Showing papers by "Fabio A.B. Schutz published in 2011"
TL;DR: A systematic review and meta-analysis of randomized trials to determine whether androgen deprivation therapy (ADT) is associated with cardiovascular mortality, prostate cancer-specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer was performed in this article.
Abstract: Context Whether androgen deprivation therapy (ADT) causes excess cardiovascular deaths in men with prostate cancer is highly controversial and was the subject of a joint statement by multiple medical societies and a US Food and Drug Administration safety warning. Objective To perform a systematic review and meta-analysis of randomized trials to determine whether ADT is associated with cardiovascular mortality, prostate cancer–specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer. Data Sources A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials in English between January 1, 1966, and April 11, 2011. Study Selection Inclusion required nonmetastatic disease, intervention group with gonadotropin-releasing hormone agonist–based ADT, control group with no immediate ADT, complete information on cardiovascular deaths, and median follow-up of more than 1 year. Data Extraction Extraction was by 2 independent reviewers. Summary incidence, relative risk (RR), and CIs were calculated using random-effects or fixed-effects models. Results Among 4141 patients from 8 randomized trials, cardiovascular death in patients receiving ADT vs control was not significantly different (255/2200 vs 252/1941 events; incidence, 11.0%; 95% CI, 8.3%-14.5%; vs 11.2%; 95% CI, 8.3%-15.0%; RR, 0.93; 95% CI, 0.79-1.10; P = .41). ADT was not associated with excess cardiovascular death in trials of at least 3 years (long duration) of ADT (11.5%; 95% CI, 8.1%-16.0%; vs 11.5%; 95% CI, 7.5%-17.3%; RR, 0.91; 95% CI, 0.75-1.10; P = .34) or in trials of 6 months or less (short duration) of ADT (10.5%; 95% CI, 6.3%-17.0%; vs 10.3%; 95% CI, 8.2%-13.0%; RR, 1.00; 95% CI, 0.73-1.37; P = .99). Among 4805 patients from 11 trials with overall death data, ADT was associated with lower PCSM (443/2527 vs 552/2278 events; 13.5%; 95% CI, 8.8%-20.3%; vs 22.1%; 95% CI, 15.1%-31.1%; RR, 0.69; 95% CI, 0.56-0.84; P Conclusion In a pooled analysis of randomized trials in unfavorable-risk prostate cancer, ADT use was not associated with an increased risk of cardiovascular death but was associated with a lower risk of PCSM and all-cause mortality.
404 citations
TL;DR: This is the first comprehensive report to show that bevacizumab is associated with an increased risk of significant heart failure in patients with breast cancer.
Abstract: Purpose Bevacizumab is a treatment option in patients with metastatic breast cancer. Congestive heart failure (CHF) has been reported, although the overall incidence and relative risk (RR) of this complication remains unclear. We performed an up-to-date, comprehensive meta-analysis to determine the risk of serious CHF in patients with breast cancer receiving bevacizumab.
260 citations
TL;DR: Sunitinib use is associated with increased risk of CHF in patients with cancer and there was no difference observed in CHF incidence for patients with RCC versus non-RCC or in trials with or without cardiac monitoring.
Abstract: Purpose Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma (RCC) and GI stromal tumor. Congestive heart failure (CHF) is an important adverse effect that has been reported with sunitinib, but overall incidence and relative risk (RR) remain undefined. We performed an up-to-date meta-analysis to determine the risk of developing CHF in patients with both RCC and non-RCC tumors treated with sunitinib. Methods Medline databases were searched for articles published between January 1966 and February 2011. Eligible studies were limited to phase II and III trials of sunitinib with adequate safety reporting in patients with cancer of any tumor type. Summary incidence, RR, and 95% CIs were calculated using random- or fixed-effects models based on the heterogeneity of included studies. Results A total of 6,935 patients were included. Overall incidence for all- and high-grade CHF in sunitinib-treated patients was 4.1% (95% CI, 1.5% to 10.6%) and 1.5% (95% CI,...
156 citations
TL;DR: A meta-analysis of randomized controlled trials to fully characterize the arterial thromboembolic events (ATEs) risk with bevacizumab in certain patients' subgroups found that treatment is associated with a significant increase in the risk of arterialThrombosis.
