A phase i study of pegylated liposomal doxorubicin and irinotecan in patients with solid tumors

Background: Preclinical studies have shown synergism between topoisomerase I and II inhibitors. Methods: We conducted a phase I study evaluating the combination of pegylated liposomal doxorubicin and irinotecan in patients with previously treated solid tumors. Results: Twelve patients were enrolled. The median age was 62 years (range 19-72). The most common grade 3/4 toxicities were neutropenia (dose-limiting toxicity), diarrhea and nausea/vomiting. The maximal tolerated dose and recommended schedule were pegylated liposomal doxorubicin 20 mg/m² over 60 min on day 1, followed by irinotecan 100 mg/m ² over 90 min on days 1 and 8 of a 21-day cycle. There were no objective clinical responses, but 5 patients achieved stable disease lasting a median of 11 weeks duration (range 2-35). Conclusions: This regimen should be further studied in patients with tumors known to have a sensitivity to both topoisomerase I and II inhibitors such as ovarian and small cell carcinoma.