Efficacy and toxicity of irinotecan in patients with colorectal cancer.
In six published phase II trials, irinotecan (CPT-II; Camptosar; Pharmacia & Upjohn Co, Kalamazoo, MI) has demonstrated consistent activity with response rates of approximately 13% to 27% in patients with advanced colorectal cancer (CRC) refractory to 5-fluorouracil (5-FU) therapy. Similar response and median survival rates have been achieved using either the US regimen (once a week for 4 weeks followed by a 2-week rest) or the European regimen (once-every-3-week schedule). The optimal administration schedule for irinotecan is uncertain. Phase II evaluation of a biweekly administration schedule in a similar group of patients produced similar response rates. With all schedules tested, the most common toxicities remain delayed diarrhea, neutropenia, and nausea and vomiting. The most common toxicity, late diarrhea, can be ameliorated using high-dose loperamide. Irinotecan has been explored as a single agent in patients with newly diagnosed CRC and has generated response rates in the range of 19% to 32% and a median survival time of approximately 12 months, suggesting a level of antitumor activity similar to that observed with 5-FU and leucovorin. Two recently completed phase III studies in 5-FU-refractory patients have shown that treatment with irinotecan confers a survival advantage compared with treatment with infusional 5-FU or best supportive care. Current studies focus on the activity of irinotecan as part of combined chemotherapy in patients with newly diagnosed advanced-stage CRC, as part of combined-modality therapy with radiation therapy, and as adjuvant chemotherapy for patients with locally advanced CRC.
Rothenberg
M L
ML
University of Texas Health Science Center at San Antonio and The Cancer Therapy and Research Center, USA.
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis; D016879:Salvage Therapy; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin