Phase II trial of dose‐dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function

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 <60 mL/min/1.73 m2; 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.

Bladder cancer

“…Objective response rates of 38-46% were achieved, with a tolerable toxicity profile. In another phase II trial for patients with advanced urothelial carcinoma and renal insufficiency, 25 patients were treated sequentially with dose-dense doxorubicin and gemcitabine, followed by paclitaxel and carboplatin [118 ]. Overall response rate was 56%, with a 15-month median survival.…”

Systemic therapy for bladder cancer – a medical oncologist’s perspective

“…To improve tolerability, further investigations have examined sequential treatment with carboplatin-gemcitabine then paclitaxel [50] . A sequential approach was similarly studied with dose-dense doxorubicin-gemcitabine followed by carboplatin-paclitaxel [51] . A four drug regimen of MTEC (methotrexate, paclitaxel, epirubicin, carboplatin) has been tested with a response rate of 60% (included CR rate of 30%) as first-line therapy [52] .…”

Chemotherapy in advanced bladder cancer: current status and future

“…In another trial, 25 patients with advanced urothelial carcinoma who were ineligible for cisplatin, received doses-dense sequential treatment with doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin. ORR was 56% and the treatment was well tolerated [57]. …”