Carboplatin, cisplatin and paclitaxel in the treatment of patients with epithelial ovarian cancer

Background: Prognosis of advanced ovarian cancer is unsatisfactory. Chemoth erapy can be intensified combining active drugs at their highest possible d oses Patients and Methods. In this phase I/II trial, 77 untreated patients received escalating doses of paclitaxel (135, 155, 175, 195 and 215 mg/m(2) , infused over 3 hours) with carboplatin (AUC 3.6) and cisplatin (60 mg/m(2 )). Nine, 16, 13, 8 and 3 patients were treated at the five levels, respect ively. A further 28 patients were treated at the maximum tolerable dose (MT D). Results: Dose-limiting toxicities tone WHO grade 3 constipation, one gr ade 2 prolonged peripheral neurotoxicity and one grade 3 cardiac toxicity) occurred at 215 mg/m(2) in 3 out of 3 patients. MTD was reached at level 4 paclitaxel dose (195 mg/m(2)). Response was evaluated in 62 patients. A com plete response was achieved in 23 patients (37.1% - 95% CI 25.2-50.3), incl uding 16 (25.8%) pathological and partial response in 28 (45.2%), for an ov erall response rate of 82.3% (95% exact CL: 70.5%-90.8%). The probability o f response was affected by the degree of initial debulking (p = 0.002) and not by the paclitaxel dose. In patients with stage III-IV disease, median p rogression-free survival was 17 months (95% CI 14-25). After a median follo w-up of 28 months, median survival had not been reached; 2-year estimated s urvival was 67%. Conclusion: Paclitaxel can be safely given at the dose of 195 mg/m(2) in combination with carboplatin (AUC 3.6) and cisplatin (60 mg/ m(2)). This combination is active and safe and could be considered in clini cal settings requiring intensive short treatment.