A phase I study of irinotecan in combination with amrubicin for advanced lung cancer patients.

Background: A combination phase I study was conducted in a cohort of lung cancer patients to determine the maximum tolerated dose (MTD) and toxicities of irinotecan (CPT-11), a topoisomerase I inhibitor, in combination with amrubicin (AMR), a topoisomerase II inhibitor, and to observe their antitumor activities.

Patients And Methods: Patients with lung cancer received AMR (35 - 40 mg/m2 given intravenously over 5 min) for 3 consecutive days, and CPT-11 (50 - 60 mg/m2 given intravenously over 90 min) after the completion of AMR infusion on days 1 and 8, every 3 weeks.

Results: In total, eleven patients were enrolled in this study. The most frequent toxicities were bone marrow suppression, particularly leucopenia and neutropenia, followed by infection, diarrhea and pneumonitis. As a consequence of these toxicities, the MTD and the recommended dose could not be determined. There were two partial responses, which included one patient with small cell lung cancer (SCLC) who had previously received chemotherapy and the other with previously untreated non-small cell lung cancer (NSCLC).

Conclusion: These data suggest that the combination of CPT-11 and AMR is not tolerated, as it mediates an unexpectedly strong myelosuppressive effect, and is inactive against both NSCLC and SCLC.