Phase II trial of dose‐dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function
Open Access
Abstract
BACKGROUND. Cisplatin-based therapy is standard in patients with advanced urothelial carcinoma but a large proportion are ineligible due to renal impairment. The safety and activity of a dose-dense carboplatin-based regimen in this patient population were explored. METHODS. Patients with advanced urothelial carcinoma who were ineligible for cisplatin were eligible based on at least 1 of the following: 1) serum creatinine >1.5 mg/dL; 2) creatinine clearance of >30 mL/min/1.73 m2 and 2; and/or 3) prior nephrectomy. Patients received treatment with doxorubicin plus gemcitabine every other week × 5 cycles followed by paclitaxel plus carboplatin weekly × 12 cycles. RESULTS. Twenty-five patients were treated. Myelosuppression was the major toxicity, with 28% of patients experiencing grade 3–4 neutropenia; there were only 2 (8%) episodes of febrile neutropenia. Grade ≥3 nonhematologic toxicities were infrequent with the exception of grade ≥3 thrombotic episodes in 4 (16%) patients. There were 5 complete responses and 9 partial responses for an overall response rate of 56% (95% confidence interval [CI]: 35%–76%). The median survival was 15 months (95% CI: 11–30). At a median follow-up for survivors of 45 months, 7 (28%) patients are disease-free. CONCLUSIONS. Dose-dense sequential chemotherapy is tolerable and active in patients with urothelial carcinoma and renal impairment. Prolonged disease-free survival is achievable in a subset of patients with primary unresectable disease or lymph-node only metastases treated with carboplatin-based therapy ± surgical consolidation. Randomized trials are needed to define the optimal regimen in patients with advanced urothelial carcinoma and renal impairment. Cancer 2007 © 2007 American Cancer Society.Keywords
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