Relationship between 5-fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU.

Abstract:

BACKGROUND:A phase II prospective trial was carried out to study the concept of 5-fluorouracil (5-FU) dose-intensity in patients with advanced colorectal cancer. Forty patients were treated with 5-FU plus leucovorin (LV), with individually increasing doses of 5-FU. A 5-FU pharmacokinetic follow up was performed and a relationship was sought between its metabolism and its response to treatment, and between 5-FU's toxicity and patient survival. METHODS:5-FU was administered weekly by 8 hour continuous infusion. The initial dose of 1000 mg/m2 was individually increased every 3 weeks by 250 mg/m2 steps, potentiated by 400 mg/m2 LV. 5-FU plasma concentrations were determined weekly by liquid chromatography. RESULTS:Eighteen overall objective responses and 22 minor responses, stabilizations, or progressions (NR) were observed. 5-FU plasma levels were significantly higher in cases of complete or partial response, whatever the dose. They reached about 2000 micrograms/l as early as the second dose level (1250 mg/m2). Only seven patients who experienced NR reached equivalent levels after the fourth step (1750 mg/m2). High 5-FU plasma levels were predictive of an objective response and better survival (difference not significant). The acute toxicity, whatever the type, was correlated with 5-FU levels > 3000 micrograms/l and not with the dose. CONCLUSIONS:This study shows the wide variability of 5-FU metabolism, whatever the dose, the clear relationship between 5-FU plasma levels, toxicity, and efficacy. This relationship points out the problem of the polymorphism of 5-FU metabolism, the usefulness of the therapeutic range determination and the usefulness of the individual 5-FU dose adaptation.

journal_name

Cancer

journal_title

Cancer

authors

Gamelin EC,Danquechin-Dorval EM,Dumesnil YF,Maillart PJ,Goudier MJ,Burtin PC,Delva RG,Lortholary AH,Gesta PH,Larra FG

doi

10.1002/(SICI)1097-0142(19960201)77:3<441::AID-CNC

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

441-51

issue

3

eissn

0008-543X

issn

1097-0142

pii

10.1002/(SICI)1097-0142(19960201)77:3<441::AID-CNC

journal_volume

77

pub_type

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