A phase I trial of irinotecan alternating with epirubicin in patients with advanced malignancies.

OBJECTIVES: 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.