IRINOTECAN IS AN ACTIVE AGENT IN UNTREATED PATIENTS WITH METASTATIC COLORECTAL-CANCER

Purpose: To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metast atic colorectal cancer. Patients and Methods: Forty-one chemotherapy-n aive patients with measurable metastatic colorectal cancer were treate d with a 90-minute infusion of irinotecan 125 mg/m(2) administered wee kly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess t opoisomerase-I (Topo-I) activity were obtained from 11 patients. The p harmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients. Results: Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%), The medi an response duration was 8.1 months (range, 4.0 to 16.0) and the media n survival time wets 12.1 months (range, 2.1 to 21.7) for all 41 patie nts. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutr openia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rare of 56%; a significant reduction in the incidence of severe diarrhea t o 9% was noted with strict adherence to an antidiarrheal regimen of lo peramide and diphenhydramine. No correlations were seen between pharma cokinetics of irinotecan/SN-38 and the clinical parameters of response , survival, or incidence of diarrhea. Conclusions: Irinotecan has acti vity in the treatment of patients with metastatic colorectal cancer. S trict adherence to an antidiarrheal regimen of diphenhydramine/loperam ide significantly reduced the incidence of diarrhea; the agent was the reafter well tolerated in the majority of patients. (C) 1996 by Americ an Society of Clinical Oncology.