[Early adjuvant intraportal chemotherapy with 5-fluorouracil after hepatic resection of colorectal metastasis: a preliminary clinical and pharmacokinetic study].
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.
Seitz
J F
JF
Service de gastro-entérologie, Institut J.-Paoli-I.-Calmettes, Marseille, France.
Aubert
C
C
Giovannini
M
M
Delpero
J R
JR
Houvenaeghel
G
G
Guerinel
G
G
Carcassonne
Y
Y
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
D005472:Fluorouracil
Chimiothérapie intraportale adjuvante précoce par le 5-fluoro-uracile après resection hépatique pour métastases d'origine colorectale: étude préliminaire clinique et pharmacocinétique.