Experience with 5FU + L-Leucovorin
The mainstay of treatment for patients with metastatic colorectal cancer is chemotherapy with the combination of 5-Fluorouracil (5FU) and Leucovorin (LV) 1. This treatment has resulted in a response rate of 23% compared to 11% for 5FU in nine randomized trials of patients with previously untreated metastatic colorectal cancer 2. When compared to 5FU the odds ratio for response was 0.45 favouring 5FU + LV. The clinical modulation of 5FU antitumor effects supported the experimental studies in which the addition of LV in vitro led to increased cytotoxicity. This was related to stabilization of the thymidylate synthase (TS) folate and fluorodeoxyuridine monophosphate (FdUMP) complex and increased TS inhibition. Many questions of regarding the optimal dose of 5FU and LV and schedule of adminstration remain unresolved at present. The importance of the 1-LV in the antitumor effect of 5FU and the potential for interference of d-LV in the action of 1-LV must also be addressed.
KeywordsClin Oncol Metastatic Colorectal Cancer Folinic Acid Racemic Mixture Advanced Colorectal Cancer
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- 2.The advanced colorectal cancer meta-analysis project. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate. J Clin Oncol 1992; 10: 896–903.Google Scholar