Current Status of Colorectal Cancer: CPT-11 (Irinotecan), a Therapeutic Innovation

Abstract

Colorectal cancer affects around 5% of the population in Westernised countries and is associated with a high level of morbidity and mortality. Overall, around 50% of patients can expect to be fully cured by surgery, along with recent improvements in survival due to the use of adjuvant therapy. However, in patients who develop metastatic disease, the prognosis is poor, and the appropriateness of anticancer chemotherapy in such patients has been controversial. Nevertheless, there is increasing evidence that chemotherapy can extend life expectancy in colorectal cancer and that in metastatic disease patients achieve a significant benefit from early rather than late chemotherapy. For first-line treatment of metastatic colorectal cancer, the best available regimens have been those which include 5-fluorouracil (5-FU) and folinic acid; a meta-analysis of nine randomised clinical studies of such regimens produced a mean response rate of 23%. However, in those who fail or relapse, there has been no established second-line alternative. The development of CPT-11 (Campto, irinotecan), a specific inhibitor of topoisomerase I, represents a significant advance in the management of colorectal cancer. Following encouraging observations of sustained activity in colon cancer cell lines, including those having the MDR phenotype, clinical studies of CPT-11 monotherapy in both chemotherapy-naive and pretreated patients with advanced colorectal cancer demonstrated response rates at least equivalent to those achieved with first-line 5-FU/folinic acid combination therapy. This indicates that CPT-11 does not exhibit cross-resistance with 5-FU, making it the first effective second-line agent in this setting. Further studies are ongoing to define the optimum dosage schedule for CPT-11 and to assess the utility of CPT-11 as a single agent in second-line therapy, or combined with 5-FU and other anticancer agents as first-line therapy. In conclusion, CPT-11 offers a different cytotoxic approach that may complement the use of 5-FU/folinic acid in colorectal cancer in the future.