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

• Published in: Oncology Vol. 57; no. 1; p. 10
• Main Authors: Vermorken, J B, ten Bokkel Huinink, W W, Kobierska, A, van der Burg, M E, Forni, M, Piccart, M J, van der Putten, E
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-1999
• Subjects: Adult; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - therapeutic use; Antineoplastic Agents - therapeutic use; Cisplatin - therapeutic use; Drug Administration Schedule; Epirubicin - administration & dosage; Epirubicin - adverse effects; Epirubicin - therapeutic use; Female; Humans; Leukopenia - chemically induced; Middle Aged; Ovarian Neoplasms - drug therapy; Thrombocytopenia - chemically induced; Treatment Outcome
• ISSN: 0030-2414
• DOI: 10.1159/000011994

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.
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 (<5 min) once every 3 weeks and studied at the following dose levels: 120, 135, 150, 180 and 200 mg/m2 (at least 3 patients per dose level). None of the patients received hematopoietic growth factors. We defined the maximum tolerated dose (MTD) as the dose at which we observed WHO grade 4 hematologic toxicity in >/=50% and/or WHO grade 3 nonhematologic toxicity in >/=30% of the patients.
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.
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.