therapy for esophageal cancer is an advancing area of research. We report a case of esophageal cancer following cord blood-derived cytokine-induced killer cell infusion and adjuvant radiotherapy. Initially, she presented with poor spirit, full liquid diets, and upper abdominal pain. Through cell therapy plus adjuvant radiotherapy, the patient remitted and was self-reliant. Recognition of this curative effect of sequent therapy for esophageal cancer is important to enable appropriate treatment. This case highlights cord blood-derived cytokine-induced killer cell therapy significantly alleviates the adverse reaction of radiation and improves the curative effect. Cell therapy plus adjuvant radiotherapy can be a safe and effective treatment for esophageal cancer.

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

Adherence and drug resistance: predictions for therapy outcome.

PubMed Central

Wahl, L M; Nowak, M A

2000-01-01

We combine standard pharmacokinetics with an established model of viral replication to predict the outcome of therapy as a function of adherence to the drug regimen. We consider two types of treatment failure: failure to eliminate the wild-type virus, and the emergence of drug-resistant virus. Specifically, we determine the conditions under which resistance dominates as a result of imperfect adherence. We derive this result for both single- and triple-drug therapies, with attention to conditions which favour the emergence of viral strains that are resistant to one or more drugs in a cocktail. Our analysis provides quantitative estimates of the degree of adherence necessary to prevent resistance. We derive results specific to the treatment of human immunodeficiency virus infection, but emphasize that our method is applicable to a range of viral or other infections treated by chemotherapy. PMID:10819155

Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

PubMed Central

2011-01-01

Background Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Materials and methods Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: "Endometrial cancer", "Endometrial Neoplasms", "Endometrial Neoplasms/radiotherapy", "External beam radiation therapy", "Brachytherapy" and adequate combinations. Conclusion Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer. PMID:22118369

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval.

PubMed

Cohen, Martin H; Johnson, John R; Justice, Robert; Pazdur, Richard

2011-01-01

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.

A Randomized Clinical Trial of Family Therapy in Juvenile Drug Court

PubMed Central

Dakof, Gayle A.; Henderson, Craig E.; Rowe, Cynthia L.; Boustani, Maya; Greenbaum, Paul E.; Wang, Wei; Hawes, Samuel; Linares, Clarisa; Liddle, Howard A.

2016-01-01

The objective of this article is to examine the effectiveness of 2 theoretically different treatments delivered in juvenile drug court—family therapy represented by multidimensional family therapy (MDFT) and group-based treatment represented by adolescent group therapy (AGT)—on offending and substance use. Intent-to-treat sample included 112 youth enrolled in juvenile drug court (primarily male [88%], and Hispanic [59%] or African American [35%]), average age 16.1 years, randomly assigned to either family therapy (n = 55) or group therapy (n = 57). Participants were assessed at baseline and 6, 12, 18 and 24 months following baseline. During the drug court phase, youth in both treatments showed significant reduction in delinquency (average d = .51), externalizing symptoms (average d = 2.32), rearrests (average d = 1.22), and substance use (average d = 4.42). During the 24-month follow-up, family therapy evidenced greater maintenance of treatment gains than group-based treatment for externalizing symptoms (d = 0.39), commission of serious crimes (d = .38), and felony arrests (d = .96). There was no significant difference between the treatments with respect to substance use or misdemeanor arrests. The results suggest that family therapy enhances juvenile drug court outcomes beyond what can be achieved with a nonfamily based treatment, especially with respect to what is arguably the primary objective of juvenile drug courts: reducing criminal behavior and rearrests. More research is needed on the effectiveness of juvenile drug courts generally and on whether treatment type and family involvement influence outcomes. PMID:25621927

Ocular Toxoplasmosis: Therapy-Related Adverse Drug Reactions and Their Management.

PubMed

Helfenstein, M; Zweifel, S; Barthelmes, D; Meier, F; Fehr, J; Böni, C

2017-04-01

Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management. Georg Thieme Verlag KG Stuttgart · New York.

Trajectories of self-reported cognitive function in postmenopausal women during adjuvant systemic therapy for breast cancer.

PubMed

Merriman, John D; Sereika, Susan M; Brufsky, Adam M; McAuliffe, Priscilla F; McGuire, Kandace P; Myers, Jamie S; Phillips, Mary L; Ryan, Christopher M; Gentry, Amanda L; Jones, Lindsay D; Bender, Catherine M

2017-01-01

In a sample of 368 postmenopausal women, we (1) determined within-cohort and between-cohort relationships between adjuvant systemic therapy for breast cancer and self-reported cognitive function during the first 18 months of therapy and (2) evaluated the influence of co-occurring symptoms, neuropsychological function, and other covariates on relationships. We evaluated self-reported cognitive function, using the Patient Assessment of Own Functioning Inventory (PAOFI), and potential covariates (e.g., co-occurring symptom scores and neuropsychological function z-scores) in 158 women receiving aromatase inhibitor (AI) therapy alone, 104 women receiving chemotherapy followed by AI therapy, and 106 non-cancer controls. Patients were assessed before systemic therapy and then every 6 months, for a total of four assessments over 18 months. Controls were assessed at matched time points. Mixed-effects modeling was used to determine longitudinal relationships. Controlling for covariates, patients enrolled before chemotherapy reported poorer global cognitive function (p < 0.001), memory (p < 0.001), language and communication (p < 0.001), and sensorimotor function (p = 0.002) after chemotherapy. These patients reported poorer higher-level cognitive and intellectual functions from before chemotherapy to 12 months after initiation of AI therapy (p < 0.001). Higher levels of depressive symptoms (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.040) at enrollment were predictors of poorer cognitive function over time. PAOFI total score was a predictor of executive function (p = 0.048) and visual working memory (p = 0.005) z-scores, controlling for covariates. Findings provide further evidence of poorer self-reported cognitive function after chemotherapy and of relationships between co-occurring symptoms and cognitive changes. AI therapy alone does not have an impact on self-reported cognitive function. Copyright © 2015 John Wiley

The Influence of Drug Testing and Benefit-Based Distribution of Opioid Substitution Therapy on Drug Abstinence.

PubMed

Gabrovec, Branko

2015-01-01

The objective of our research was to discover whether the new approach to urine drug testing has a positive effect on users' abstinence, users' treatment, and their cooperation, while remaining user-friendly, and whether this approach is more cost-effective. The centers are focused on providing high-quality treatment within a cost-efficient program. In this study, we focus on the influence of drug testing and benefit-based distribution of opioid substitution therapy (BBDOST) on drug abstinence. The purpose of this study was to find any possible positive effect of modified distribution of the therapy and illicit drug testing on the number of users who are abstinent from illicit drugs and users who are not abstinent from illicit drugs as well as the users' opinion on BBDOST and testing. We are also interested in a difference in abstinence rates between those on BBDOST and those not receiving BBDOST. In 2010, the method of drug testing at the center was changed (less frequent and random drug testing) to enable its users faster access to BBDOST (take-home therapy). It was found that the number of drug-abstinent program participants has increased from initial 44.5% (2010) to 54.1% (2014). According to the program participants, the new method allows them to achieve and maintain abstinence from drugs more easily. In addition, they are also satisfied with the modified way of drug testing. This opinion does not change with age, gender, and acquired benefits.

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.

Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta-analysis.

PubMed

Pasquali, Sandro; Yim, Guang; Vohra, Ravinder S; Mocellin, Simone; Nyanhongo, Donald; Marriott, Paul; Geh, Ju Ian; Griffiths, Ewen A

2017-03-01

This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. The optimal treatment for resectable esophageal cancer is unknown. A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.

Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats.

PubMed

Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Rotkvic, I; Mise, S; Zoricic, I; Konjevoda, P; Perovic, D; Simicevic, V; Separovic, J; Hanzevacki, M; Ljubanovic, D; Artukovic, B; Bratulic, M; Tisljar, M; Rekic, B; Gjurasin, M; Miklic, P; Buljat, G

1997-01-01

Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted. Consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesions was simultaneously studied in rats. In gastrointestinal lesions (indomethacin (30 mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 micrograms or 10 ng/kg i.p.) was regularly given simultaneously and/or 1 h prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0.2 mL of Freund's adjuvant) studies (14 days, 30 days, 1 year) BPC 157 (10 micrograms or 10 ng/kg i.p.), it was given as a single application (at 1 h either before or following the application of Freund's adjuvant) or in a once daily regimen (0-14th day, 14-30th day, 14th day-1 year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesion's development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BPC 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after 2 weeks of medication and it could be clearly seen also after 1 year of application. Taking together all these results, the data likely point to a special anti-inflammatory and mucosal integrity protective effect.

DNA nanostructure-based drug delivery nanosystems in cancer therapy.

PubMed

Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

2017-11-25

DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Intranasal hydroxypropyl-β-cyclodextrin-adjuvanted influenza vaccine protects against sub-heterologous virus infection.

