Management of bladder cancer: current and emerging strategies.
ABSTRACT Cancer of the urinary bladder is the fifth most prevalent solid tumour in the US. Urothelial carcinoma is the most common form of bladder cancer, accounting for about 90% of cases. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. Urothelial carcinoma is a chemo-sensitive disease, with a high overall and complete response rate to combination chemotherapy. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. The role of adjuvant chemotherapy in this setting is yet to be validated. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients. Currently, there is no standard second-line therapy for patients in whom first-line chemotherapy for metastatic disease has failed. Many newer chemotherapeutic agents have shown modest activity in urothelial carcinoma. Improved understanding of molecular biology and pathogenesis of urothelial carcinoma has opened avenues for the use of molecularly targeted therapies, several of which are being tested in clinical trials. Currently, several novel drugs seem particularly promising including inhibitors of the epidermal growth factor receptor pathway, such as cetuximab, and inhibitors of tumour angiogenesis, such as bevacizumab and sunitinib. Development of reliable molecular predictive markers is expected to improve treatment decisions, therapy development and outcomes in urothelial carcinoma. Funding of and participation in clinical trials are key to advancing the care of urothelial cancer patients. Current and emerging strategies in the medical management of urothelial carcinoma are reviewed.
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ABSTRACT: Monotherapy with intravenous vinflunine is indicated for the treatment of adults with advanced or metastatic transitional cell carcinoma of the urothelium after failure of a prior platinum-containing regimen. In this patient population, vinflunine added to best supportive care provided a survival advantage over the use of best supportive care alone and, given the nature of the disease, had an acceptable tolerability profile.Drugs & Therapy Perspectives 01/2012; 28(2). DOI:10.2165/11208720-000000000-00000
Article: Vinflunine.[Show abstract] [Hide abstract]
ABSTRACT: Vinflunine is a novel bifluorinated vinca alkaloid that appears to differ from other class members in terms of its tubulin-binding properties and inhibitory effects on microtubule dynamics. Notably, it demonstrated superior in vivo antitumour activity to that of vinorelbine in a range of transplantable murine and human tumours. In a randomized, open-label, multicentre phase III trial in adult patients with advanced transitional cell carcinoma of the urothelium who experienced progression after first-line platinum-containing chemotherapy (n = 370), median overall survival (OS; primary endpoint) was 6.9 months for intravenous vinflunine plus best supportive care (BSC) recipients versus 4.6 months for BSC alone recipients in the intent to treat (ITT) population. The difference in OS between treatment groups was not significant in the ITT population; however, there was a significant improvement in OS for vinflunine plus BSC recipients in the ITT population after adjusting for prespecified prognostic factors, and in the analysis of the eligible population (ITT population excluding baseline protocol violations). In the latter, median OS was 6.9 months with vinflunine plus BSC versus 4.3 months with BSC alone after a median follow-up of approximately 1.8 years and again after a median follow-up of approximately 3.6 years. Progression-free survival, objective response rate and disease control rate were significantly improved with vinflunine plus BSC versus BSC alone. The most frequent treatment-related adverse events in vinflunine recipients included myelosuppression (e.g. neutropenia) and gastrointestinal symptoms (e.g. constipation). In general, adverse events with vinflunine were noncumulative and medically manageable.Drugs 07/2010; 70(10):1283-93. DOI:10.2165/11204970-000000000-00000 · 4.13 Impact Factor
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ABSTRACT: Bladder cancer survival is consistently lower in female and black patients than in male and white patients. We compared trends and differences according to clinical, demographic and facility characteristics by patient race and gender to identify the impact of these characteristics on survival. We identified bladder transitional cell carcinoma cases diagnosed in 1993 to 2007 from the National Cancer Data Base. Trends in grade and stage distribution between 1993 and 2007 were analyzed. Survival differences by race and gender were compared using 5-year relative survival and multivariate Cox regression. There were 310,257 white male, 102,345 white female, 13,313 black male and 7,439 black female patients. Black and female patients had a higher proportion of muscle invasive tumors than white and male patients, and black patients had a larger proportion of higher grade tumors. The incidence of stage 0a and of high grade tumors significantly increased with time. Multivariate analysis showed a significantly lower HR in white females than in white males (HR 0.9) but a significantly higher HR in black males and females (HR 1.2). The higher mortality risk in black males and females was primarily limited to late stage disease (HR 1.3). Survival differences by race and gender are partially explained by differences in tumor and demographic characteristics in black males and females, and fully explained by these characteristics in white females. Treatment delays and under treatment due to comorbid conditions, age and other factors may also contribute to these disparities.The Journal of urology 03/2011; 185(5):1631-6. DOI:10.1016/j.juro.2010.12.049 · 3.75 Impact Factor