Purpose: We performed a phase I/II study evaluating the combination of paclitaxel and carboplatin as first-line chemotherapy in patients with advanced ovarian cancer. The aim of this study was to define a feasible and safe combination regimen that could be recommended for future phase III studies.
Design: This study was a parallel two-arm, non-randomized, open trial. In a first step, carboplatin was administered at a fixed dose of AUC 5 and paclitaxel was escalated in 25 mg/ m2 steps starting at 135 mg/m2. Paclitaxel was given as a three-hour infusion. Carboplatin was administered on day 1 following paclitaxel in one study arm and 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 paclitaxel had been defined. Treatment was repeated every three weeks.
Patients: Sixty-one patients with untreated histologically confirmed epithelial ovarian cancer were recruited of whom 59 were found eligible and evaluable for toxicity. Thirty-three patients with bidimensionally measurable disease were evaluable for tumor response.
Results: We could not detect any advantage of the two-day schedule compared with the more convenient one-day schedule. Dose limiting toxicities were neutropenia, thrombocytopenia, and neurotoxicity. Except for two patients, toxicity was acceptable and clinically managable. One patient died of neutropenic sepsis and one further patient developed grade III peripheral neurotoxicity that did not resolve within two months after chemotherapy had been terminated. Overall objective response rate was 70%. The MTD for paclitaxel was 185 mg/m2 and AUC 6 for carboplatin, respectively. Secondary prophylaxis with G-CSF did not allow further dose escalation and therefore is not generally recommended.
Conclusions: Paclitaxel 185 mg/m2 given as three-hour infusion followed by carboplatin AUC 6 is a feasible and safe regimen and can be recommended for phase III trials. Observed response rates justify further evaluation of this combination. A randomized phase III trial comparing a three-hour infusion of paclitaxel 185 mg/m2 combined with either carboplatin AUC 6 or cisplatin 75 mg/m2 as first-line chemotherapy of advanced ovarian cancer has recently been initiated by our group.