A multicenter phase II study of cisplatin (C), gemcitabine (G), and bevacizumab (B) as first-line chemotherapy for metastatic urothelial carcinoma (UC): Hoosier Oncology Group GU-0475

Abstract

5018 Background: Despite CG therapy, most metastatic UC patients die from their disease. Novel approaches are needed. Combining anti-angiogenic therapy with chemotherapy has improved outcomes in other malignancies, offering hope for similar improvements in UC patients. Methods: Metastatic or unresectable chemonaive UC patients (pts) with an ECOG performance status of 0–1 received C 70 mg/m2 iv d1, G 1,000–1,250 mg/m2 iv d1, 8, and B 15 mg/kg iv d1 on a q21d cycle for up to 8 cycles. Gemcitabine was reduced to 1,000 mg/m2 iv d1, 8 for all subsequent pts after 7 thromboembolic events were noted in the first 17 pts. The primary endpoint was progression free survival (PFS). The trial was designed to detect a 33% improvement in PFS from 7.5 months with traditional CG therapy to 11.25 months with CGB. Results: By December 2008, 45 pts were enrolled, with 43 evaluable for toxicity, 36 for response. Demographics include: 33 (77%) male, 10 (23%) female; median age 66 (Range: 41 - 78); 26 (60%) and 17 (40%) ECOG 0/1; 19 (44%) and 24 (56%) lymph node only / visceral metastases. PFS will be evaluated in May 2009 when all pts will have more than 6 month follow-up data. 14 (33%) and 6 (14%) pts experienced grade 3 or 4 hematologic toxicity (4 pts - thrombocytopenia, 2 pts - neutropenic fever). Grade 3 or 4 nonhematologic toxicity was observed in 24 (56%) and 9 (21%) pts (DVT/PE - 9 pts, CNS hemorrhage/proteinuria/hypertension - 1 pt each) Best RECIST response was: complete response 6 pts (17%, 95% CI 6–33%), partial response 18 pts (50%, 95% CI 33–67%); with overall response rate of 67% (95% CI 51–82%). Stable disease lasting at least 12 weeks was observed in 10 pts (28%, 95% CI 14–45%) and progressive disease in 2 pts (5%, 95% CI 1–19%). Conclusions: CGB demonstrates significant clinical activity in the first-line treatment of metastatic UC patients at the expense of considerable toxicity. The durability of disease control will be determined by assessment of PFS. A phase III trial to further define the toxicity risk vs. clinical benefit of bevacizumab addition to platinum-based doublets is planned in this population. [Table: see text]