Objectives: Carboplatin and paclitaxel can be applied safely and effectively as single agents for the treatment of ovarian cancer on a weekly basis. A multicenter, phase-I study was conducted to investigate the maximum tolerated dose of a weekly combination regimen.
Methods: We enrolled 21 patients with primary, surgically resected, advanced ovarian cancer (FIGO III/ IV) and a median age of 59 (range, 35 to 79) years. For a fixed dose of paclitaxel at 100 mg/m(2), carboplatin was administered at levels equating an area under the curve of 2.0 (6 patients), 2.5 (7 patients), and 3.0 (8 patients), respectively. Treatment schedule consisted of six cycles with drug delivery once a week, followed by a 2-week break, and another six cycles. After a treatment-free interval of 28 days, three more cycles were administered.
Results: No dose-limiting toxicity was observed at the first level. Three patients developed dose-limiting toxicity (thrombocytopenia, neutropenic fever, and grade 3 neuropathy) receiving carboplatin at area under the curve 2.5. Another three patients developed dose-limiting toxicity at the highest carboplatin dose, of whom two encountered refractory thrombocytopenia, whereas another experienced neutropenic fever despite prophylactic granulocyte-colony-stimulating factor use. Alopecia was documented in 17 patients. Neurotoxicity was usually mild to moderate. CA-125 concentrations normalized (<35 U/ml) in 13 of 19 patients (68%) by the end of therapy. A 50% response was observed in 16 of 19 subjects.
Conclusions: Weekly carboplatin and paclitaxel is a well-tolerated combination regimen in patients with primary, advanced ovarian cancer. The recommended dose for a phase II study is carboplatin at 100 mg/m(2) and carboplatin at area under the curve 2.0.
(c) 2002 Elsevier Science (USA).