EFFICACY AND SAFETY OF THE PACLITAXEL AND CARBOPLATIN COMBINATION IN PATIENTS WITH PREVIOUSLY TREATED ADVANCED OVARIAN-CARCINOMA - A MULTICENTER GINECO ATEURS-NATIONAUX-POUR-LETUDE-DES-CANCERS-OVARIENS) PHASE-II STUDY

Background. Platinum compounds are the most active drugs in ovarian ca ncer treatment; cisplatin and carboplatin demonstrated similar efficac ies but different toxicity profiles. Paclitaxel combined with cisplati n as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-ca rboplatin combination may be better tolerated than cisplatin-paclitaxe l. Design. The objective of the present study was to assess the effica cy and safety of the combination of paclitaxel and carboplatin in prev iously treated advanced ovarian cancer patients. Patients and methods. During or after platinum-based chemotherapy, 73 patients with progres sive advanced epithelial ovarian carcinoma were enrolled to receive ev ery four weeks a three-hour infusion of paclitaxel 175 mg/m(2) followe d by a 30-minute carboplatin infusion. The carboplatin dose was calcul ated to obtain the recommended area concentration-versus-time under th e curve of 5 mg.ml(-1).min. Results: Toxicity and response could be ev aluated for 72 and 62 patients, respectively. Eleven complete and 15 p artial responses gave an overall response rate of 42% (95% CI: 30%-54% ). Response rates for platinum-refractory patients and those with earl y (greater than or equal to 3 and <12 months) and late (>12 months) I: elapses were 25%, 33% and 70%, respectively. The respective median res ponse duration, the median progression-free survival and median overal l survival were 8, 6 and 14 months. Myelosuppression was the most freq uent and severe toxicity. Grade 3 and 4 neutropenia occurred, respecti vely in 30% and 23% of the cycles; 6% of the cycles benefited from med ullary growth factors. Only one episode of febrile neutropenia was obs erved. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neu ropathy developed in 47% of patients but was severe in only one patien t. One early death was attributed to progressive disease and possibly to therapy. Conclusion: This combined paclitaxel-carboplatin therapy i s effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.