title: Gemcitabine increases systemic 5-fluorouracil exposure in advanced cancer patients.
abstract: A number of recent clinical trials testing the combination of 5-fluorouracil (5-FU) and gemcitabine in patients with advanced pancreatic adenocarcinoma have shown a significant clinical response rate, but also significant toxicity. As the two antimetabolites may interact at several biochemical levels along their pathways of activation, we investigated whether gemcitabine (GEM) affects 5-FU pharmacokinetics in cancer patients. Thus, we compared 5-FU pharmacokinetics in two groups of patients with various cancers who received the same schedule of 5-FU and folinic acid (FUFA), with or without GEM. There was a significant increase in systemic (5-FU) exposure and toxicity in the FUFA plus GEM group. Our finding may be useful in designing future studies of the combination in order to reduce the occurrence of side-effects and to maximise the antitumour activity.
authors.affiliation: Section of Oncology, Department of Human Pathology and Oncology, Siena University School of Medicine, Viale Bracci 11, 53100 Siena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Correale
authors.forename: D
authors.initials: D
authors.lastname: Cerretani
authors.forename: S
authors.initials: S
authors.lastname: Marsili
authors.forename: D
authors.initials: D
authors.lastname: Pozzessere
authors.forename: R
authors.initials: R
authors.lastname: Petrioli
authors.forename: S
authors.initials: S
authors.lastname: Messinese
authors.forename: M
authors.initials: M
authors.lastname: Sabatino
authors.forename: F
authors.initials: F
authors.lastname: Roviello
authors.forename: E
authors.initials: E
authors.lastname: Pinto
authors.forename: G
authors.initials: G
authors.lastname: Francini
authors.forename: G
authors.initials: G
authors.lastname: Giorgi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine