© 2003 European Society for Medical Oncology Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma

carboplatin–paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. Patients and methods: Chemotherapy naïve patients with EOC were treated with doxorubicin (50 mg/m2 day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m2/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. Results: Twelve patients with advanced EOC received a median of six cycles (range 2–6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m2/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. Conclusions: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m2). Key words: carboplatin, doxorubicin, ovarian carcinoma, weekly paclitaxe