Phase II trial of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma

BACKGROUND. This study was undertaken to determine whether the use of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin as first-line therapy increases the proportion of major responders and overall survival in patients with unresectable or metastatic transitional cell carcinoma (TCC) of the urothelial tract. METHODS, Twenty-nine patients with histologically confirmed TCC received methotrexate at a dose of 1000 mg/m(2) on Day 1 followed by leucovorin calcium rescue on Day 2 and vinblastine (3 mg/m(2)), doxorubicin (30 mg/m(2)), and cisplatin (70 mg/m(2)) (VAC) an Day 2. Therapy was recycled at 28-day intervals. RESULTS. Fourteen of 28 patients (50%; 95% confidence interval [CI], 31-69%) achieved a major response, including 6 pathologic or clinical complete responses (CR) and 8 partial responses (PR). Nine patients were rendered disease free after postchemotherapy surgical resection of residual disease (surgical CR), including five patients who had PR and four nonresponders to chemotherapy alone. Five of 18 patients with disease limited to lymph nodes attained CR, in contrast to only 1 of 10 patients with visceral metastatic disease. The median survival for the entire population was 13.6 months. CONCLUSIONS. The escalation of methotrexate to 1000 mg/m(2) in combination with vinblastine, doxorubicin, and cisplatin did not result in a response proportion or median survival superior to that observed with standard dose M-VAC. As previously observed in a Phase II trial of M-VAC, only the attainment of CR was associated with prolongation of survival. Cancer 1999:85:1145-50. (C) 1999 American Cancer Society.