US pivotal studies of irinotecan in colorectal carcinoma.

Phase I trials of irinotecan (CPT-11 [Camptosar]), conducted at Johns Hopkins and the University of Texas, San Antonio, demonstrated some activity in patients with refractory advanced cancer. Three pivotal phase II studies of irinotecan in advanced colorectal carcinoma were conducted at The University of Texas, San Antonio, Mayo/North Central Cancer Treatment Group (NCCTG), and the CPT-11 Study Group in a total of 304 patients. All patients had received prior fluorouracil (5-FU) chemotherapy, and over 90% had progressed while on treatment within the last 6 months. The initial starting dose of irinotecan ranged from 100 to 150 mg/m2. The overall response rate was 12.8% (95% confidence interval, 9.1% to 16.6%) with a 15% response rate at a recommended starting dose of 125 mg/m2. The response durations and overall median survivals were similar in the three studies. The principal toxicities included diarrhea, nausea, vomiting, and neutropenia. Severe diarrhea was limited by use of an intensive loperamide regimen and appropriate dose modification. The three pivotal studies of irinotecan in advanced colorectal carcinoma demonstrate consistent response rates and duration, with manageable toxicity. Future studies will focus on the use of irinotecan in chemotherapeutically naive colorectal carcinoma, the adjuvant treatment of colon carcinoma, combination chemotherapeutic regimens, and treatment of other malignant diseases.