科研之友
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摘要
OBJECTIVES To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with alpha = 0.12 and beta = 0.19. RESULTS A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy. UROLOGY 76: 923-926, 2010.
- 出版日期2010-10
