Phase II trial of methotrexate, vinblastine, doxorubicin, and cisplatin in advanced/recurrent carcinoma of the uterine cervix and vagina.

A phase II combination chemotherapy protocol combining methotrexate, vinblastine, doxorubicin, and cisplatin was designed to evaluate tumor response and survival in patients with advanced/recurrent cervix and vaginal cancer. Twenty-nine patients with advanced/recurrent cervix cancer and three patients with advanced vaginal cancer who had not previously received cytotoxic chemotherapy were assigned to chemotherapy treatment at 4-week intervals with methotrexate 30 mg/m2 i.v., Day 1, vinblastine 3 mg/m2 i.v., Days 2, 15, and 22, doxorubicin 30 mg/m2 i.v., Day 2, and cisplatin 70 mg/m2 i.v., Day 2. After a median of 4 cycles (maximum number 2 cycles beyond complete regression; 6 cycles with stable regression); we observed objective regressions in all 3 patients with vaginal cancer and 19 patients (66%, 95% CI = 46.82) with cervix cancer including complete regression in 6 patients (21%, 95% CI = 8.40) and partial regression in 13 patients (45%, 95% CI = 26.64). Median overall survival was 11.5 months (range 1.1-54+). Median survival of responders was 12.8 months (range 3.6-54+). Toxicity included neutropenia, alopecia, nausea, emesis, and stomatitis. Although grade 3 and 4 neutropenia was observed in over half of the patients, there were no treatment-related deaths. In conclusion, MVAC is a highly active outpatient chemotherapy regimen in patients with advanced/recurrent cervix cancer, achieving a high complete and partial response rate with moderate hematologic toxicity. These results need to be confirmed by phase III trial in advanced disease patients and MVAC may be a suitable regimen for investigation in neoadjuvant chemotherapy trials in poor prognosis, previously untreated patients.