Seminars in oncology
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Seminars in oncology · Dec 1999
ReviewTopoisomerase I inhibitors in the treatment of colorectal cancer.
Over the past 10 years, a number of topoisomerase I inhibitors have entered into clinical trials and several of these have been evaluated in phase II and III studies to determine their activity in patients with advanced colorectal cancer. The most extensively studied of these has been irinotecan (CPT-II). In phase II trials in patients with colorectal cancer that was recurrent or refractory to 5-Ruorouracil (5-FU)based front-line therapy, response rates of 14% to 22% and median survival times of 8 to 10 months have been consistently reported by groups from Japan, Europe, and the United States using avariety of drug administration schedules Two recently reported phase III trials comparing CPT-II against infusional 5-FU or best supportive care demonstrated that CPT-II confers a survival advantage over either of the two other approaches. ⋯ In summary, extensive evaluation of topoisomerase I inhibitors has identified a significant degree of variability in clinical activity in patients with advanced colorectal cancer. To date, only one topoisomerase I inhibitor, CPT-II, has demonstrated a level of activity sufficient for it to become an integral component of treatment for patients with 5-FU-refractory colorectal cancer. Current and future studies will focus on the development of front-line regimens combining CPT-II and 5-FU for treatment of patients with advanced-stage disease, moving topoisomerase I inhibitors into the adjuvant therapy setting, and developing combined modality regimens of surgery, radiation, and topoisomerase I inhibitors for patients with locally advanced colorectal cancer.