title: Biochemical modulation of 5-FU in systemic treatment of advanced colorectal cancer.
abstract: Randomized studies have tested a variety of strategies to improve the activity of 5-fluorouracil (5-FU) in colorectal cancer patients. Results from 14 randomized trials comparing 5-FU administered via intravenous (i.v.) bolus either as a single agent or modulated by leucovorin indicate a significantly higher response rate with 5-FU/leucovorin (25% vs 13% of assessable patients). Sequential methotrexate followed by i.v. bolus 5-FU is associated with a higher response rate. Continuous infusion schedules also produce superior response rates compared to bolus 5-FU alone. Published meta-analyses indicate a small, but statistically significant, survival advantage for methotrexate/5-FU and infusional 5-FU, but not for leucovorin-modulated 5-FU. Although the incidence of hand-foot syndrome is higher with protracted infusional 5-FU, the incidence of other toxicities including myelosuppression, diarrhea, and mucositis is low. Oral administration of 5-FU may simulate infusional schedules while avoiding catheter-related complications.
authors.affiliation: Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland, USA. jgrem@helix.nih.gov
authors.forename: J L
authors.initials: JL
authors.lastname: Grem
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D015201:Meta-Analysis as Topic; D008727:Methotrexate / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic
chemical_list: D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate