Modified M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for advanced transitional cell carcinoma of the urothelium

In 1992-1997, 34 patients (pts) with histologically confirmed advanced transitional cell carcinoma (TCC) of urinary bladder received chemotherapy with modified M-VAC regimen. Median age was 66 years (range 46-77 years). There were 30 males and 4 females. Five patients had histological grade II disease and 29 patients had histological grade III disease. Four patients had stage II disease, 22 stage III, and 8 stage IV. In 12 patients modified M-VAC was given in adjuvant setting, 14 patients received neoadjuvant chemotherapy, and 8 patients were treated due to metastatic disease. The tumor was resected prior to therapy in 18 patients (5 radical cystectomy and 13 partial cystectomy). Eight patients underwent TUR-BT. Chemotherapy regimen consisted of methotrexate 30 mg/m², given intravenously (i.v.) on day 1 (d. 1), and vinblastine 3 mg/m², doxorubicin 30 mg/m² and cisplatin 75 mg/m², all administered i.v. on day 2 (d. 2). All patients received hydration followed by furosemid before cisplatin administration. Intravenous serotinin receptor antagonists were used for prevention of vomiting. Treatment was given every 21 days. The relative dose intensity (RDI) of methotrexate was 0.44, vinblastine 0.44, doxorubicin 1.33 and cisplatin 1.43, respectively and the average RDI of modified M-VAC as compared to standard M-VAC was 0.91. Blood count, serum creatinine and 24-h creatinine clearance were tested prior to therapy. Weekly blood counts were performed during therapy. Results: The average number of cycles was 3 (range 1-7, total - 113 cycles). Neutropenia was the most frequent severe toxicity (5.9% grade III and 17.6% grade IV). Other side effects were as follows: grade I mucositis in 5 patients, and grade I serum creatinine elevation in 6 patients. All toxicity events were well manageable without treatment related deaths. Twenty two patients were evaluable for response assessment. Complete response (CR) was observed in 11 patients (50%), partial response (PR) in 6 patients (27%) and stable disease (SD) in 2 patients (9%). After neoadjuvant chemotherapy 57% patients were amenable to bladder preserving surgery. Median survival was 26, 25 and 18 months in adjuvant, neoadjuvant and metastatic settings, respectively. To our experience, modified M-VAC is effective in advanced TCC of urothelium with acceptable toxicity.