143 citations
TL;DR: Pazopanib showed clinical activity in several tumors including renal cell cancer, breast cancer, soft tissue sarcoma, thyroid cancer, hepatocellular cancer and cervical cancer, and was well tolerated with the main side effects being hypertension, fatigue and gastrointestinal disorders.
Abstract: Pazopanib is an oral, multi-targeted, tyrosine kinase inhibitor (TKI) that binds to the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and several other key proteins responsible for angiogenesis, tumor growth and cell survival. Pazopanib exhibited in vivo and in vitro activity against tumor growth and, in early clinical trials, was well tolerated with the main side effects being hypertension, fatigue and gastrointestinal disorders. Pazopanib showed clinical activity in several tumors including renal cell cancer (RCC), breast cancer, soft tissue sarcoma, thyroid cancer, hepatocellular cancer and cervical cancer. A phase III clinical trial in metastatic RCC patients showed a significant improvement in progression-free survival, leading to its approval in the US. In metastatic breast cancer, the combination of pazopanib with lapatinib was more effective than lapatinib alone. At the time of the current publication, pazopanib is being evaluated in more than 35 phase II and III trials.
136 citations
TL;DR: In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.
113 citations
TL;DR: TA use for stage I RCC increased over a relatively short period and was performed more commonly in patients of older age and with smaller tumor size, and no statistical difference in cancer-specific or overall survival between TA vs PN or RN was found.
93 citations
TL;DR: Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia.
Abstract: Background Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent, hematological toxicities have been reported with this drug but the incidence and risk have not been formerly assessed. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with sorafenib use. Methods The databases of Medline were searched for articles from 1966 to May 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with sorafenib, and adequate safety data profile reporting anemia, neutropenia, lymphopenia or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI). Results A total of 3221 patients were included. The incidences of sorafenib-associated all-grade anemia, neutropenia, thrombocytopenia and lymphopenia were 43.9%, 18.0%, 25.3% and 34.1%, respectively. The incidences of high-grade events were 2.0%, 5.1%, 4.0% and 13.1%, respectively. Sorafenib was associated with a decreased risk of high-grade anemia (RR = 0.62; 95% CI, 0.39–0.98), an increased risk of all-grade (RR = 1.69; 95% CI, 1.33–2.17) and high-grade (RR = 1.61; 95% CI, 1.02–2.57) neutropenia, all-grade (RR = 2.56; 95% CI, 1.37–4.80) and high-grade (RR = 3.63; 95% CI, 1.98–6.66) thrombocytopenia, and high-grade lymphopenia (RR = 1.84; 95% CI, 1.22–2.78). Stratified analysis by the presence or not of concomitant chemotherapy demonstrated similar risks. Conclusions Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia.
53 citations
TL;DR: Bvacizumab is associated with a lower risk of anaemia and increased risks of neutropenia, thrombocytopenia and febrile neutropania, a meta-analysis performed to determine the incidence and risk of haematologic toxicities associated with bevacIZumab.
38 citations
TL;DR: Vinflunine is currently approved in Europe for the treatment of second-line TCCU and is currently being developed in other malignancies, where it has been shown to have predictable and manageable adverse effects, such as neutropenia, anemia, constipation and fatigue.
Abstract: Introduction: Vinca alkaloid agents have been widely used in several different types of malignancies However, cancer cells, ultimately, develop resistance to these agents Therefore, the development of new agents with improved efficacy is warranted Recently, a new synthetic vinca alkaloid, vinflunine, was developed through the addition of two fluor molecules by superacidic chemistry Areas covered: The authors describe the development of the new vinca alkaloid vinflunine from preclinical studies to the late-stage clinical trials, highlighting the most important clinical and safety data of vinflunine In vitro and in vivo studies have shown a superior efficacy of vinflunine over other vinca alkaloids and with an improved safety profile Early clinical trials have demonstrated a significant activity of vinflunine against different malignancies Phase III trials showed that vinflunine increases survival in patients with advanced transitional cell carcinoma of the urothelium (TCCU) tract treated in the seco
37 citations
TL;DR: These two trials provide several key concepts and definitions that need to be considered when designing new trials and interpreting results in the second-line setting, and a strict definition of what is ‘second line’ is needed.
TL;DR: Preliminary data suggest that pneumonitis maybe a marker of therapeutic benefit in patients given mTOR inhibitor treatment and is seen in up to one third of pts.