PubMed

Kusakabe, Takato; Ozasa, Koji; Kobari, Shingo; Momota, Masatoshi; Kishishita, Natsuko; Kobiyama, Kouji; Kuroda, Etsushi; Ishii, Ken J

2016-06-08

Intranasal vaccination with inactivated influenza viral antigens is an attractive and valid alternative to currently available influenza (flu) vaccines; many of which seem to need efficient and safe adjuvant, however. In this study, we examined whether hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used pharmaceutical excipient to improve solubility and drug delivery, can act as a mucosal adjuvant for intranasal flu vaccines. We found that intranasal immunization of mice with hemagglutinin split- as well as inactivated whole-virion influenza vaccine with HP-β-CD resulted in secretion of antigen-specific IgA and IgGs in the airway mucosa and the serum as well. As a result, both HP-β-CD adjuvanted-flu intranasal vaccine protected mice against lethal challenge with influenza virus, equivalent to those induced by experimental cholera toxin-adjuvanted ones. Of note, intranasal use of HP-β-CD as an adjuvant induced significantly lower antigen-specific IgE responses than that induced by aluminum salt adjuvant. These results suggest that HP-β-CD may be a potent mucosal adjuvant for seasonal and pandemic influenza vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current drug therapy for rheumatoid arthritis.

PubMed

Kawai, Shinichi

2003-01-01

The etiology of rheumatoid arthritis (RA) remains unclear at present, but advances have been made in the drug therapy for RA. Recent attention has been focused on selective cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit a subtype of cyclooxygenase. Various clinical studies have confirmed that the selective COX-2 inhibitors cause fewer severe gastrointestinal complications, although an increased incidence of myocardial infarction was suggested. Terminal enzymes of the arachidonic acid cascade, such as membrane-associated prostaglandin E synthase, might be a target for new NSAIDs in the near future. Low-dose glucocorticoid treatment for RA has been reconsidered possibly to prevent articular destruction of RA. Special attention for glucocorticoid-induced osteoporosis by concomitant administration of bisphosphonates might be necessary. Disease-modifying antirheumatic drugs should be effective in delaying the progression of joint destruction and physical disability. Methotrexate, sulfasalazine, and leflunomide have shown such an effect. Inhibition of articular destruction was also proven by administration of the biologic agents etanercept and infliximab plus methotrexate. Tuberculosis complicated with infliximab therapy is one of the most important concerns in Japan. Agents that improve the quality of life of patients with RA are still needed.

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.

Magnesium sulfate in pediatric anesthesia: the Super Adjuvant.

PubMed

Eizaga Rebollar, Ramón; García Palacios, María V; Morales Guerrero, Javier; Torres, Luis M

2017-05-01

Magnesium is an essential chemical element in all organisms, intervening in most cellular enzymatic reactions; thus, its importance in homeostasis and as a therapeutic tool in highly challenging patients such as pediatrics. The primary purpose of this paper was to review the role of magnesium sulfate as an adjuvant drug in pediatric anesthesia. This compound already has the scientific backing in certain aspects such as analgesia or muscle relaxation, but only theoretical or empirical backing in others such as organ protection or inflammation, where it seems to be promising. The multitude of potential applications in pediatric anesthesia, its high safety, and low cost make magnesium sulfate could be considered a Super Adjuvant. © 2017 John Wiley & Sons Ltd.

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.

Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3.

PubMed

Taper, Henryk S

2008-01-01

The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients.

Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.

PubMed

van de Water, Willemien; Fontein, Duveken B Y; van Nes, Johanna G H; Bartlett, John M S; Hille, Elysée T M; Putter, Hein; Robson, Tammy; Liefers, Gerrit-Jan; Roumen, Rudi M H; Seynaeve, Caroline; Dirix, Luc Y; Paridaens, Robert; Kranenbarg, Elma Meershoek-Klein; Nortier, Johan W R; van de Velde, Cornelis J H

2013-01-01

Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003). Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Approval Summary: Letrozole (Femara® Tablets) for Adjuvant and Extended Adjuvant Postmenopausal Breast Cancer Treatment: Conversion of Accelerated to Full Approval

PubMed Central

Johnson, John R.; Justice, Robert; Pazdur, Richard

2011-01-01

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor–positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76–1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen. PMID:22089970

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.

Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

PubMed

Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

2015-03-01

Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

Does adjuvant radiotherapy suppress liver regeneration after partial hepatectomy?

PubMed

Choi, Jin-Hwa; Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W

2009-05-01

To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 +/- 38.3cm(3) and 81.5 +/- 75.6cm(3), respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.

Neoadjuvant trials in ER+ breast cancer: A tool for acceleration of drug development and discovery

PubMed Central

Guerrero-Zotano, Angel L.; Arteaga, Carlos L.

2017-01-01

Neoadjuvant therapy trials offer an excellent strategy for drug development and discovery in breast cancer, particularly in triple negative and HER2-overexpressing subtypes, where pathologic complete response is a good surrogate of long term patient benefit. For estrogen receptor (ER)-positive breast cancers, however, use of this strategy has been challenging because of the lack of validated surrogates of long term efficacy and the overall good prognosis of the majority of patients with this cancer subtype. We review below the clinical benefits of neodjuvant endocrine therapy for ER+/HER2-negative breast cancer, its use and limitations for drug development, prioritization of adjuvant and metastatic trials, and biomarker discovery. PMID:28495849

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.

Magnetic Nanomaterials for Hyperthermia-based Therapy and Controlled Drug Delivery

PubMed Central

Kumar, Challa S. S. R.; Mohammad, Faruq

2011-01-01

Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “Hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled Drug delivery through Bond Breaking (DBB) and Hyperthermia-based controlled Drug delivery through Enhanced Permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities in the combination of hyperthermia-based therapy and controlled drug release paradigms for successful application in personalized medicine. PMID:21447363

Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

PubMed Central

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients. PMID:26075241

Immunoendocrine interactions during HIV-TB coinfection: implications for the design of new adjuvant therapies.

PubMed

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo; Quiroga, Maria Florencia

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-06-01

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-08-11

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

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.

Liposomal Drug Delivery System for Cancer Therapy: Advancement and Patents.

PubMed

Jha, Sheetal; Sharma, Pramod K; Malviya, Rishabha

2016-01-01

In this review article, authors reviewed about the liposomes which are amongst various drug delivering systems for the delivery of the therapeutic agents at the target site. Advances in liposomal drug delivery systems for the cancer therapy have enhanced the therapeutic levels of the anticancer moieties. Liposomes show promising action on the tumor by incorporating less amount of drug at the target site, with minimum toxic effect and maximum therapeutic effect and thereby enhancing the bioavailability. Liposome-based drug delivery systems provide the potential to elevate the effect of drug concentration in tumor cells. Manuscript briefly describes the role of liposomes in cancer therapy and various patents based on the same. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mechanisms of, and Adjuvants for, Bone Pain.

PubMed

Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

2018-06-01

Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

Biopolymers as transdermal drug delivery systems in dermatology therapy.

PubMed

Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

2010-01-01

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

PubMed

Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

2017-06-01

This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

Psychosocial influences on suboptimal adjuvant breast cancer treatment adherence among African American women: implications for education and intervention.

PubMed

Magai, Carol; Consedine, Nathan S; Adjei, Brenda A; Hershman, Dawn; Neugut, Alfred

2008-12-01

Despite lower incidence, African American women are at increased risk of dying from breast cancer relative to their European American counterparts. Although there are key differences in both screening behavior and tumor characteristics, an additional part of this mortality difference may lie in the fact that African American women receive suboptimal adjuvant chemotherapy and may receive suboptimal hormonal therapy, therapies that are known to increase survival. The authors consider ethnic differences in the psychosocial factors that have been shown to relate to poor screening adherence and consider how they may influence adherence to breast cancer adjuvant treatment, thus the receipt of suboptimal adjuvant chemo or hormonal therapy. To this end, they review ethnic differences in cognitive, emotional, and social network variables. Psychosocial variables should be included in research designed to understand cancer disparities as well interventions that can be tailored to culturally diverse populations to improve treatment adherence.

Rescue of Graves Thyrotoxicosis-Induced Cholestatic Liver Disease Without Antithyroid Drugs: A Case Report.

PubMed

Yan, Lily D; Thomas, Dylan; Schwartz, Michael; Reich, Jason; Steenkamp, Devin

2017-03-01

Graves thyrotoxicosis rarely presents with painless jaundice resulting from hyperthyroidism-associated hepatotoxicity, without preexisting liver disease. Management in patients with this presentation is challenging, given that the thionamides, methimazole and propylthiouracil, have both been associated with drug-induced liver injury. Radioactive iodine ablation and thyroidectomy are well-established alternatives, but each have their associated risks and contraindications. We present an unusual case of severe hyperthyroidism-associated hepatotoxicity, in which adjuvant therapies, including glucocorticoids, saturated solution of potassium iodide, and cholestyramine, were used as a bridge to definitive therapy with thyroidectomy.

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

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

Optimal control of malaria: combining vector interventions and drug therapies.

