IRINOTECAN - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND CLINICAL EFFICACY IN THE MANAGEMENT OF ADVANCED COLORECTAL-CANCER

Irinotecan (CPT-11) is a semisynthetic derivative of camptothecin. It and other camptothecin analogues/derivatives appear to exert their ant itumour activity by binding to topoisomerase I. The active metabolite of irinotecan, 7-ethyl-10-hyroxycamptothecin (SN-38), has demonstrated potent growth inhibition of human colorectal cancer cells in vitro, w ith superior activity to fluorouracil. In phase II clinical studies in patients with advanced colorectal cancer, objective response rates af ter irinotecan therapy ranged between 20.5 and 32%. These studies used a range of irinotecan regimens including 350 mg/m(2) once every 3 wee ks (Europe), 125 to 150 mg/m(2) once a week for 4 weeks followed by a 2-week drug-free interval (US) and 100 mg/m(2)/week or 150 mg/m(2) eve ry 2 weeks (Japan). The median duration of response ranged between 5.6 and 10.6 months. Disease stabilisation occurred in 30 to 71.2% of pat ients. Objective response rates to irinotecan therapy in patients who had received no prior chemotherapy were similar to those in patients p retreated with fluorouracil. Importantly, irinotecan also induced resp onses in some patients with tumours refractory to fluorouracil. Severe (grade 3 or 4) neutropenia and diarrhoea, which occurred in up to 40% of patients receiving irinotecan therapy in phase II studies, require careful monitoring and appropriate management. Thus, irinotecan is a valuable agent for the second-line treatment of patients with advanced colorectal cancer who fail to respond to or relapse after fluorouraci l therapy.