Abstract: e15176 Background: mTOR inhibitors have been recently approved for use in patients with metastatic renal cell carcinoma (mRCC) and are under intense investigation in several other malignancies. We ...
TL;DR: Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia.
Abstract: 352 Background: Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent...
TL;DR: This is the first large multi-institutional report to show that low serum sodium is independently associated with a worse outcome in mRCC pts treated with VEGF-targeted agents.
Abstract: 322 Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients (pts) treated with immunotherapy (Jeppesen et al, Br J Cancer. 2010). We sought to investigate the influence of baseline hyponatremia in mRCC pts treated with contemporary vascular endothelial growth factor (VEGF)- targeted therapy in a larger international and multi-institutional database. Methods: Baseline characteristics and outcomes on 855 pts treated with first-line anti-VEGF therapy for mRCC were available from 8 Cancer Centers to study the impact of hyponatremia (defined as serum Na<135 mmol/L) on clinical outcome as measured by overall survival (OS), time to treatment failure (TTF), best response (CR, PR, SD and PD). Results: Median OS after treatment initiation was 16.8 months (mos) (95% CI: 14.9, 18.5 mos), with 334 (39%) of patients remaining alive. Median follow-up in pts alive was 18.8 mos. Med...
TL;DR: Genomic gain of a short segment of chromosome 1q23.3 is associated with a lethal phenotype of UC in patients with metastatic disease in a cohort of 94 UC patients uniformly-treated for distant metastases.
Abstract: 4569 Background: Limited information exists regarding the changes that occur in UC tumors that ultimately metastasize, the lethal phenotype of UC. Recurrent copy number alterations (CNAs) have been...
TL;DR: Conurrent use of bevacizumab with chemotherapy or immunotherapy is associated with a lower risk of high-grade anemia and an increased risk ofhigh-grade neutropenia and febrile neutropania.
Abstract: 336 Background: Bevacizumab is a humanized monoclonal antibody directed against the VEGF ligand. Clinical trials with this drug mainly included patients with renal cell cancer (in combination with interferon-alpha) and several other solid tumors (in combination with cytotoxic chemotherapy). Although hematologic toxicities are not among the main concerns associated with the addition of bevacizumab, discontinuation of therapy or dose reductions due to these toxicities have been reported. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with bevacizumab use. Methods: The databases of Medline were searched for articles from 1966 to September 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with bevacizumab, and adequate safety data profile reporting anemia, neutropenia, febrile neutropenia, or thrombocytopenia. Statistical analyses were conducted to calculate the s...
TL;DR: This is the first study to implicate germline variations in critical signaling pathways with cancer recurrence in patients with localized RCC, and three SNPs in 2 genes were found to be highly predictive of RFI in univariate analysis.
Abstract: 4506 Background: Gene polymorphisms in critical signaling pathways may impact recurrence in patients with localized renal cell cancer (RCC) Methods: Germline DNA was extracted from 425 patients of European-American ancestry that were enrolled in a prospective protocol with full baseline and follow up clinical data. Using the Sequenom iPLEX Gold platform, genotyping was performed for select genes involved in RCC pathogenesis, angiogenesis, metabolism, and immune regulation, including VHL, HIF-1, HIF-2, VEGF, VEGFR-2, CAIX, mTOR, PI3K, CTLA4, PD1, and B7H1. The primary endpoint was recurrence free interval (RFI), defined as time from surgery to recurrence or last follow-up. Cox Proportional Hazards model was used to evaluate and identify single nucleotide polymorphisms (SNPs) associated with RFI. A multivariate model adjusted for clinical factors which predict recurrence. The false discovery rate (pFDR) was used to control for the number of tests performed. With 45% RFI events, and 10% variant prevalence, t...
TL;DR: This is the first comprehensive report to demonstrate that sunitinib use is associated with an increased risk of significant heart failure in cancer patients.
Abstract: 316 Background: Sunitinib is a multitargeted receptor tyrosine kinase inhibitor that is widely used in the treatment of renal cell cancer (RCC) and several other malignancies. Congestive heart fail...
TL;DR: A reduction of 10% in the SLD on the first follow-up imaging study is a better early predictor of disease outcome than response criteria using RECIST in patients with advanced TCCU receiving second-line VFL therapy.
Abstract: 4570 Background: Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) in patients who progress a...