PubMed

Khamis, Doran; El Mouden, Claire; Kura, Klodeta; Bonsall, Michael B

2018-04-24

The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes. An optimal control framework based on coupled models of mosquito population dynamics and malaria epidemiology is used to investigate the cost-effectiveness of combining vector control with drug therapies in homogeneous environments with and without vector migration. The costs of endemic malaria are weighed against the costs of administering artemisinin therapies and releasing modified mosquitoes using various cost structures. Larval density dependence is shown to reduce the cost-effectiveness of conventional sterile insect releases compared with transgenic mosquitoes with a late-acting lethal gene. Using drug treatments can reduce the critical vector control release ratio necessary to cause disease fadeout. Combining vector control and drug therapies is the most effective and efficient use of resources, and using optimized implementation strategies can substantially reduce costs.

An outline of main factors of drug resistance influencing cancer therapy.

PubMed

Frączek, Natalia; Bronisz, Iwona; Pietryka, Magdalena; Kępińska, Dorota; Strzała, Patrycja; Mielnicka, Kamila; Korga, Agnieszka; Dudka, Jaroslaw

2016-12-01

Drug resistance in cancer therapy is a multifactorial phenomenon that determines remission or progression. It is known that resistance to used anticancer drugs may be the consequence of drug transport to the cell or intracellular distribution. It may also be the result of its molecular target structural change, apoptosis inhibition or increase in some enzymes activity, e.g. pentose phosphate pathway enzymes. Intrinsic (pre-existed) drug resistance is related to the phenotype of cancer as well as normal cells. Acquired, after partial administration of chemotherapy, type of drug resistance in addition to the starting phenotype is closely linked to the development of new more aggressive clones and adaptive processes. In both, the intrinsic and acquired resistance, role play also mutations. These may be partially spontaneous, but in terms of acquired resistance, they are mostly induced by the exposure to the drugs. The article mentions some traditional mechanisms related to the acquisition of resistance by cancer cells during therapy, through the protein transporters, apoptosis deregulation, angiogenesis and the impact of the tumour microenvironment. We focused however on some more alternative ways of therapy resistance, such as, hypoxia and tumour acidification, cancer stem cells (CSCs), exosomes and radiotherapy resistance. A concise summary of the drug resistance presented in the paper may be an important aspect in studies to increase the effectiveness of cancer therapies.

Parallel Demand-Withdraw Processes in Family Therapy for Adolescent Drug Abuse

PubMed Central

Rynes, Kristina N.; Rohrbaugh, Michael J.; Lebensohn-Chialvo, Florencia; Shoham, Varda

2013-01-01

Isomorphism, or parallel process, occurs in family therapy when patterns of therapist-client interaction replicate problematic interaction patterns within the family. This study investigated parallel demand-withdraw processes in Brief Strategic Family Therapy (BSFT) for adolescent drug abuse, hypothesizing that therapist-demand/adolescent-withdraw interaction (TD/AW) cycles observed early in treatment would predict poor adolescent outcomes at follow-up for families who exhibited entrenched parent-demand/adolescent-withdraw interaction (PD/AW) before treatment began. Participants were 91 families who received at least 4 sessions of BSFT in a multi-site clinical trial on adolescent drug abuse (Robbins et al., 2011). Prior to receiving therapy, families completed videotaped family interaction tasks from which trained observers coded PD/AW. Another team of raters coded TD/AW during two early BSFT sessions. The main dependent variable was the number of drug use days that adolescents reported in Timeline Follow-Back interviews 7 to 12 months after family therapy began. Zero-inflated Poisson (ZIP) regression analyses supported the main hypothesis, showing that PD/AW and TD/AW interacted to predict adolescent drug use at follow-up. For adolescents in high PD/AW families, higher levels of TD/AW predicted significant increases in drug use at follow-up, whereas for low PD/AW families, TD/AW and follow-up drug use were unrelated. Results suggest that attending to parallel demand-withdraw processes in parent/adolescent and therapist/adolescent dyads may be useful in family therapy for substance-using adolescents. PMID:23438248

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

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

Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no; Department of Oncology, Haukeland University Hospital, Bergen; Engellau, Jacob

2013-08-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence intervalmore » [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.« less

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs - provision of due diligence in the treatment process.

PubMed

Zajdel, Justyna; Zajdel, Radosław

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.

[Music as an adjuvant treatment for anxiety in pediatric oncologic patients].

PubMed

Sepúlveda-Vildósola, Ana Carolina; Herrera-Zaragoza, Octavio René; Jaramillo-Villanueva, Leonel; Anaya-Segura, Armando

2014-01-01

Music has been used as adjuvant therapy for anxiety and it is based on scientific principles. Tone, rhythm, harmony and time are crucial for its efficacy. Chemotherapy treatment frequently produces important stress in pediatric patients. This may delay treatment occasionally. Our objective was to determine if adjuvant therapy with music reduces anxiety in pediatric oncologic patients under ambulatory chemotherapy. Time series design. We included patients from 8 to 16 years of age who received ambulatory intravenous chemotherapy at the Hospital de Pediatría, Centro Médico Nacional Siglo XXI. They received treatment as usual on the first day, and music therapy during the second day of chemotherapy. A visual scale was used to categorize the level of anxiety prior and after treatment on both days. We included 22 patients. All patients experienced both moderate and high levels of anxiety prior to chemotherapy treatment on both days. There was a statistically significant reduction of anxiety on both groups after chemotherapy, but with lower levels of anxiety in the intervention group. There is an additional benefit with the use of music therapy in the reduction of anxiety in pediatric patients who receive ambulatory chemotherapy.

Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

PubMed

Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

2013-06-01

In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and

Alginate Particles with Ovalbumin (OVA) Peptide Can Serve as a Carrier and Adjuvant for Immune Therapy in B16-OVA Cancer Model.

PubMed

Zhu, Longbao; Ge, Fei; Yang, Liangjun; Li, Wanzhen; Wei, Shenghua; Tao, Yugui; Du, Guocheng

2017-04-28

BACKGROUND Alginate is a natural polysaccharide obtained from brown algae and has been shown to have numerous applications in biomedical science, such as wound healing, delivery of bioactive agents, and cell transplantation. Ovalbumin (OVA) peptide 323-339 has been reported to be involved in immune response.  MATERIAL AND METHODS This work investigated the use of alginate particles as a carrier and adjuvant for the immune therapy of cancer. Alginate particles loaded with OVA peptide were produced via emulsion. A tumor model was established in C57BL/6J mice via subcutaneous injection of 3×105 B16-OVA tumor cells. The effect of alginate/OVA peptide on cell viability was analyzed by use of the CCK-8 assay kit. Activation of macrophages was examined by checking cell surface makers CD40 and CD86 by FACs. RESULTS Alginate/OVA peptide inhibited tumor progression more effectively than using the peptide alone. The viability and uptake study illustrated that this particle is safe and non-toxic. The activation study demonstrated that alginate particles can promote the activation of surface markers on macrophages. ELISA assay showed that the particles with peptide can promote the secretion of inflammatory and effector cytokines from macrophages.  CONCLUSIONS This study demonstrated that alginate has dual functions in immune therapy of cancer, serving both as a carrier and an adjuvant.

21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

Code of Federal Regulations, 2010 CFR

2010-04-01

... foamed plastics. 178.3010 Section 178.3010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... substances used in the manufacture of foamed plastics. The following substances may be safely used as adjuvants in the manufacture of foamed plastics intended for use in contact with food, subject to any...

A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.

PubMed

Cox, Georgina; Sieron, Arthur; King, Andrew M; De Pascale, Gianfranco; Pawlowski, Andrew C; Koteva, Kalinka; Wright, Gerard D

2017-01-19

Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

PubMed

Ge, Yanxiu; Ma, Yakun; Li, Lingbing

2016-10-01

Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. Copyright © 2016 Elsevier B.V. All rights reserved.

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

D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia.

PubMed

Rosse, R B; Fay-McCarthy, M; Kendrick, K; Davis, R E; Deutsch, S I

1996-10-01

This preliminary investigation examined the therapeutic efficacy of two doses of oral D-cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D-Cycloserine is an agonist at the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor complex. An NMDA agonist intervention was studied because of the schizophreniform psychosis precipitated by phencyclidine (PCP), which is a noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of schizophrenia is regarded as the most comprehensive pharmacological model of this disorder. In this preliminary, placebo-controlled, double-blind, parallel-group study, the measures of treatment efficacy were the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and Clinical Global Impression Scale. The final scores for each item of the outcome measures employed were based on the consensus of at least two trained raters who were present during each rating interview. In the 13 subjects evaluated, although the D-cycloserine was well tolerated, neither dose seemed to possess adjuvant therapeutic efficacy. However, since another recent report of nine patients with schizophrenia treated for 2 weeks with a slightly higher dose of D-cycloserine (50 mg/day) described significant clinical and neuropsychological improvement, further study of the adjuvant potential of slightly higher doses of D-cycloserine seems warranted. Additionally, there might be a therapeutic window for D-cycloserine dosing, as daily doses of 250 mg have been associated with symptom worsening.

