A phase II study of high-dose epirubicin in ovarian cancer patients previously treated with cisplatin

Background: In vitro data demonstrated a dose-response relationship for dox orubicin in ovarian cancer cell lines. However, this dose-response question for anthracyclines has never been adequately addressed in ovarian cancer p atients. A phase I study with epirubicin gave support to these in vitro fin dings and recommended a dose of 150 mg/m(2) for phase II testing. Patients and methods: The present report concerns the final analysis of an EORTC-Gynecological Cancer Cooperative Group (GCCG) phase II study of high- dose epirubicin (HDE) in cisplatin-pretreated patients with epithelial ovar ian cancer. A total of 100 eligible patients were included; 34 had progress ed during first-line therapy (group 1), 17 had persistent disease after fir st-line therapy (group 2) and 49 had relapsed following an initial response to first-line therapy (group 3). All patients had measurable or evaluable disease, were aged < 75 years, had a WHO performance status 0-2, had adequa te vital organ function and gave consent. Epirubicin was administered by ra pid i.v. infusion at a dose of 150 mg/m(2) and given at three-week interval s. Escalation to 180 mg/m(2) was to be carried out if white blood cell nadi r count was > 2.0 x 10(9)/l and platelet nadir count was > 75 x 10(9)/l. Results: A total of 361 HDE treatment cycles were administered, the median number per patient being 4. Of the 85 patients who received at least two cy cles of protocol treatment, 26 (31%) did not have any dose modification, 23 (26%) had dose reduction, while 36 (43%) had the dose increased to 180 mg/ m(2), at least for one cycle. The response rate in all eligible patients wa s 20% (95% confidence interval 13%-30%), 15% in group 1, 12% in group 2 and 27% in group 3. Patients with a cisplatin-free interval of > 12 months res ponded in 41%. The median duration of response was nine months (range 19 we eks to 3 years). Main toxicities were myelosuppression (leucopenia, neutrop enia), nausea, vomiting, alopecia and mucositis. There were three cases of excessive toxicity leading to early discontinuation of HDE treatment and in one patient this contributed to death. No serious cardiotoxicity was recor ded. Conclusions: It is concluded that HDE is active in platinum-pretreated pati ents with epithelial ovarian cancer and should be further studied in first- line in combination with paclitaxel and a platinum compound.