Possible survival benefit of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin combination therapy (HD-MVAC) over conventional MVAC in metastatic urothelial carcinoma patients.

Eight patients with metastatic urothelial carcinoma received high-dose (HD)-MVAC therapy, which consisted of methotrexate (30 mg/m2) on day 1, vinblastine (3 mg/m2) on day 2, doxorubicin (30 mg/m2) on day 2 and cisplatin (70 mg/m2) on day 2 (14-day cycle). Patients were treated with granulocyte colony-stimulating factor (G-CSF) (100 microg) subcutaneously from day 4 to 10. For comparison, 7 patients with metastatic urothelial carcinoma who received conventional (C)-MVAC (28-day cycle) were enrolled in this study. Overall survival in the HD-MVAC group was significantly better than that in the C-MVAC group (p = 0.012, log rank test). The overall response rate for measurable metastatic lesions was similar in both groups (HD-MVAC, 62.5% vs. C-MVAC, 57.1%, p =0.622). The patients in the HD-MVAC group were able to receive significantly more courses than the C-MVAC group (HD-MVAC, median 3 courses vs. C-MVAC, 2 courses, p=0.045, Student's t test). The frequency of grade 3/4 toxicities was not statistically different between the 2 groups. HD-MVAC therapy rather than C-MVAC therapy may be advocated as a first-line chemotherapy for metastatic patients, since HD-MVAC is associated with a shorter period required for each course, a lower frequency of dose reduction and a possible benefit in terms of overall survival.