Stony Brook, NY, United States
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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.

Chen C.,Shanghai University | Xu T.,Shanghai University | Chen J.,Shanghai University | Zhou J.,Shanghai University | And 3 more authors.
European Journal of Neurology | Year: 2011

We evaluated the association between allergic conditions and the risk of glioma in case-control and cohort studies published so far on this issue. A total of 12 studies (10 case-control and 2 cohort studies) were included in the analysis, involving 61 090 participants, of whom 6408 had glioma. When compared with non-allergic conditions, the pooled odds ratio (OR) with any allergic conditions for glioma was 0.60 (95% CI: 0.52-0.69, P<0.001), suggesting a significant negative association (protective effect) between allergy and glioma. Subgroup analysis showed that the ORs were 0.70 (95% CI: 0.62-0.79, P<0.001), 0.69 (95% CI: 0.62-0.78, P<0.001), and 0.78 (95% CI: 0.70-0.87, P<0.001) for asthma, eczema, and hay fever, respectively. The significant association remained even after excluding the bias of proxy reporting (OR=0.61; 95% CI: 0.50-0.75, P<0.001). We conclude that allergic conditions may significantly reduce the risk of glioma. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

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.

Balagula Y.,Sloan Kettering Cancer Center | Wu S.,Stony Brook University Cancer Center | Su X.,Stony Brook University Cancer Center | Feldman D.R.,Sloan Kettering Cancer Center | Lacouture M.E.,Sloan Kettering Cancer Center
Investigational New Drugs | Year: 2012

Pazopanib is a novel multikinase inhibitor that shares a similar spectrum of target receptors with sorafenib and sunitinib. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib and compare the difference in incidence between sorafenib, sunitinib, and pazopanib. Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. A total of 1,163 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.8% (95% CI: 0.7-4.6%), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased for allgrade (RR=6.09, 95% CI: 1.11-33.36, p=0.037) and highgrade HFSR (RR=2.51, 95% CI: 0.12-51.9, p=0.55). The risk of all-grade and high-grade HFSR to pazopanib was significantly lower as compared to sorafenib and sunitinib (RR=7.5, 95% CI: 5.5-10.2, p<0.001; RR=5.9, 95% CI: 3.5-10.0, p<0.001 and RR=4.2, 95% CI: 3.0-5.7, p< 0.001; RR=3.6, 95% CI: 2.1-6.2, p<0.001). Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis. © Springer Science+Business Media, LLC 2011.

Wu S.,Stony Brook University Cancer Center | Keresztes R.S.,Stony Brook University Cancer Center
Cancer Investigation | Year: 2011

Novel agents to reduce angiogenesis by targeting vascular endothelial growth factor and other proangiogenic signaling pathways are being developed for advanced nonsmall cell lung cancer. Antibody-based therapies (e.g., aflibercept) and multitargeted tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, and BIBF 1120) are being evaluated in phase III clinical trials. Some antiangiogenic agents have demonstrated distinct profiles in producing a variety of nonhematologic toxicities, including bleeding/hemorrhage, venous and arterial thromboembolic events, gastrointestinal perforation, hypertension, and proteinuria. Elucidating the molecular basis of these toxicities may lead to clinical benefits by improving patient selection and allowing for the development of effective prevention and management strategies. © 2011 Informa Healthcare USA, Inc.

Sloan S.R.,Harvard University | Parker R.I.,Stony Brook University Cancer Center
Transfusion Medicine Reviews | Year: 2016

Outside the neonatal period, most platelets that are transfused to pediatric patients are given to those who are thrombocytopenic secondary to malignancy and associated therapy and/or hematopoietic progenitor cell transplant, or to those with significant bleeding associated with surgery, especially cardiac surgery. Indications for platelet transfusion, doses, and other practices for children largely mimic adult platelet transfusion protocols because there are few pediatric-specific studies in this area. Pediatric platelet transfusion practices would benefit from focused pediatric research. The appropriate indications and doses for platelet transfusions in oncology, hematopoietic progenitor cell transplant, and cardiac surgery patients need to be determined. © 2016.

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.

Balagula Y.,Sloan Kettering Cancer Center | Wu S.,Stony Brook University Cancer Center | Su X.,Stony Brook University Cancer Center | Lacouture M.E.,Sloan Kettering Cancer Center
Annals of Oncology | Year: 2011

Background: The effect of chemotherapy on the risk of cetuximab-induced acneiform rash is unknown. We carried out a systematic review and meta-analysis of published studies to quantify the incidence and risk of high-grade acneiform rash with combination therapy. Methods: Relevant studies were identified from PubMed database, abstracts presented at the American Society of Clinical Oncology conferences, and Web of Science. Incidence of acneiform rash to cetuximab monotherapy was estimated based on updated data from our previously published meta-analysis. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated based on the heterogeneity of included studies. Results: A total of 5333 patients from nine trials were included in the analysis. The incidence of high-grade acneiform rash was significantly increased in patients receiving combination treatment (12.8%, 95% CI 9.1% to 17.7%) as compared with cetuximab monotherapy (6.3%, 95% CI 3.7% to 10.5%), with a risk ratio of 2.03 (95% CI 1.52-2.71, P < 0.01). Cetuximab significantly increased the risk of high-grade rash in patients receiving combination therapy (RR = 37.7, 95% CI 17.8-80.0, P < 0.001). Conclusions: Addition of cytotoxic chemotherapy to cetuximab significantly increases the risk of high-grade acneiform rash compared with cetuximab monotherapy. This emphasizes the need for effective management strategies. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Kajimura D.,Columbia University | Lee H.W.,Columbia University | Riley K.J.,Columbia University | Arteaga-Solis E.,Columbia University | And 8 more authors.
Cell Metabolism | Year: 2013

The synthesis of adiponectin, an adipokine with ill-defined functions in animals fed a normal diet, is enhanced by the osteoblast-derived hormone osteocalcin. Here we show that adiponectin signals back in osteoblasts to hamper their proliferation and favor their apoptosis, altogether decreasing bone mass and circulating osteocalcin levels. Adiponectin fulfills these functions, independently of its known receptors and signaling pathways, by decreasing FoxO1 activity in a PI3-kinase-dependent manner. Over time, however, these local effects are masked because adiponectin signals in neurons of the locus coeruleus, also through FoxO1, to decrease the sympathetic tone, thereby increasing bone mass and decreasing energy expenditure. This study reveals that adiponectin has the unusual ability to regulate the same function in two opposite manners depending on where it acts and that it opposes, partially, leptin's influence on the sympathetic nervous system. It also proposes that adiponectin regulation of bone mass occurs through a PI3-kinase-FoxO1 pathway. © 2013 Elsevier Inc.

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