Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy amd recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European organization for research and treatment of cancerprotocol no. 30924

Purpose: This randomized trial evaluated antitumor activity of and survival associated with high-dose-intensity chemotherapy with methotrexate, vinbla stine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulatin g factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). Patients and Methods: A total of 263 patients with metastatic or advanced T CC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). Results: Using an intent-to-treat analysis, at a median follow-up of 38 mon ths, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confide nce interval [Cl], 54% to 70%), On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%), The P v alue for the difference in CR rate was .009; and for the overall response, it was .06. There was no statistically significant difference in survival ( P = .122) or time to progression (P = .114), Progression-free survival was significantly better with HD-MVAC (P = .037; hazard ratio .75; 95% Cl .58 t o .98). The median progression-free survival time was 9.1 months on the HD- MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free sur vival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% Cl, 5.9% to 17.4%). Conclusion: With HD-MVAC, it was possible to deliver twice the doses of cis platin and doxorubicin in half the time, with fewer dose delays and less to xicity. Although a 50% difference in median overall survival was not detect ed, a benefit was observed in progression-free survival, CR rates, and over all response rates with HD-MVAC.