Cisplatin and escalating doses of paclitaxel and epirubicin in advanced ovarian cancer. A phase I study

Abstract.

Purpose: The combination of paclitaxel and cisplatin is considered the standard regimen for advanced ovarian cancer (AOC). A meta-analysis has shown that the incorporation of anthracyclines into first-line chemotherapy might improve long-term survival by 7–10%. We designed a phase I–II study in patients with AOC using a combination of a fixed dose of cisplatin with paclitaxel and epirubicin both given at escalating doses every 3 weeks. The objectives of this study were to determine both the maximum tolerated dose (MTD) and the antitumor activity of this combination. Methods: Six different dose levels were planned. The starting doses were cisplatin 75 mg/m², paclitaxel 140 mg/m², and epirubicin 50 mg/m². The doses of paclitaxel were escalated in 20-mg/m² increments, alternating with 20-mg/m² increments of epirubicin. Ten patients with AOC entered the phase I study. Three patients each were enrolled at level I and level II and four patients at level III, and at each level, 15 courses were administered. Patients received a median of five courses. Results: Nonhematological toxicity was generally mild, except for grade 3 mucositis in one course at levels II and III, and grade 3 vomiting in one course at levels I and III. Hematological toxicities were grade 3–4 neutropenia in 60%, 47% and 60% of courses at levels I, II and III, respectively, and grade 3 anemia in one course at level III. At level III two of four patients developed a dose-limiting toxicity which was grade 4 neutropenia lasting more than 1 week. Conclusions: The MTD was reached at level II with cisplatin 75 mg/m², paclitaxel 160 mg/m², and epirubicin 50 mg/m². The phase II part of the study is currently ongoing.