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.

Influence of particle size, an elongated particle geometry, and adjuvants on dendritic cell activation.

PubMed

Mathaes, Roman; Winter, Gerhard; Siahaan, Teruna J; Besheer, Ahmed; Engert, Julia

2015-08-01

Modern subunit vaccines have many benefits compared to live vaccines such as convenient and competitive large scale production, better reproducibility and safety. However, the poor immunogenicity of subunit vaccines usually requires the addition of potent adjuvants or drug delivery vehicles. Accordingly, researchers are investigating different adjuvants and particulate vaccine delivery vehicles to boost the immunogenicity of subunit vaccines. Despite the rapidly growing knowledge in this field, a comparison of different adjuvants is sparsely found. Until today, little is known about efficient combinations of the different adjuvants and particulate vaccine delivery vehicles. In this study we compared three adjuvants with respect to their immune stimulatory potential and combined them with different particulate vaccine delivery vehicles. For this reason, we investigated two types of polyI:C and a CL264 base analogue and combined these adjuvants with differently sized and shaped particulate vaccine delivery vehicles. A high molecular weight polyI:C combined with a spherical nano-sized particulate vaccine delivery vehicle promoted the strongest dendritic cells activation. Copyright © 2015 Elsevier B.V. All rights reserved.

Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

PubMed Central

Saruwatari, Junji; Ishitsu, Takateru; Nakagawa, Kazuko

2010-01-01

Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed. PMID:27713373

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

PubMed

Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

2010-01-25

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

2016-03-01

invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive disease-free survival rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [<1%] vs grade 3, n=23 [2%] in the placebo group), vomiting (grade 3, n=47 [3%] vs n=5 [<1%]), and nausea (grade 3, n=26 [2%] vs n=2 [<1%]). QT prolongation occurred in 49 (3%) patients given neratinib and 93 (7%) patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 (1%) and 15 (1%) patients, respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 (6%) patients in the placebo group. Seven (<1%) deaths (four patients in the neratinib group and three patients in the placebo group) unrelated to disease progression occurred after study drug discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were attributed to study treatment in either group. Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer. Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained. Wyeth, Pfizer, Puma Biotechnology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Access to artemisinin-based combination therapies and other anti-malarial drugs in Kinshasa.

PubMed

Nkoli Mandoko, P; Sinou, V; Moke Mbongi, D; Ngoyi Mumba, D; Kahunu Mesia, G; Losimba Likwela, J; Bi Shamamba Karhemere, S; Muepu Tshilolo, L; Tamfum Muyembe, J-J; Parzy, D

2018-06-01

Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa. We performed a cross-sectional survey of 404 pharmacies. Anti-malarial drugs were stocked in all surveyed pharmacies. Non-artemisinin-based anti-malarial therapies such as quinine or sulfadoxine-pyrimethamine, were the most frequently stocked drugs (93.8% of pharmacies). Artemisinin-based combination therapies were stocked in 88% of pharmacies. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies), but less than 3% were quality-assured products. Other non-officially recommended artemisinin-based therapies including oral monotherapies were widely available. Artemisinin-based combination therapies were widely available in the private pharmacies of Kinshasa. However, the private sector does not guarantee the use of nationally recommended anti-malarial drugs nor does it give priority to quality-assured anti-malarial drugs. These practices contribute to the risk of emergence and spread of resistance to anti-malarial drugs and to increasing treatment costs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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.

Hyaluronan degrading silica nanoparticles for skin cancer therapy

NASA Astrophysics Data System (ADS)

Scodeller, P.; Catalano, P. N.; Salguero, N.; Duran, H.; Wolosiuk, A.; Soler-Illia, G. J. A. A.

2013-09-01

We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human

Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

PubMed

Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

2016-09-01

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

Impact of clinical pharmacist on cost of drug therapy in the ICU

PubMed Central

Aljbouri, Tareq M.; Alkhawaldeh, Mohammed S.; Abu-Rumman, Ala’a eddeen K.; Hasan, Thamer A.; Khattar, Hakeem M.; Abu-Oliem, Atallah S.

2013-01-01

Objective To determine whether the presence of Clinical Pharmacist affects the cost of drug therapy for patients admitted to the Intensive Care Unit (ICU) at Al-Hussein hospital at Royal Medical Services in Amman, Jordan. Method This study compares the consumed quantities of drugs over two periods of time. Each period was ten months long. In the second period there was a Clinical Pharmacist. The decrease in consumption rate of drugs is considered to be an indicator of the success of Clinical Pharmacist in the ICU, as any decrease in consumption rate reflects the correct application of Clinical Pharmacy practices. The cost of this decrease in consumption rate represents the total reduction of drug therapy cost. Results The total reduction of drug therapy cost after applying Clinical Pharmacy practices in the ICU over a period of ten months was 149946.80 JD (211574.90 USD), which represents an average saving of 35.8% when compared to the first period in this study. Conclusion The results of this study showed a significant reduction in the consumed quantities of drugs and therefore a reduction in cost of drug therapy. Such findings highlight the importance of the presence of Clinical Pharmacist in all Jordanian hospitals wards and units. PMID:24227956

21 CFR 172.710 - Adjuvants for pesticide use dilutions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... fatty acids. α-[p-(1,1,3,3-Tetramethylbutyl) phenyl]-omega-hydroxypoly(oxyethylene) produced by the...-Tetramethylbutyl) phenyl]-omega-hydroxypoly(oxyethylene) produced by the condensation of 1 mole of p-(1,1,3,3... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Adjuvants for pesticide use dilutions. 172.710...

21 CFR 172.710 - Adjuvants for pesticide use dilutions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... fatty acids. α-[p-(1,1,3,3-Tetramethylbutyl) phenyl]-omega-hydroxypoly(oxyethylene) produced by the...-Tetramethylbutyl) phenyl]-omega-hydroxypoly(oxyethylene) produced by the condensation of 1 mole of p-(1,1,3,3... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide use dilutions. 172.710...

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs – provision of due diligence in the treatment process

PubMed Central

Zajdel, Justyna

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133

Toxicological Risks of Agrochemical Spray Adjuvants: Organosilicone Surfactants May Not Be Safe

PubMed Central

Mullin, Christopher A.; Fine, Julia D.; Reynolds, Ryan D.; Frazier, Maryann T.

2016-01-01

Agrochemical risk assessment that takes into account only pesticide active ingredients without the spray adjuvants commonly used in their application will miss important toxicity outcomes detrimental to non-target species, including humans. Lack of disclosure of adjuvant and formulation ingredients coupled with a lack of adequate analytical methods constrains the assessment of total chemical load on beneficial organisms and the environment. Adjuvants generally enhance the pesticidal efficacy and inadvertently the non-target effects of the active ingredient. Spray adjuvants are largely assumed to be biologically inert and are not registered by the USA EPA, leaving their regulation and monitoring to individual states. Organosilicone surfactants are the most potent adjuvants and super-penetrants available to growers. Based on the data for agrochemical applications to almonds from California Department of Pesticide Regulation, there has been increasing use of adjuvants, particularly organosilicone surfactants, during bloom when two-thirds of USA honey bee colonies are present. Increased tank mixing of these with ergosterol biosynthesis inhibitors and other fungicides and with insect growth regulator insecticides may be associated with recent USA honey bee declines. This database archives every application of a spray tank adjuvant with detail that is unprecedented globally. Organosilicone surfactants are good stand alone pesticides, toxic to bees, and are also present in drug and personal care products, particularly shampoos, and thus represent an important component of the chemical landscape to which pollinators and humans are exposed. This mini review is the first to possibly link spray adjuvant use with declining health of honey bee populations. PMID:27242985

Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial.

PubMed

Horgan, A M; Darling, G; Wong, R; Guindi, M; Liu, G; Jonker, D J; Lister, J; Xu, W; MacKay, H M; Dinniwell, R; Kim, J; Pierre, A; Shargall, Y; Asmis, T R; Agboola, O; Seely, A J; Ringash, J; Wells, J; Marginean, E C; Haider, M; Knox, J J

2016-11-01

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m 2 ) + Cisplatin (30 mg/m 2 ) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer. © 2015 International Society for Diseases of the Esophagus.

[Coping with HIV infection and motivation for therapy in multi-drug dependent patients].

PubMed

Grube, M

1995-05-01

The intrapsychological process of working through the five stages of death in terminally ill patients (according to Kübler-Ross) was documented by videotaping semistructured interviews. There were 67 i.v. drug-dependent polytoxic HIV-positive inpatients. An inquiry was also made into their social niveau, the course of their addiction, the patients' legal status, and their previous experience with long-term therapy. Prevalent forms of working through the five stages of death could be established with reasonable reliability, and their influence could be determined on how the patients actually made use of offers of long-term therapy. The most important finding was that HIV-positive i.v. drug-addicted polytoxic patients started with a similar ratio of 1:3 in drug-free long-term therapy compared to HIV-negative i.v. drug-addicted polytoxic inpatients (n = 71). In the group of HIV-positive i.v. drug-addicted inpatients their individual means of psychologically working through their illness, their legal status and their previous experience with drug-free long-term therapy seem to be relevant factors in positive therapy motivation. This should be kept in mind when methadone programs are discussed.

