Irinotecan: a new treatment in metastatic colorectal cancer

Abstract

Objective. Historically, outcomes of metastatic colorectal cancer therapy have been disappointing, with fluorouracil (5-FU) producing response rates of no more than 15%. The addition of leucovorin increases response rates; however, survival rates are largely unaffected. Recently, the topoisomerase I inhibitor, irinotecan, has proved active in metastatic colorectal cancer and is indicated as second-line therapy following disease recurrence or progression after 5-FU-based therapy. More recently, irinotecan plus 5-FU-LV was compared with 5-FU-LV as first line treatment of colorectal cancer, showing impressive results. This article discusses the role of irinotecan, as a single agent and in combination with 5-FU-LV, in the treatment of advanced colorectal cancer. Data sources. A MEDLINE search was conducted using 5-fluorouracil, irinotecan, leucovorin, and metastatic colorectal cancer as primary search terms. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the European Society for Medical Oncology annual meetings were also identified and reviewed. Clinical literature was reviewed and analyzed. Data synthesis. Results of studies comparing irinotecan with continuos infusion 5-FU or best supportive care suggest that irinotecan is superior to either treatment as second-line therapy of metastatic colorectal cancer. Based on these study results, along with irinotecan's lack of cross-resistance with other chemotherapy agents and mechanism of action that differs from 5-FU, phase III trials evaluating the use of irinotecan in combination with 5-FU-LV as first-line treatment for advanced colorectal cancer were conducted. The results of a pivotal trial evaluating irinotecan plus 5-FU-LV in this setting show superior response rates (RRs), time to tumor progression (TTP), and median survival times (MSTs) when compared with 5-FU-LV alone. This combination represents a major advance in the treatment of metastatic colorectal cancer and should be considered the first-line treatment standard.