A carboplatin-based regimen for the treatment of patients with advanced transitional cell carcinoma of the urothelium.

Abstract

Many patients with advanced transitional cell carcinoma are unable to receive cisplatin-based therapy. The efficacy and toxicity of a carboplatin-based regimen in the treatment of patients with advanced transitional cell carcinoma was therefore evaluated. Twenty-three patients with advanced transitional cell carcinoma were treated. Metastatic disease was present in 19 of 23 patients (83%) whereas 4 patients with T4, and/or N1, disease were treated. Patients were treated every 28 days with methotrexate, 30 mg/m2 intravenously (i.v.) on Days 1 and 15, along with leucovorin, 15 mg/m2 orally every 6 hours, 3 times daily beginning 24 hours after each methotrexate dose; vinblastine, 3 mg/m2 i.v. on Days 1 and 15; mitoxantrone, 15 mg/m2 i.v. on Day 1; and carboplatin, 300 mg/m2 i.v. on Day 1, adjusted for creatinine clearance (MVNCa). Dosage in subsequent cycles was adjusted according to hematologic toxicity. Median age was 70 years (range, 52-83 years) and median pretreatment creatinine clearance was 50 mL/min (range, 30-106 mL/min). Of 23 patients, 8 (34.8%) obtained a complete response, and 5 (21.7%) obtained a partial response. The overall response proportion was 56.5% (95% confidence interval, 34.5-76.8%). Median survival was 10 months (range, 1-44+ months). Toxicity was moderate. Grade 4 neutropenia occurred in 10 of 107 (9.3%) administered treatment cycles; Grade 4 thrombocytopenia occurred in 11 of 107, (10.3%). There were 4 episodes of febrile neutropenia (3.7% of cycles). Renal, neurologic, or otic toxicity were not observed. Age older than 70 did not appear to impact on response proportion, survival, and toxicity. The carboplatin-based MVNCa regimen is active in the treatment of patients with advanced transitional cell carcinoma and is well tolerated. Therapy with this regimen may be a less toxic alternative for patients for whom treatment with cisplatin is not an option.