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.

PubMed

Long, Georgina V; Hauschild, Axel; Santinami, Mario; Atkinson, Victoria; Mandalà, Mario; Chiarion-Sileni, Vanna; Larkin, James; Nyakas, Marta; Dutriaux, Caroline; Haydon, Andrew; Robert, Caroline; Mortier, Laurent; Schachter, Jacob; Schadendorf, Dirk; Lesimple, Thierry; Plummer, Ruth; Ji, Ran; Zhang, Pingkuan; Mookerjee, Bijoyesh; Legos, Jeff; Kefford, Richard; Dummer, Reinhard; Kirkwood, John M

2017-11-09

Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma. Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI

Antibody–Drug Conjugates for Cancer Therapy

PubMed Central

Parslow, Adam C.; Parakh, Sagun; Lee, Fook-Thean; Gan, Hui K.; Scott, Andrew M.

2016-01-01

Antibody–drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver a linked cytotoxic agent directly into a tumour cell. The development of these compounds provides exciting opportunities for improvements in patient care. Here, we review the key issues impacting on the clinical success of ADCs in cancer therapy. Like many other developing therapeutic classes, there remain challenges in the design and optimisation of these compounds. As the clinical applications for ADCs continue to expand, key strategies to improve patient outcomes include better patient selection for treatment and the identification of mechanisms of therapy resistance. PMID:28536381

Microencapsulation of Drugs: New Cancer Therapies and Improved Drug Delivery Derived from Micro Gravity Research

NASA Technical Reports Server (NTRS)

Morrison, Dennis R.; Haddad, Ruwaida S.

2003-01-01

Experiments on the ISS include encapsulation of several different anti-cancer drugs, magnetic triggering particles, and encapsulation of genetically engineered DNA. Eight experiments, using the MEPS-II apparatus, were conducted to study the limitations of the fluid shear and g-dependent forces. These studies included: 1) formation of anti-tumor microcapsules containing drugs for "Chemoembolization" of vascularized tumors, 2) formation of microcapsules containing a photo-activated drug which can be used for Photo Dynamic Therapy of solid tumors by activation with near infrared light (630 nm), 3) coencapsulation of magnetic trigger particles and anti-tumor drugs, and 4) encapsulation of plasmid DNA. The Microencapsulation Electrostatic Processing System (MEPS-II) is an automated apparatus modified for use in the ISS Express Rack. The process brings together two immiscible liquids, restricting fluid shear to permitting surface tension forces to predominate at the interface of the fluids. Microcapsules were recovered from all 8 experiments and are currently being analyzed for size distribution and drug content. Six NASA Patents have issued from the space research and several more are pending. The preliminary results from the Increment 5 - UF-2 experiments have provided new insight into the best formulations and conditions required to produce microcapsules of different drugs, esp. special capsules containing diagnostic imaging materials and triggered release particles. Co-encapsulation of multiple drugs and Photodynamic Therapy (PDT) drugs has enabled new engineering strategies for production of microcapsules on Earth designed for direct delivery into cancer tissues. Other microcapsules have now been made for treatment of deep tissue infections, clotting disorders, and to provide delivery of genetic engineered materials for potential gene therapy approaches. The MEPS-II apparatus remains in the ISS awaiting microencapsulation experiments to be conducted in micro-g, and

Current trends in immunosuppressive therapies for renal transplant recipients.

PubMed

Lee, Ruth-Ann; Gabardi, Steven

2012-11-15

Current trends in immunosuppressive therapies for renal transplant recipients are reviewed. The common premise for immunosuppressive therapies in renal transplantation is to use multiple agents to work on different immunologic targets. The use of a multidrug regimen allows for pharmacologic activity at several key steps in the T-cell replication process and lower dosages of each individual agent, thereby producing fewer drug-related toxicities. In general, there are three stages of clinical immunosuppression: induction therapy, maintenance therapy, and treatment of an established acute rejection episode. Only immunosuppressive therapies used for maintenance therapy are discussed in detail in this review. The most common maintenance immunosuppressive agents can be divided into five classes: (1) the calcineurin inhibitors (CNIs) (cyclosporine and tacrolimus), (2) costimulation blockers (belatacept), (3) mammalian target of rapamycin inhibitors (sirolimus and everolimus), (4) antiproliferatives (azathioprine and mycophenolic acid derivatives), and (5) corticosteroids. Immunosuppressive regimens vary among transplantation centers but most often include a CNI and an adjuvant agent, with or without corticosteroids. Selection of appropriate immunosuppressive regimens should be patient specific, taking into account the medications' pharmacologic properties, adverse-event profile, and potential drug-drug interactions, as well as the patient's preexisting diseases, risk of rejection, and medication regimen. Advancements in transplant immunosuppression have resulted in a significant reduction in acute cellular rejection and a modest increase in long-term patient and graft survival. Because the optimal immunosuppression regimen is still unknown, immunosuppressant use should be influenced by institutional preference and tailored to the immunologic risk of the patient and adverse-effect profile of the drug.

Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

PubMed

Shinde, Shivani; Gordon, Pamela; Sharma, Prashant; Gross, James; Davis, Mellar P

2015-03-01

Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing. In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected. Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS). This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

PubMed

Borba, Eduardo F; Saad, Carla G S; Pasoto, Sandra G; Calich, Ana L G; Aikawa, Nadia E; Ribeiro, Ana C M; Moraes, Julio C B; Leon, Elaine P; Costa, Luciana P; Guedes, Lissiane K N; Silva, Clovis A A; Goncalves, Celio R; Fuller, Ricardo; Oliveira, Suzimara A; Ishida, Maria A; Precioso, Alexander R; Bonfa, Eloisa

2012-06-01

To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs.

PubMed

Yoon, Nara; Vander Velde, Robert; Marusyk, Andriy; Scott, Jacob G

2018-05-07

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, [Formula: see text] and [Formula: see text], each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for [Formula: see text] and [Formula: see text], we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., [Formula: see text]-long for DrugA and [Formula: see text]-long for DrugB with [Formula: see text] and [Formula: see text]). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, [Formula: see text], and the effect of each drug. We determine a critical ratio, which we term [Formula: see text], at which the two drugs are equally effective. As the first stage of the

Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia.

PubMed

Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo

2016-01-01

Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain.

[Immunosuppressive therapy in dogs and cats. Properties of drugs and their use in various immune-mediated diseases].

PubMed

Rieder, Johanna; Mischke, Reinhard

2018-04-01

Veterinarians are regularly faced with the diagnosis and therapy of immune-mediated diseases. More frequently occurring immune-mediated diseases are immune-mediated hemolytic anemia, immunemediated thrombocytopenia and polyarthritis. Glucocorticoids are commonly used as first-line treatment because of their availability, efficacy and rapid action. Nevertheless, some patients do not respond to glucocorticoid therapy alone. Others require a rapid dose reduction because of severe side effects from glucocorticoid treatment. These patients benefit from adjuvant therapies. Ciclosporin preparations are licensed for use in veterinary medicine. The use of azathioprine, mycophenolate mofetil and human immunoglobulin therapy has also been documented. This article describes the mode of action of certain immunosuppressive agents and their use in selected diseases from recent literature. Schattauer GmbH.

Virginal Breast Hypertrophy: Different Presentations of 2 Cases and the Role of Tamoxifen as an Adjuvant Therapy.

PubMed

Karagüzel, Gülay; Bilen, Sevcan; Karaçal, Naci; Yıldız, Kadriye; Livaoğlu, Murat

2016-10-01

Virginal breast hypertrophy is a rapid and massive enlargement of one or both breasts. There are several proposed causes and treatment options for virginal breast hypertrophy, but the investigations to support these theories are lacking. We report two premenarchal girls with virginal breast hypertrophy who presented as different clinical cases. After their surgical interventions, their clinical courses were followed for more than 2 years with tamoxifen as an adjuvant therapy. Breast size and shape disorders can be a disturbing cosmetic problem for adolescents who worry about their body image. A combination treatment of breast reduction surgery and tamoxifen is reasonable and can eliminate the need for repeated surgeries for girls with virginal breast hypertrophy. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

PubMed

Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

2018-05-01

In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Sonoporation, drug delivery, and gene therapy.

