M-VEC (methotrexate, vinblastine, epidoxorubicin and cisplatin), a new combined drug regimen in which epidoxorubicin has been substituted to adriamycin to reduce the toxicity of the original M-VAC chemotherapy, has been tested in 23 patients with locally advanced transitional cell bladder cancer (TCBC) (stage T2-T4 No Mo). After two to four courses, an objective response was observed in 19 patients, with 13 clinical complete responses. Seven patients underwent cystectomy after chemotherapy: one patient had no residual tumor on bladder specimens, five patients had a surgical eradication of the disease, while one patient had only a partial resection. Eight relapses of bladder carcinoma were observed, three among the surgically treated patients and five among patients who did not undergo cystectomy, with a median time-to-relapse of 9.7 months. Progression-free survival at 24 months was 52.3%. M-VEC regimen appears to be effective in locally advanced TCBC, with acceptable toxicity.