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


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 (<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.


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.
Vermorken
J B
JB
University Hospital 'Vrije Universiteit', Amsterdam, The Netherlands.
ten Bokkel Huinink
W W
WW
Kobierska
A
A
van der Burg
M E
ME
Forni
M
M
Piccart
M J
MJ
van der Putten
E
E
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D015251:Epirubicin; D002945:Cisplatin