[CPT-11 (irinotecan)--evidence from molecular and pharmacological studies and clinical applications]

Irinotecan (CPT-11) is a derivative of the chemotherapeutic agent Camptothecin. CPT-11 inhibits the nuclear enzyme topoisomerase I. It has demonstrated a broad spectrum of antitumor activity in preclinical tumor model systems. Significant advances have been made toward the understanding of the pharmacokinetics and schedule dependency of this agent. The principal dose limiting toxicities are diarrhea and leukopenia. CPT-11 has been evaluated using a variety of dosing schedules. Two main schedules have been studied and produce similar activity and side-effects: the "Japanese-North American" one where CPT-11 is given at a weekly dose of 100-150 mg/m2 for 4 consecutive weeks followed by a 2 week rest period, and the "European" one-350 mg/m2 every 21 days. CPT-11 has demonstrated significant clinical activity in the treatment of patients with gastrointestinal, pulmonary, gynecologic, and lymphoid malignancies. A recent randomized trial demonstrated a survival advantage in metastatic non-small cell lung cancer and previously untreated metastatic colorectal cancer. Further study of this agent to determine its role in combination chemotherapeutic regimens is currently underway.