A phase I trial of irinotecan alternating with epirubicin in patients with advanced malignancies.
OBJECTIVE
This phase I study was conducted to evaluate the combination of irinotecan, a topoisomerase I inhibitor, with epirubicin, a topoisomerase II inhibitor, when administered sequentially on a once-every-three week basis.


METHODS
Irinotecan was administered at doses ranging from 100 to 150 mg/m(2) intravenously over 90 minutes, 24 hours before epirubicin, in doses from 30 to 60 mg/m(2), every 3 weeks. Toxicity assessments were performed weekly. Tumor evaluation by radiographic and physical examination was performed after every 3 cycles using Response Evaluation Criteria in Solid Tumors.


RESULTS
Eighteen patients with metastatic solid tumors were enrolled in this study. The maximum tolerated dose and recommended phase II dose was irinotecan 150 mg/m(2) and epirubicin 30 mg/m(2). Dose-limiting toxicities were primarily neutropenia. Other toxicities at this dose level were mild. Three patients with colon cancer, 1 patient with renal cell cancer and 1 patient with adenosquamous cell carcinoma of the ethmoid sinus had stable disease. No objective responses were observed.


CONCLUSIONS
The maximum tolerated dose and recommended phase II dose for irinotecan and epirubicin administered 24 hours apart every 3 weeks was 150 mg/m(2) and 30 mg/m(2), respectively. Higher doses were limited by significant hematologic toxicity and fatigue.
Goff
Laura W
LW
Vanderbilt University, Nashville, TN 37232, USA. laura.williams.1@vanderbilt.edu
Rothenberg
Mace L
ML
Lockhart
A Craig
AC
Roth
Bruce J
BJ
VerMeulen
Wendy L
WL
Chan
Emily
E
Berlin
Jordan D
JD
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D015251:Epirubicin; D000077146:Irinotecan; D002166:Camptothecin