Relationship between 5-fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU
✍ Scribed by Erick C. Gamelin; Etienne M. Danquechin-Dorval; Yvan F. Dumesnil; Philippe J. Maillart; M. J. Goudier; Pascal C. Burtin; Remy G. Delva; Alain H. Lortholary; Paul H. Gesta; Francis G. Larra
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 977 KB
- Volume
- 77
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
BACKGROUND.
A phase I1 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/m' 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 significantlv higher in cases of complete or partial response, whatever the dose. They reached about 2000 gg/l as early as the second dose level (1250 mg/m'). Only seven patients who experienced NR reached equivalent levels after the fourth step (1750 mg/m'). 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 pg/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. Cancer 1996; 72441-51. 0 I996 American Cancer Society.