PubMed

Liang, H-D; Tang, J; Halliwell, M

2010-01-01

Ultrasound is a very effective modality for drug delivery and gene therapy because energy that is non-invasively transmitted through the skin can be focused deeply into the human body in a specific location and employed to release drugs at that site. Ultrasound cavitation, enhanced by injected microbubbles, perturbs cell membrane structures to cause sonoporation and increases the permeability to bioactive materials. Cavitation events also increase the rate of drug transport in general by augmenting the slow diffusion process with convective transport processes. Drugs and genes can be incorporated into microbubbles, which in turn can target a specific disease site using ligands such as the antibody. Drugs can be released ultrasonically from microbubbles that are sufficiently robust to circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Local drug delivery ensures sufficient drug concentration at the diseased region while limiting toxicity for healthy tissues. Ultrasound-mediated gene delivery has been applied to heart, blood vessel, lung, kidney, muscle, brain, and tumour with enhanced gene transfection efficiency, which depends on the ultrasonic parameters such as acoustic pressure, pulse length, duty cycle, repetition rate, and exposure duration, as well as microbubble properties such as size, gas species, shell material, interfacial tension, and surface rigidity. Microbubble-augmented sonothrombolysis can be enhanced further by using targeting microbubbles.

Adjuvant Intravesical Bacillus Calmette-Guérin Therapy and Survival Among Elderly Patients With Non–Muscle-Invasive Bladder Cancer

PubMed Central

Spencer, Benjamin A.; McBride, Russell B.; Hershman, Dawn L.; Buono, Donna; Herr, Harry W.; Benson, Mitchell C.; Gupta-Mohile, Supriya; Neugut, Alfred I.

2013-01-01

Purpose: National guidelines recommend adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy for higher-risk non–muscle-invasive bladder cancer (NMIBC). Although a survival benefit has not been demonstrated, randomized trials have shown reduced recurrence and delayed progression after its use. We investigated predictors of BCG receipt and its association with survival for older patients with NMIBC. Patients and Methods: We identified individuals with NMIBC registered in the Surveillance, Epidemiology, and End Results–Medicare database from 1991 to 2003. We used logistic regression to compare those treated with BCG within 6 months of initial diagnosis with those not treated, adjusting for demographic and clinical factors. Cox proportional hazards modeling was used to analyze the association between BCG and overall survival (OS) and bladder cancer–specific survival (BCSS) for the entire cohort and within tumor grades. Results: Of 23,932 patients with NMIBC identified, 22% received adjuvant intravesical BCG. Predictors of receipt were stages Tis and T1, higher grade, and urban residence. Age > 80 years, fewer than two comorbidities, and not being married were associated with decreased use. In the survival analysis, BCG use was associated with better OS (hazard ratio [HR], 0.87; 95% CI, 0.83 to 0.92) in the entire cohort and BCSS among higher-grade cancers (poorly differentiated: HR, 0.78; 95% CI, 0.72 to 0.85; undifferentiated: HR, 0.66; 95% CI, 0.56 to 0.77). Conclusion: Despite guidelines recommending its use, BCG is administered to less than one quarter of eligible patients. This large population-based study found improved OS and BCSS were associated with use of adjuvant intravesical BCG among older patients with NMIBC. Better-designed clinical trials focusing on higher-grade cancers are needed to confirm these findings. PMID:23814517

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

PubMed

El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

2018-01-01

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized study.

PubMed

Nasa, Mukesh; Choksey, Ajay; Phadke, Aniruddha; Sawant, Prabha

2013-11-01

Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. A sequential treatment schedule has been reported to be effective, but studies published to date were performed in Italy. We undertook this study to determine whether these results could be replicated in India. A randomized, open-labeled, prospective controlled trial comparing sequential vs. standard triple-drug therapy was carried out at Lokmanya Tilak Municipal General Hospital, Mumbai. Two hundred and thirty-one patients with dyspepsia were randomized to a 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or to standard 14-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the triple therapy. Per-protocol eradication rate of sequential therapy was 92.4% (95% CI 85.8-96.1%) vs. 81.8% (95% CI 73.9-87.8%) (p = 0.027) for standard drug therapy. Intention-to-treat eradication rates were 88.2% (95% CI 80.9-93.0%) vs. 79.1% (95% CI 71.1-85.4%), p = 0.029, respectively. The incidence of major and minor side effects between therapy groups was not significantly different (14.6% in the triple therapy group vs. 23.5% in sequential group, p = 0.12). Follow up was incomplete in 3.3% and 4.7% patients in standard and sequential therapy groups, respectively. Sequential therapy includes one additional antibiotic (tinidazole) that is not contained in standard therapy. Sequential therapy was significantly better than standard therapy for eradicating H. pylori infection.

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

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

PubMed

Finocchiaro, L M E; Glikin, G C

2012-12-01

We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0≤VCOG-CTCAE grade≤1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.

Effectiveness of massage therapy as co-adjuvant treatment to exercise in osteoarthritis of the knee: a randomized control trial.

PubMed

Cortés Godoy, Virginia; Gallego Izquierdo, Tomás; Lázaro Navas, Irene; Pecos Martín, Daniel

2014-01-01

The effectiveness of exercise therapy in the treatment of osteoarthritis of the knee (KOA) is widely evidenced. The current study aims to compare the effectiveness of massage therapy as a co-adjuvant treatment for KOA. A blind, randomized controlled trial design was used. Eighteen women were randomly allocated to two different groups. Group A was treated with massage therapy and an exercise program, and Group B was treated with the exercise program alone. The intervention lasted for 6 weeks. Outcomes were assessed using a verbal analogue scale (VAS), the WOMAC index, and the Get-Up and Go test. Baseline, post-treatment, and 1- and 3- month follow-up data were collected. Values were considered statistically significant at a p < 0.05. The Mann-Whitney U test was applied in order to find out the differences between groups, and to verify the existence of such differences, the Friedman Test for repeated measures complemented with multiple comparisons tests was carried out. In both groups, significant differences were found in the three variables between the baseline measurement and three months after treatment, with the exception of the WOMAC variable in group B (p=0.064) No significant differences were found between both groups in the WOMAC index (p=0.508) and VAS (p=0.964) variables and the Get-Up and Go test (p=0.691). Combining exercise-based therapy with massage therapy may lead to clinical improvement in patients with KOA. The use of massage therapy combined with exercise as a treatment for gonarthrosis does not seem to have any beneficial effects.

Successful management of Churg-Strauss syndrome using omalizumab as adjuvant immunomodulatory therapy: first documented pediatric case.

PubMed

Iglesias, E; Camacho Lovillo, M; Delgado Pecellín, I; Lirola Cruz, M J; Falcón Neyra, M D; Salazar Quero, J C; Bernabeu-Wittel, J; González Valencia, J P; Neth, O

2014-03-01

Churg-Strauss syndrome (CSS) is an anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis; it is extremely rare in childhood and defined according to the Chapel-Hill Consensus as an eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels. Children commonly have a history of asthma and sinusitis whilst clinical presentation typically involves pulmonary tract and less frequently skin, heart, gastrointestinal tract, and peripheral nerves. Cardiopulmonary disease is higher in children and prognosis is worse. It is associated with significant eosinophilia and raised serum IgE-levels. ANCA are only found in 25% of childhood cases. Here we report the case of a 10-year-old girl who presented to us with vomiting, abdominal pain, and weight loss, paresthesias of lower extremities and breathlessness as well as a history of asthma, sinusitis and allergic rhinitis. She was treated with corticosteroids, cyclophosphamide, intravenous immunoglobulin, mycophenolate mofetil (MMF), and rituximab. However, remission was only achieved after initiation of omalizumab therapy, a recombinant humanized anti-IgE antibody. To the best of our knowledge this is the first pediatric patient suffering from CSS successfully managed with adjuvant anti-IgE therapy resulting in the control of respiratory as well as gastrointestinal symptoms. © 2013 Wiley Periodicals, Inc.

Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

PubMed

Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

2018-01-01

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer.

PubMed

Ribi, K; Aldridge, J; Phillips, K-A; Thompson, A; Harvey, V; Thürlimann, B; Cardoso, F; Pagani, O; Coates, A S; Goldhirsch, A; Price, K N; Gelber, R D; Bernhard, J

2012-05-08

In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

PubMed

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced

An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

PubMed Central

Stark, Felicity C.; Weeratna, Risini D.; Deschatelets, Lise; Gurnani, Komal; Dudani, Renu; Krishnan, Lakshmi

2017-01-01

Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA) melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1) compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18), significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies. PMID:29072624

Novel high throughput pooled shRNA screening identifies NQO1 as a potential drug target for host directed therapy for tuberculosis

PubMed Central

Li, Qing; Karim, Ahmad F.; Ding, Xuedong; Das, Biswajit; Dobrowolski, Curtis; Gibson, Richard M.; Quiñones-Mateu, Miguel E.; Karn, Jonathan; Rojas, Roxana E.

