M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for poor prognosis patients with urothelial tumors and effect of dose intensity.

The effects of the M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen, which has been reported to improve the outcome of patients with urothelial cancers, were studied on 41 patients treated at our hospital. The patients were divided into adjuvant (24 patients), neoadjuvant (5 patients), and salvage (12 patients) groups. We investigated the dose intensity, the cause-specific survival, response rate and toxicities in the three groups. Although 36 patients received > or = 95% of the initial doses projected, the mean dose intensity (+/-standard deviation) in the adjuvant, neoadjuvant, and the salvage groups was 77 (+/-11), 73 (+/-4), and 74 (+/-12)%, respectively. The five-year cause-specific survival in the adjuvant group was 69% (95% confidence limit: 50-88%). Only 2 of the 5 patients (40%) in the neoadjuvant group survived 23 months after the initiation of the treatment, and all patients in the salvage group died of cancer or treatment-related toxicity within 33 months. The median survival was 38 months in the adjuvant group, 21 months in the neoadjuvant group, and 7 months in the salvage group. A dose intensity > or = 75% did not improve survival in any group. The overall response rate was 33% in 15 patients with evaluable lesions. A complete response was noted in 1 patient and a partial response was noted in 1 patients. Two patients died of treatment-related complications. Nausea and vomiting were observed in all patients. Leukopenia, thrombocytopenia and anemia > or = WHO grade 3 were observed in 25 (61%), 4 (10%), and 7 (17%) patients, respectively. Thrombocytopenia, anemia, and pyrexia > or = grade 3 were seen relatively more often in the patients receiving a dose intensity < 75%. Stomatitis > or = grade 3 appeared to be more frequent in the patients receiving a dose intensity > or = 75%. Adjuvant M-VAC might be beneficial, while its efficacy was limited in the neoadjuvant and salvage settings. Although dose intensity is considered to be important, it did not appear to be related to survival, the response rate, or the toxicity of M-VAC.