Abstract

Adding anthracyclin to conventional platinum-based chemotherapy of ovarian cancer has been found to improve survival. The aim of this study was to evaluate the effect on survival on adding epirubicin to the standard treatment with carboplatin and paclitaxel. Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal, or peritoneal cancer FIGO stage IIB–IV were enrolled. They were randomized to receive six to nine cycles of paclitaxel (175 mg/m², 3 h iv) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m² iv prior to paclitaxel) on a 3-weekly schedule. The primary end point was progression-free survival, and 542 progression events were required to detect a hazard ratio of 0.786 or less. Patient characteristics were similar across the treatment arms. Residual disease less than 1 cm at surgery with no measurable disease before chemotherapy was reported in 328 patients (37%), with 159 in the TEC arm and 169 in the TC arm. A total of 63 patients had to be withdrawn from the study: 20 due to ineligibility, 32 due to hypersensitivity reaction to paclitaxel during the first or second course, and 11 due to withdrawal of informed consent, leaving 824 patients for the survival analysis. The median follow-up is 30 months for patients still alive. Progressive disease has been reported for 573 patients, and 326 have died. In the total group of patients, the median time to progression was 17.2 months in the TEC arm and 16.3 in the TC arm (P = 0.99). In the group with residual tumor of 1 cm or less, the median time to progression was 24.7 months in the TEC arm and 24.4 months in the TC arm (P = 0.94). In patients with more than 1 cm of residual tumor, the median time to progression in the TEC arm was 14.6 months and 13.8 months in the TC arm (P = 0.75). The median overall survival has not yet been reached. The addition of epirubicin to the standard carboplatin and paclitaxel treatment did not improve progression-free survival. The evaluation of effect on long-term survival awaits further follow-up.