5-Fluorouracil in colorectal cancer: rationale and clinical results of frequently used schedules

Anti-cancer Drugs
Y J KammC J Punt

Abstract

Colorectal cancer is one of the most frequent cancers in the western world. Approximately half of the patients will die of their disease because of metastases. The most active cytotoxic agent used to date is 5-fluorouracil (5-FU). However, clinical responses are achieved only in a minority of patients. Based on the current knowledge of the mechanism of action of 5-FU, many attempts have been made to improve the clinical results. These include the use of biochemical modulators and different methods of administration, and these are the subject of this review. Specifically, of five different modulators, i.e. leucovorin, methotrexate, interferon-alpha, N-(phosphonacetyl)-L-aspartate and trimetrexate glucuronate, the biochemical background and the clinical results obtained with these modulators are discussed. In order to get more insight, an overview of the 5-FU metabolism has been given. In addition, the different methods of systemic administration of 5-FU as well as possible mechanisms underlying 5-FU resistance are described.

Citations

Mar 4, 2000·Advanced Drug Delivery Reviews·W WolfV Waluch
Oct 17, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S Garattini, C La Vecchia
Sep 6, 2011·Bioorganic & Medicinal Chemistry Letters·Li-Hua HuangHong-Min Liu
Mar 10, 2020·PLoS Genetics·Ke WangStephan Schiffels

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