Send to

Choose Destination
Br J Clin Pharmacol. 2016 Jan;81(1):124-30. doi: 10.1111/bcp.12790. Epub 2015 Nov 28.

Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-FU in patients with digestive cancer.

Author information

Laboratoire de Pharmacocinétique La Timone University Hospital of Marseille, Marseille.
Digestive Oncology Unit, La Timone University Hospital of Marseille, Marseille.
Oncopharmacology Unit, Centre Antoine Lacassagne, Nice.
SMARTc Unit, U911 Cro2 Aix-Marseille Univ., Marseille, France.



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.


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 < 0.003, t-test).


Despite this marked reduction in 5-FU dosing, similar efficacy was achieved in the two subsets (clinical benefit: 40 vs. 43%, stable disease: 40 vs. 37%, progressive disease: 20% in both subsets, P = 0.893, Pearson's chi-square). No difference in toxicities was observed (P = 0.104, Fisher's exact test). Overall, only 3% of early severe toxicities were recorded, a value markedly lower than the 15-30% ones usually reported with 5-FU.


This feasibility study shows how simplified DPD-based adaptive dosing of 5-FU can reduce sharply the incidence of treatment-related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology.


5-FU; DPD deficency; adaptive dosing; digestive oncology; efficacy; toxicity

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center