Chemotherapy with methotrexate, carboplatin, mitoxantrone (Novantrone) and vincristine (Oncovin) in transitional-cell urothelial cancer.

Forty-four patients with either metastatic or locally advanced transitional cell carcinoma of the bladder were treated with the MCNO regimen (methotrexate 300 mg/m2 in 1,000 ml normal saline as a 4-hour infusion on days 1 and 14 with leucovorin rescue 15 mg 6-hourly for 6 doses; carboplatin 300 mg/m2 in 250 ml 5% distilled water as a 1-hour infusion on day 1; mitoxantrone (Novantrone) 10 mg/m2 in 100 ml 5% distilled water as a 30-min infusion on day 1, and vincristine (Oncovin) 1 mg/m2 as an intravenous bolus on days 1 and 14. Patients with metastatic disease were treated with 6 cycles, while patients with locally advanced disease were treated with 4 cycles of induction chemotherapy followed by cystectomy or radiotherapy. The overall response rate was 40%, with 15% complete response (CR). The responses were better for patients with locally advanced disease (CR 25%, partial response, PR, 31.25%, response rate, RR, 56.25%) than for those with metastatic disease (CR 8.3%, PR 20.83%, RR 29.1 %). The differences in these results were probably due to the bad performance status and the presence of visceral metastases in patients with generalized disease. The overall median survival was 14 months, with responders living longer (median survival 28.8 months in patients with locally advanced disease and 22.9 months in patients with metastatic disease) than non-responders (median survival 16 months in patients with locally advanced disease and 8.9 months in patients with metastatic disease). The difference in survival between responders and non-responders was statistically significant in both groups of patients. Toxicity was moderate, but manageable. The MCNO regimen appears to have a lower efficacy than that obtained with cisplatin-based regimens for the treatment of metastatic disease and rather similar efficacy for the treatment of locally advanced urothelial-cell cancer. Therapy with this regimen, though less toxic, may not be a reliable alternative in elderly patients with visceral metastases and a performance status of > or = 2.