title: Role of leucovorin dosing and administration schedule.
abstract: Leucovorin (LV) is commonly administered in association with 5-fluorouracil (5-FU) to enhance its cytotoxic effects. In this paper, the cellular and clinical pharmacology of 5-FU potentiation by LV are reviewed, and the dosing and administration schedules are discussed in relation to reported clinical trials. In vitro experimental data suggest that prolonged cellular exposures to relatively low LV concentrations simultaneously with prolonged 5-FU administration are the optimal conditions to enhance 5-FU efficacy. Clinical studies of 5-FU/LV in metastatic colorectal carcinoma have established that 5-day bolus 5-FU with low-dose bolus LV injections yield therapeutic benefits equivalent to those obtained with intravenous bolus schedules using higher doses of LV. It remains to be determined, however, if bolus administration schedules are the optimal clinical treatment regimens. Infusional 5-FU/LV regimens appear to be a strategy worthy of further clinical investigation.
authors.affiliation: Centre de Recherche, Hôtel-Dieu de Montréal, Québec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Jolivet
mesh_terms: D000931:Antidotes / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil