Phase I study of high-dose epirubicin in platinum-pretreated patients with ovarian carcinoma.

Abstract

BACKGROUND: In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines. However, this dose-response question for doxorubicin was never carefully addressed in OC patients. These data and the more favorable toxicity profile of the anthracycline analogue epirubicin prompted us to study high-dose epirubicin (HDE) in relapsed OC patients. PATIENTS AND METHODS: This phase I study included 19 OC patients with measurable or evaluable disease and no more than one prior (cisplatin-containing) chemotherapy regimen. Dose escalation was not allowed in individual patients. Epirubicin was administered by rapid intravenous infusion (/=50% and/or WHO grade 3 nonhematologic toxicity in >/=30% of the patients. RESULTS: The MTD was 200 mg/m2, with DLT being both hematologic (leukopenia and/or thrombocytopenia) and nonhematologic (mucositis). Objective responses were observed in 6 patients (response rate 32%), 3 of them occurring in 10 patients with primary platinum resistance. CONCLUSIONS: HDE is tolerable and has activity in second-line after cisplatin-based chemotherapy in OC patients. The recommended dose for phase II trials in such patients is 150 mg/m2, with escalation to 180 mg/m2 if toxicity permits.Clinical TrialClinical Trial, Phase IJournal Articleinfo:eu-repo/semantics/publishe