Perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for poor risk transitional cell carcinoma of the bladder: an Eastern Cooperative Oncology Group pilot study. A total of 18 patients with locally advanced transitional cell carcinoma of the bladder underwent 2 preoperative cycles of chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin followed by radical cystectomy and 2 postoperative cycles of chemotherapy. Radical cystectomy was performed in 17 of 18 patients (94%) with a pathological partial response in 3 (17%) and a pathological complete response in 2 (11%), for an over-all response rate of 28% (95% confidence limits 10 to 53%). At 23-month median followup 9 patients (50%) remained without evidence of recurrent disease, while 9 (50%) died of metastatic bladder cancer. Average relative dose intensity of all therapy given was 78%. Hematological toxicity was moderate, with no septic deaths or bleeding complications. However, 4 thromboembolic events occurred. While downstaging of the primary bladder tumor can occur with this perioperative schedule our results were not as impressive as some previously reported findings. The incidence of thromboembolic events is worrisome. 