Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: A multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group

Abstract

Purpose: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. Patients and Methods: Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status ≤ 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m2 and cisplatin 75 mg/m 2 every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. Results: Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P = .017), median time to progression (TTP; 9.4 v6.1 months; P = .003) and median survival (14.2 v9.3 months; P = .026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P = .005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P = .089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P = .006), thrombocytopenia (5.7% v 0.9%; P = .046), and neutropenic sepsis (11.6% v 3.8%; P = .001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. Conclusion: MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma. © 2004 by American Society of Clinical Oncology.