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

Purpose: The combination of paclitaxel and cisplatin is considered the stan dard regimen for advanced ovarian cancer (AOC). A meta-analysis has shown t hat the incorporation of anthracyclines into first-line chemotherapy might improve long-term survival by 7-10%. We designed a phase I-II study in pati ents with AOC using a combination of a fixed dose of cisplatin with paclita xel and epirubicin both given at escalating doses every 3 weeks. The object ives 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/m(2), paclita xel 140 mg/m(2), and epirubicin 50 mg/m(2). The doses of paclitaxel were es calated in 20-mg/m(2) increments, alternating with 20-mg/m(2) increments of epirubicin. Ten patients with AOC entered the phase I study. Three patient s 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 medi an 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 I II, respectively, and grade 3 anemia in one course at level III. At level I II two of four patients developed a dose-limiting toxicity which was grade 4 neutropenia lasting more than I week. Conclusions: The MTD was reached at level II with cisplatin 75 mg/m(2) paclitaxel 160 mg/m(2), and epirubicin 50 mg/m(2). The phase II part of the study is currently ongoing.