Phase III comparison of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) vs. doxorubicin and cisplatin (AC) in women with advanced primary or recurrent metastatic carcinoma of the uterine endometrium

Objectives. The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced endometrial cancer. Methods. Twenty-eight patients were randomly assigned to treatment with doxorubicin 30 mg/m(2) + cisplatin 70 mg/m(2) IV q 4 weeks vs. methotrexate 30 mg/m(2) IV days 1, 15, and 22, vinblastine 3 mg/m(2) IV days 2, 15, and 22, doxorubicin 30 mg/m(2) IV day 2, and cisplatin 70 mg/m(2) day 2 of a 4-week cycle. The trial was terminated prematurely due to slow accrual. Results. Prior to early closure of the protocol, there were 15 patients entered on the AC regimen and 13 to the MVAC regimen. There were 3 PR (20%) for AC and 3 CR (23%) and 3 PR (23%) for MVAC. Median PFS was 4.0 months for AC and 6.9 months for MVAC. Median survival was 13.2 months for AC and 16.8 months for MVAC. Toxicity was substantial for MVAC vs. AC with severe leukopenia seen in 69% vs. 33% of patients and severe thrombocytopenia 23% vs. 0%. No treatment-related deaths were seen. Discussion. MVAC and AC are active regimens in the treatment of advanced/recurrent or metastatic endometrial cancer. The premature closure of the protocol resulted in small patient numbers that left the protocol underpowered to address the primary objective of demonstrating improved CR rate for MVAC over AC. MVAC has substantial toxicity compared to AC and is not substantially superior to AC. MVAC cannot be considered as a standard for treatment in this patient population. (C) 2005 Elsevier Inc. All rights reserved.