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Stony Brook, NY, United States

Bayliss T.J.,Dartmouth Hitchcock Medical Center | Smith J.T.,Alder Inc | Schuster M.,Stony Brook University Cancer Center | Dragnev K.H.,Dartmouth Hitchcock Medical Center | Rigas J.R.,Dartmouth Hitchcock Medical Center
Expert Opinion on Biological Therapy | Year: 2011

Inflammatory pathways may be an important contributor to morbidity and mortality associated with lung cancer. The oncogene-associated inflammatory microenvironment leads to production of inflammatory cytokines such as IL-6. IL-6 is associated with poor prognosis and correlates with debilitating lung-cancer-related symptoms such as fatigue, thromboembolism, cachexia and anemia. IL-6 has been implicated in resistance of lung cancer to EGF inhibitors. A mAb therapy targeting IL-6 may be an effective treatment for the inflammatory microenvironment in lung cancer. Areas covered: An understanding of the inflammatory pathways involved in lung cancer, including the central role of IL-6, and how inflammation affects the course and treatment of lung cancer. The mAb ALD518, which targets IL-6, and its investigational development and use in advanced NSCLC. Preclinical and Phase I and II studies of ALD518 with a focus on NSCLC. How ALD518 could be used in NSCLC in the future. Expert opinion: IL-6-mediated inflammation may contribute to NSCLC-related morbidity and mortality. In preclinical and Phase I and II trials ALD518 targeting IL-6 appears well tolerated and ameliorates NSCLC-related anemia and cachexia. Other clinical outcomes need further study, and may include effects on overall survival, hypercoagulability associated with lung cancer and decreased resistance to EGF-pathway inhibitors. © 2011 Informa UK, Ltd.

Chen T.,Shanghai University | Xu T.,Shanghai University | Li Y.,Shanghai University | Liang C.,Shanghai University | And 4 more authors.
Cancer Treatment Reviews | Year: 2011

Background: Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment. Methods: We searched PubMed and Web of Science (January 1966-July 2009) and American Society of Clinical Oncology conferences held (January 2000-July 2009) for relevant articles and abstracts. Summary incidence rates, relative risks (RRs), and 95% confident intervals (CIs) were calculated using a fixed-effects or random-effects model. Results: 11,882 patients from 10 RCTs were included for analysis. The incidences of LVEF decrease and congestive heart failure (CHF) were 7.5% (95% CI 4.2-13.1) and 1.9% (95% CI 1.0-3.8) among patients receiving trastuzumab. Trastuzumab significantly increased the risk of LVEF decrease (RR = 2.13, 95% CI, 1.31-3.49; p=0.003). In addition, it significantly increased the risk of CHF (RR=4.19, 95% CI 2.73-6.42; p< 0.00001). The increased risk of CHF was observed in patients with early stage (RR=4.05, 95% CI 2.49-6.58; p< 0.00001) as well as metastatic disease (RR=4.75, 95% CI 1.93-11.71; p=0.0007). Furthermore, trastuzumab significantly increased the risk of CHF (RR=4.27, 95% CI 2.75-6.61, p< 0.00001) in patients receiving anthracycline-based chemotherapy, but not in patients receiving non-anthracycline chemotherapy (RR=2.42, 95% CI 0.36-16.19, p=0.36). Conclusion: The addition of trastuzumab to anthracycline-based chemotherapy significantly increase the risk of cardiac dysfunction in breast cancer patients. Further studies are recommended for non-anthracycline chemotherapy. © 2010 Elsevier Ltd.

Saggar V.,New York University | Wu S.,Stony Brook University Cancer Center | Dickler M.N.,Sloan Kettering Cancer Center | Lacouture M.E.,Sloan Kettering Cancer Center
Oncologist | Year: 2013

Background. Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies. Methods. An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II-III studies using the terms "tamoxifen," "toremifene," "raloxifene," "anastrozole," "letrozole," "exemestane," "fulvestrant," "leuprolide," "flutamide," "bicalutamide," "nilutamide," "fluoxymesterone," "estradiol," "octreotide," "megestrol," "medroxyprogesterone acetate," "enzalutamide," and "abiraterone" were searched. Results. Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%-5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p <.001), with selective estrogen receptor modulators having the highest risk. Conclusion. Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients' quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event. © AlphaMed Press 2013.