2016-01-01

Chemical regulation of macrophage function is one key strategy for developing host-directed adjuvant therapies for tuberculosis (TB). A critical step to develop these therapies is the identification and characterization of specific macrophage molecules and pathways with a high potential to serve as drug targets. Using a barcoded lentivirus-based pooled short-hairpin RNA (shRNA) library combined with next generation sequencing, we identified 205 silenced host genes highly enriched in mycobacteria-resistant macrophages. Twenty-one of these “hits” belonged to the oxidoreductase functional category. NAD(P)H:quinone oxidoreductase 1 (NQO1) was the top oxidoreductase “hit”. NQO1 expression was increased after mycobacterial infection, and NQO1 knockdown increased macrophage differentiation, NF-κB activation, and the secretion of pro-inflammatory cytokines TNF-α and IL-1β in response to infection. This suggests that mycobacteria hijacks NQO1 to down-regulate pro-inflammatory and anti-bacterial functions. The competitive inhibitor of NQO1 dicoumarol synergized with rifampin to promote intracellular killing of mycobacteria. Thus, NQO1 is a new host target in mycobacterial infection that could potentially be exploited to increase antibiotic efficacy in vivo. Our findings also suggest that pooled shRNA libraries could be valuable tools for genome-wide screening in the search for novel druggable host targets for adjunctive TB therapies. PMID:27297123

Drug Therapy for Stable Angina Pectoris.

PubMed

Rousan, Talla A; Mathew, Sunil T; Thadani, Udho

2017-03-01

Chronic stable angina pectoris refers to the predictable, reproducible occurrence of pressure or a choking sensation in the chest or adjacent areas caused by myocardial ischemia in association with physical or emotional stress, and cessation of exertion and or sublingual nitroglycerin invariably relieves the discomfort. It is a common presenting symptom of severe narrowing of one or more coronary arteries, non-obstructive coronary arteries, or even when the coronary arteries are angiographically normal. Patients often avoid activities which precipitate symptoms and have impaired quality of life. Most patients with angina pectoris can be managed with lifestyle changes, especially abstinence from smoking and regular exercise, and anti-anginal drugs. However, the choice of initial or combination antianginals as recommended in the guidelines is not evidence based. In addition, patients with stable angina due to coronary artery disease should also receive aspirin and a statin. Treatment of patients with angina and normal coronary arteries remains to be established. The aim of this article is to provide the readers not only with a guideline-based approach, which varies from one country to another, but also an individual-based approach, which takes into consideration circulatory status and the presence or absence of comorbidities in the treatment decision-making process. This manuscript primarily deals with drug therapy of stable angina pectoris and not coronary artery revascularization, which also provides angina relief but is usually reserved for patients who fail to respond to adequate drug therapy.

Microsponges based novel drug delivery system for augmented arthritis therapy.

PubMed

Osmani, Riyaz Ali M; Aloorkar, Nagesh H; Ingale, Dipti J; Kulkarni, Parthasarathi K; Hani, Umme; Bhosale, Rohit R; Jayachandra Dev, Dandasi

2015-10-01

The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug-polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 μm mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug-polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders.

Acute drug prescribing to children on chronic antiepilepsy therapy and the potential for adverse drug interactions in primary care

PubMed Central

Novak, Philipp H; Ekins-Daukes, Suzie; Simpson, Colin R; Milne, Robert M; Helms, Peter; McLay, James S

2005-01-01

Aims To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug–drug interactions. Design Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0–17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. Setting One hundred and sixty-one general practices throughout Scotland. Results During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non-epileptic drug therapy were eight, 11, six, and six for the 0–1, 2–4, 5–11, and 12–17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age-adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0–1, 2–4, 5–11, and 12–17-year-old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning. Conclusions In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could

Leptin-based adjuvants: an innovative approach to improve vaccine response.

PubMed

White, Sarah J; Taylor, Matthew J; Hurt, Ryan T; Jensen, Michael D; Poland, Gregory A

2013-03-25

Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥30 kg/m(2)) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin's role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Leptin-based Adjuvants: An Innovative Approach to Improve Vaccine Response

PubMed Central

White, Sarah J.; Taylor, Matthew J.; Hurt, Ryan; Jensen, Michael D.; Poland, Gregory A.

2013-01-01

Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥ 30 kg/m2) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin’s role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants. PMID:23370154

The application of machine learning techniques in the clinical drug therapy.

PubMed

Meng, Huan-Yu; Jin, Wan-Lin; Yan, Cheng-Kai; Yang, Huan

2018-05-25

The development of a novel drug is an extremely complicated process that includes the target identification, design and manufacture, and proper therapy of the novel drug, as well as drug dose selection, drug efficacy evaluation, and adverse drug reaction control. Due to the limited resources, high costs, long duration, and low hit-to-lead ratio in the development of pharmacogenetics and computer technology, machine learning techniques have assisted novel drug development and have gradually received more attention by researchers. According to current research, machine learning techniques are widely applied in the process of the discovery of new drugs and novel drug targets, the decision surrounding proper therapy and drug dose, and the prediction of drug efficacy and adverse drug reactions. In this article, we discussed the history, workflow, and advantages and disadvantages of machine learning techniques in the processes mentioned above. Although the advantages of machine learning techniques are fairly obvious, the application of machine learning techniques is currently limited. With further research, the application of machine techniques in drug development could be much more widespread and could potentially be one of the major methods used in drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug therapy problems and medication discrepancies during care transitions in super-utilizers.

PubMed

Surbhi, Satya; Munshi, Kiraat D; Bell, Paula C; Bailey, James E

First, to investigate the prevalence and types of drug therapy problems and medication discrepancies among super-utilizers, and associated patient characteristics. Second, to examine the outcomes of pharmacist recommendations and estimated cost avoidance through care transitions support focused on medication management. Retrospective analysis of the pharmacist-led interventions as part of the SafeMed Program. A large nonprofit health care system serving the major medically underserved areas in Memphis, Tennessee. Three hundred seventy-four super-utilizing SafeMed participants with multiple chronic conditions and polypharmacy. Comprehensive medication review, medication therapy management, enhanced discharge planning, home visits, telephone follow-up, postdischarge medication reconciliation, and care coordination with physicians. Types of drug therapy problems, outcomes of pharmacist recommendations, estimated cost avoided, medication discrepancies, and self-reported medication adherence. Prevalence of drug therapy problems and postdischarge medication discrepancies was 80.7% and 75.4%, respectively. The most frequently occurring drug therapy problems were enrollee not receiving needed medications (33.4%), underuse of medications (16.9%), and insufficient dose or duration (11.2%). Overall 50.8% of the pharmacist recommendations were accepted by physicians and patients, resulting in an estimated cost avoidance of $293.30 per drug therapy problem identified. Multivariate analysis indicated that participants with a higher number of comorbidities were more likely to have medication discrepancies (odds ratio 1.23 [95% CI 1.05-1.44]). Additional contributors to postdischarge medication discrepancies were difficulty picking up and paying for medications and not being given necessary prescriptions before discharge. Drug therapy problems and medication discrepancies are common in super-utilizers with multiple chronic conditions and polypharmacy during transitions of care

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

PubMed

Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

2009-02-01

Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

PubMed

Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

2008-09-01

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

Experimental study on oral sulfhydryl as an adjuvant for improving nitrate ester tolerance in an animal model.

PubMed

Chen, L; Jiang, J-Q; Zhang, Y; Feng, H

2018-03-01

As an initial step in exploring the feasibility of oral sulfhydryl as an adjuvant for improving nitrate ester tolerance, this study was designed to experimentally test the adjuvant therapy in a rabbit model of atherosclerosis (AS). New Zealand white rabbits with induced AS were randomly divided into four groups: AS group, AS + nitrate ester group, AS + nitrate ester tolerance group, and AS + drug combination group. Additionally, four equivalent groups with healthy New Zealand white rabbits without AS were also conformed. After feeding the animals for 5 days, the concentrations of superoxide anion (•O2-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) in blood and the relaxation response of the aortic ring were determined in each subject. The vascular plaques in different treatment groups were assessed by Hematoxylin and eosin (HE) staining to investigate the therapeutic value of sulfhydryl as coadjuvant for improving nitrate ester tolerance, and changes in blood vessels in different treatment groups were studied by immunohistochemical assays. Our results showed no significant differences through time in the concentrations of •O2-, SOD, MDA, NO, ET-1 between the healthy control and the nitrate ester groups (p > 0.05). The levels of SOD and MDA in the nitrate ester tolerance group increased with time, however, the levels of •O2-, NO and ET-1 decreased gradually (p < 0.05). The NO, •O2- and ET-1 levels in both the AS and AS + nitrate ester tolerance groups were significantly decreased, but SOD and MDA were significantly increased (p < 0.05). SOD and MDA in the AS + nitrate ester group decreased gradually with time, but •O2-, NO- and ET-1 levels increased (p < 0.05). The levels of SOD and MDA in the AS + drug combination and the drug combination group decreased significantly with time, in contrast, those of •O2-, NO- and ET-1 increased (p < 0.05). The results of HE staining proved that the atherosclerosis model

A pan-inhibitor of DASH family enzymes induces immune-mediated regression of murine sarcoma and is a potent adjuvant to dendritic cell vaccination and adoptive T-cell therapy.

PubMed

Duncan, Brynn B; Highfill, Steven L; Qin, Haiying; Bouchkouj, Najat; Larabee, Shannon; Zhao, Peng; Woznica, Iwona; Liu, Yuxin; Li, Youhua; Wu, Wengen; Lai, Jack H; Jones, Barry; Mackall, Crystal L; Bachovchin, William W; Fry, Terry J

2013-10-01

Multimodality therapy consisting of surgery, chemotherapy, and radiation will fail in approximately 40% of patients with pediatric sarcomas and result in substantial long-term morbidity in those who are cured. Immunotherapeutic regimens for the treatment of solid tumors typically generate antigen-specific responses too weak to overcome considerable tumor burden and tumor suppressive mechanisms and are in need of adjuvant assistance. Previous work suggests that inhibitors of DASH (dipeptidyl peptidase IV activity and/or structural homologs) enzymes can mediate tumor regression by immune-mediated mechanisms. Herein, we demonstrate that the DASH inhibitor, ARI-4175, can induce regression and eradication of well-established solid tumors, both as a single agent and as an adjuvant to a dendritic cell (DC) vaccine and adoptive cell therapy (ACT) in mice implanted with the M3-9-M rhabdomyosarcoma cell line. Treatment with effective doses of ARI-4175 correlated with recruitment of myeloid (CD11b) cells, particularly myeloid DCs, to secondary lymphoid tissues and with reduced frequency of intratumoral monocytic (CD11bLy6-CLy6-G) myeloid-derived suppressor cells. In immunocompetent mice, combining ARI-4175 with a DC vaccine or ACT with tumor-primed T cells produced significant improvements in tumor responses against well-established M3-9-M tumors. In M3-9-M-bearing immunodeficient (Rag1) mice, ACT combined with ARI-4175 produced greater tumor responses and significantly improved survival compared with either treatment alone. These studies warrant the clinical investigation of ARI-4175 for treatment of sarcomas and other malignancies, particularly as an adjuvant to tumor vaccines and ACT.

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.

New drug candidates and therapeutic targets for tuberculosis therapy.

PubMed

Zhang, Ying; Post-Martens, Katrin; Denkin, Steven

2006-01-01

Despite advances in chemotherapy and the BCG (Bacillus Calmette-Guérin) vaccine, tuberculosis remains a significant infectious disease. Although it can be cured, the therapy takes at least 6-9 months, and the laborious and lengthy treatment brings with it dangers of noncompliance, significant toxicity and drug resistance. The increasing emergence of drug resistance and the problem of mycobacterial persistence highlight the need to develop novel TB drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria and shorten the length of treatment. Recent new and exciting developments in tuberculosis drug discovery show good promise of a possible revolution in the chemotherapy of tuberculosis.

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

PubMed

Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

2017-09-01

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.

PubMed

Weber, Jeffrey; Mandala, Mario; Del Vecchio, Michele; Gogas, Helen J; Arance, Ana M; Cowey, C Lance; Dalle, Stéphane; Schenker, Michael; Chiarion-Sileni, Vanna; Marquez-Rodas, Ivan; Grob, Jean-Jacques; Butler, Marcus O; Middleton, Mark R; Maio, Michele; Atkinson, Victoria; Queirolo, Paola; Gonzalez, Rene; Kudchadkar, Ragini R; Smylie, Michael; Meyer, Nicolas; Mortier, Laurent; Atkins, Michael B; Long, Georgina V; Bhatia, Shailender; Lebbé, Celeste; Rutkowski, Piotr; Yokota, Kenji; Yamazaki, Naoya; Kim, Tae M; de Pril, Veerle; Sabater, Javier; Qureshi, Anila; Larkin, James; Ascierto, Paolo A

2017-11-09

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population. At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

PubMed

Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

2017-07-01

The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update

PubMed Central

Krop, Ian; Ismaila, Nofisat; Andre, Fabrice; Bast, Robert C.; Barlow, William; Collyar, Deborah E.; Hammond, M. Elizabeth; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Wolff, Antonio C.; Stearns, Vered

2018-01-01

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations

Evaluation of Widely Consumed Botanicals as Immunological Adjuvants

PubMed Central

Ragupathi, Govind; Hood, Chandra; Yeung, K. Simon; Vickers, Andrew; Hood, Chandra; Deng, Gary; Cheung, Nai-Kong; Vickers, Andrew; Cassileth, Barrie; Livingston, Philip

2008-01-01

Background Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with 7 botanicals purported to have immune stimulant effects. Methods Groups of 5–10 mice were immunized with globo H–KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. 3 times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus vesicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast β-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semi-synthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH. Results Consistent significant adjuvant activity was observed after s.c vaccination with the Coriolus extracts (especially PSK

Targeted drug delivery for cancer therapy: the other side of antibodies

PubMed Central

2012-01-01

Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients. PMID:23140144

Phase I Trial of Aflibercept (VEGF Trap) with Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients with High-Grade Gliomas

PubMed Central

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred WK; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-01-01

Background Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG) with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Results Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4mg/kg every 2 weeks. Dose limiting toxicities (DLTs) at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. Conclusions This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4mg/kg every 2 weeks. PMID:28116649

Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

PubMed

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-03-01

Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

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

Agbahiwe, Harold C.; Wharam, Moody; Batra, Sachin

2013-02-01

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves andmore » descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.« less

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

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 treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

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

Outcomes of curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma of long bone.

PubMed

Kim, Wanlim; Han, Ilkyu; Kim, Eo Jin; Kang, Seungcheol; Kim, Han-Soo

2015-06-01

Low-grade chondrosarcoma of long bones can be treated successfully with extended intralesional curettage using adjuvants. However, there is no study reporting the use of anhydrous alcohol as an adjuvant in the treatment of low-grade chondrosarcoma. We asked (1) whether intralesional curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma is associated with good oncologic outcomes; and we report (2) the complications of the procedure. Thirty-six patients (13 men, 23 women) with a mean age of 46 years (range, 18-67 years) were treated for low-grade chondrosarcoma and followed up for a median of 62 months (range, 24-169 months). After intralesional curettage, and additional burring, anhydrous alcohol was used as an adjuvant therapy. At the time of last follow-up, there were no local recurrences or distant metastases. Six patients developed complications: 4 postoperative fractures (11%), 1 intra-articular loose body (3%) and 1 postoperative joint stiffness (3%). Anhydrous alcohol is a reasonable adjuvant for the curettage of low-grade chondrosarcoma of long bones. A long-term follow-up study is necessary, considering the slow biological progression of low-grade chondrosarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study.

PubMed

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B; Barwal, Anil

2014-12-01

CytoSorb(®) (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb(®) in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb(®) hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

PubMed Central

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B.; Barwal, Anil

2014-01-01

CytoSorb® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock. PMID:25538418

Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends.

PubMed

Badiee, Ali; Heravi Shargh, Vahid; Khamesipour, Ali; Jaafari, Mahmoud Reza

2013-01-21

Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study

PubMed Central

Figer, Arie; Nissan, Aviram; Shani, Adi; Borovick, Riva; Stiener, Mariana; Baras, Mario; Freund, Herbert R.; Sulkes, Aaron; Stojadinovic, Alexander; Peretz, Tamar

2011-01-01

Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV). Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months. Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival. Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset. PMID:21475636

Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

PubMed

González-Bello, Concepción

2017-09-15

Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Selected adjuvants as carriers of a dry extract of common ivy (Hedera helix L.)].

PubMed

Marczyński, Zbigniew; Zgoda, Marian Mikołaj; Bodek, Kazimiera Henryka

2011-01-01

The usefulness was tested of selected adjuvants: Vivapur 112, Carmellose calcium, Calcium carbonate CA 740, Calcium carbonate CA 800, Hypromellose as carriers of a dry extract of common ivy (Hedera helix L.) leaves in the process of direct tableting. The quality of the produced tablets was determined by examining their appearance, diameter, thickness, mass resistance to abrasion, crushing and disintegration time. Furthermore, the rate of release of biologically active components from the produced drug form to acceptor fluid was tested in accordance with the requirements of Polish Pharmacopoeia VII (PPVII). An attempt was made to estimate the effect of the used adjuvants on the course of this process. The applied adjuvants and acceptor fluid osmolarity decide significantly about the pharmaceutical availability of the therapeutic agents contained in the extract. The obtained model tablets are characterized by controlled release of biologically active substances, in majority of batches they fulfil the requirements as regards physicochemical properties. The formulation composition of the first batch (Extr. Hederae helices e fol.spir. sicc., Vivapur 112, Carmellose calcium, Sodium Stearyl Fumarate) appeared to be the most effective. The worked out method is optimal and provides technological reproducibility and high durability of the drug form.

Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

PubMed Central

Cortesi, Annalisa; Galuppi, Andrea; Arcelli, Alessandra; Romani, Fabrizio; Mattiucci, Gian Carlo; Bianchi, Giuseppe; Ferrari, Stefano; Ferraro, Andrea; Farioli, Andrea; Gambarotti, Marco; Righi, Alberto; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Buwenge, Milly; Valentini, Vincenzo; Morganti, Alessio Giuseppe; Donati, Davide; Cammelli, Silvia

2017-01-01

Purpose The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC. PMID:28725250