title: [Early adjuvant intraportal chemotherapy with 5-fluorouracil after hepatic resection of colorectal metastasis: a preliminary clinical and pharmacokinetic study].
abstract: Intraportal continuous infusion of 5-FU (600 mg/m2/24 h during 7 days) was administered in the immediate postoperative course of 6 consecutive patients with colorectal metastases resected for cure (one segmentectomy and 5 nonanatomical local resections). One month later, a systemic continuous infusion of 5-FU was delivered at the same dose. The tolerance of intraportal chemotherapy was good despite 2 patients with mild digestive toxicity. The plasma concentrations of both unchanged 5-FU and 5,6-dihydro-5-FU (the primary metabolite of 5-FU), were determined in 2 patients using Gas Chromatography--Mass Spectrometry. The 5-FU clearance was higher after intraportal infusion than after systemic infusion (x 1.5 to 3). Hepatic extraction was variable (0.32-0.70) and lower than in reported experimental data on dogs (0.90-0.99). 5,6-dihydro-5-FU concentrations were constantly higher than 5-FU concentrations in plasma. The patient with lower hepatic extraction had the higher 5,6-dihydro-5-FU plasma concentrations. These findings suggest a predominant extrahepatic formation of plasmatic 5,6-dihydro-5-FU.
authors.affiliation: Service de gastro-entérologie, Institut J.-Paoli-I.-Calmettes, Marseille, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Seitz
authors.forename: C
authors.initials: C
authors.lastname: Aubert
authors.forename: M
authors.initials: M
authors.lastname: Giovannini
authors.forename: J R
authors.initials: JR
authors.lastname: Delpero
authors.forename: G
authors.initials: G
authors.lastname: Houvenaeghel
authors.forename: G
authors.initials: G
authors.lastname: Guerinel
authors.forename: Y
authors.initials: Y
authors.lastname: Carcassonne
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006498:Hepatectomy; D006801:Humans; D007263:Infusions, Parenteral; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011168:Portal System; D011184:Postoperative Period
chemical_list: D005472:Fluorouracil
vernacular_title: Chimiothérapie intraportale adjuvante précoce par le 5-fluoro-uracile après resection hépatique pour métastases d'origine colorectale: étude préliminaire clinique et pharmacocinétique.