Drucker A.M.,University of Toronto | Drucker A.M.,Sloan Kettering Cancer Center | Wu S.,Stony Brook University Cancer Center | Dang C.T.,Sloan Kettering Cancer Center | Lacouture M.E.,Sloan Kettering Cancer Center
Breast Cancer Research and Treatment | Year: 2012

Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Rash is inconsistently reported as a common adverse event in most clinical trials of pertuzumab, at varying incidences. In this study, we have investigated the overall incidence and risk of rash with pertuzumab. Relevant studies were identified from the PubMed database (1966-2012), abstracts presented at the American Society of Clinical Oncology annual conference (2004-2011), and Web of Science database (1998-2012). Eligible studies were prospective phase II-III clinical trials using pertuzumab in cancer patients. Incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using randomeffects or fixed-effects models based on the heterogeneity of included studies. Data from a total of 1,726 patients (pertuzumab, n = 1,157; controls, n = 569) with breast, ovarian, and prostate cancers from eight clinical trials were included for analysis. The incidence of all-grade and highgrade rash with pertuzumab were 24.6 % (95 % CI 19.3-30.8 %) and 1.1 % (95 % CI 0.5-2.2 %), respectively. The risk varied with tumor types, as patients with prostate cancer had a lower incidence of rash (13.2 %; 95 % CI 8.0-21.1 %) than those with breast, ovarian, fallopian tube, and peritoneal cancer (P = 0.001). Overall, pertuzumab significantly increased the risk of rash in comparison with controls (RR 1.53; 95 % CI 1.12-2.09; P = 0.007). Pertuzumab is associated with a significant risk of rash, and the incidence varies among different tumor types. Prevention, early recognition, and appropriate treatment of this rash may lead to improvement in patient quality of life, adherence to therapy, and possibly optimize clinical outcomes. © Springer Science+Business Media, LLC. 2012.

Drucker A.M.,University of Toronto | Drucker A.M.,Sloan Kettering Cancer Center | Wu S.,Stony Brook University Cancer Center | Busam K.J.,Sloan Kettering Cancer Center | And 3 more authors.
European Journal of Haematology | Year: 2013

Objectives: Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors approved for the treatment of chronic myeloid leukemia (CML). In clinical trials, they have both been reported to cause rash in a significant number of patients, but its incidence varies significantly and has not been characterized clinically or histologically. The aim of this study was to determine the incidence of rash with nilotinib and dasatinib, and to provide a clinical and histopathological description of the rash. Methods: We conducted a meta-analysis of clinical trials evaluating nilotinib and dasatinib to determine and compare the incidence of rash with these medications. Additionally, we performed a retrospective chart review to analyze the clinical presentation and histology of patients presenting with rash. Results: The incidence of all-grade (grade 1-4) rash with nilotinib was 34.3% (95% CI, 27.9-41.3), higher (P = 0.017) than with dasatinib (23.3%; 95% CI, 18.8-28.6). Similarly, the incidence of high-grade rash with nilotinib (2.6%; 95% CI, 2.1-3.4) was higher (P = 0.002) than with dasatinib (1.1%; 95% CI, 0.8-1.6). The clinical presentation often consisted of a pruritic, perifollicular hyperkeratotic, occasionally erythematous papular rash affecting most areas of the body, depending on the severity. Conclusions: Both nilotinib and dasatinib are associated with rash in a significant number of patients. Further studies to prevent and treat rash with nilotinib and dasatinib are required to improve patient quality of life, adherence with therapy and oncologic outcome. © 2012 John Wiley & Sons A/S.

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