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The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer

The Pharmacogenomics Journal volume 8, pages 256–267 (2008)Cite this article

Abstract

The purpose of this study was to determine simple genetic factors helpful to tailor 5-FU administration and determine strategy in first-line chemotherapy of advanced colorectal cancer. In 76 patients initially treated by 5-FU, thymidylate synthase, dihydropyrimidine dehydrogenase and methylene tetrahydrofolate reductase germinal polymorphisms, dihydrouracil/uracil plasma ratio and 5-FU plasma clearance were investigated and correlated for tolerance (10.5% grade 3 and 4 toxicity) and efficacy (32.9% objective response rate and 20 months median overall survival time). Toxicity was linked to performance status >2 (P=0.004), low UH2/U ratio, 2846 A>T, IVS 14+1G>A for DPD (P=0.031), and homozygoty C/C for MTHFR 1298 A>C (P=0.0018). The overall survival of the patients with a 3R/3R TS genotype associated with C/C for 677 C>T or A/A for 1298 A>C was statistically shorter (log-rank test P=0.0065). Genetic factors permit the tailoring of 5-FU treatment. They should occupy center stage in future clinical trials for specifically designing treatment for patients with a given biologic feature.

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Acknowledgements

We would like to thank the Comité Départemental du Maine et Loire de la Ligue Contre Le Cancer and the Rotary club of Angers for their financial support.

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Authors and Affiliations

  1. Department of Medical Oncology and Clinical Pharmacology, INSERM U564 Centre Paul Papin, Centre Régional de Lutte Contre le Cancer, Angers, Cedex, France

    O Capitain, M Boisdron-Celle, A-L Poirier, S Abadie-Lacourtoisie, A Morel & E Gamelin

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  1. O Capitain
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Correspondence to E Gamelin.

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Capitain, O., Boisdron-Celle, M., Poirier, AL. et al. The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. Pharmacogenomics J 8, 256–267 (2008). https://doi.org/10.1038/sj.tpj.6500476

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