1. Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-FU in patients with digestive cancer
- Author
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Muriel Duluc, Gérard Milano, Manon Duval, Anne Rodallec, Bruno Lacarelle, Laetitia Dahan, Joseph Ciccolini, Jean-François Seitz, and Manon Launay
- Subjects
Pharmacology ,medicine.medical_specialty ,business.industry ,Cancer ,medicine.disease ,030226 pharmacology & pharmacy ,Gastroenterology ,03 medical and health sciences ,Exact test ,Dihydropyrimidine dehydrogenase deficiency ,0302 clinical medicine ,Fluorouracil ,030220 oncology & carcinogenesis ,Internal medicine ,Dihydropyrimidine dehydrogenase ,medicine ,Pharmacology (medical) ,Dosing ,business ,Pharmacogenetics ,Progressive disease ,medicine.drug - Abstract
Aims 5-FU is the backbone of most regimens in digestive oncology. Administration of standard 5-FU leads to 15–30% of severe side effects, and lethal toxicities are regularly reported with fluoropyrimidine drugs. Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome responsible for most cases of life-threatening toxicities upon 5-FU intake, and pre-treatment checking for DPD status should help to reduce both incidence and severity of side effects through adaptive dosing strategies. Methods We have used a simple method for rapidly establishing the DPD phenotype of patients with cancer and used it prospectively in 59 routine patients treated with 5-FU-based therapy for digestive cancers. No patient with total DPD deficiency was found but 23% of patients exhibited poor metabolizer phenotype, and one patient was phenotyped as profoundly deficient. Consequently, 5-FU doses in poor metabolizer patients were cut by an average 35% as compared with non deficient patients (2390 ± 1225 mg vs. 3653 ± 1371 mg, P
- Published
- 2015
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