Phase I/II study of the combination of carboplatin and paclitaxel as first-line chemotherapy in patients with advanced epithelial ovarian cancer

Purpose: We performed a phase I/II study evaluating the combination ofpaclitaxel and carboplatin as first-line chemotherapy in patients withadvanced ovarian cancer. The aim of this study was to define a feasible andsafe combination regimen that could be recommended for future phase IIIstudies.Design: This study was a parallel two-arm, non-randomized, open trial. Ina first step, carboplatin was administered at a fixed dose of AUC 5 andpaclitaxel was escalated in 25 mg/m² steps starting at 135mg/m². Paclitaxel was given as a three-hour infusion.Carboplatin was administered on day 1 following paclitaxel in one study armand 24 hours after paclitaxel infusion on day 2 in the other study arm.Carboplatin was escalated to AUC 6 and AUC 7.5 after the MTD for paclitaxelhad been defined. Treatment was repeated every three weeks.Patients: Sixty-one patients with untreated histologically confirmedepithelial ovarian cancer were recruited of whom 59 were found eligible andevaluable for toxicity. Thirty-three patients with bidimensionally measurabledisease were evaluable for tumor response.Results: We could not detect any advantage of the two-day schedule comparedwith the more convenient one-day schedule. Dose limiting toxicities wereneutropenia, thrombocytopenia, and neurotoxicity. Except for two patients,toxicity was acceptable and clinically managable. One patient died ofneutropenic sepsis and one further patient developed grade III peripheralneurotoxicity that did not resolve within two months after chemotherapy hadbeen terminated. Overall objective response rate was 70%. The MTD forpaclitaxel was 185 mg/m² and AUC 6 for carboplatin,respectively. Secondary prophylaxis with G-CSF did not allow further doseescalation and therefore is not generally recommended.Conclusions: Paclitaxel 185 mg/m² given as three-hourinfusion followed by carboplatin AUC 6 is a feasible and safe regimen and canbe recommended for phase III trials. Observed response rates justify furtherevaluation of this combination. A randomized phase III trial comparing athree-hour infusion of paclitaxel 185 mg/m² combined witheither carboplatin AUC 6 or cisplatin 75 mg/m² as first-linechemotherapy of advanced ovarian cancer has recently been initiated by ourgroup.