Chemotherapy of advanced ovarian cancer

Majority of ovarian cancer patients have advanced disease (stage III or IV) at diagnosis and the prognosis of these patients is poor in spite of aggressive surgery. Therefore chemotherapy has gained a fundamental role in the therapeutic approach of ovarian cancer. Platinum compounds in combination with alkylating agents and taxoids have the higher antitumor activity in ovarian cancer, while the role of anthracyclines remains controversial. Our 10-year experience with cisplatinum-based polychemotherapy in 196 advanced ovarian cancer patients previously untreated with chemotherapy is reported. 74 patients were treated with the combination cis-platinum and anthracyclines; 53 patients received the combination cis-platinum plus epirubicin alternated to cyclophosphamide plus 5-fluorouracil; 48 patients were treated with cis-platinum plus cyclophosphamide plus epirubicin and 21 patients were treated with the same combination with intraperitoneal administration of cisplatin. Our data confirm literature results of 55% remission rate, with 29% showing complete remissions. The median survival was 79 weeks and the overall 10-year survival was 13%. Complete responders had a median survival of 263 weeks and a 30% survival at 10 years. The main prognostic factors in our retrospective analysis were the objective remission, the size of residual tumor, the performance status and the stage. With the combination carboplatin (300-400 mg/sm) and cyclophosphamide (600 mg/sm) we observed 80% objective responses (23% complete responses) in 53 advanced ovarian cancer patients. The median overall survival in this group was 140 weeks. We carried out a phase II, non-randomized study of taxol in 54 ovarian cancer patients pretreated with platinum-compounds. The overall tolerability was good and an objective remission was observed in 47% of cases (8% complete remissions). The median survival was 68 weeks. As a consequence of our previous experience, a phase I dose-finding study with the combination carboplatin and taxol was started in our Division in 1994. Up to now, 22 chemotherapy untreated patients entered the study and the 5th dose level (taxol 175 mg/sm and carboplatin 350 mg/sm) has been completed without reaching the maximum tolerated dose. Our preliminary data suggest that the combination taxol-carboplatin is very active as the first-line chemotherapy in advanced ovarian cancer (73% objective remissions in 15 evaluated patients).