Service pharmacie, Centre hospitalier régional universitaire de Brest, France, Institut de cancérologie et hématologie, Centre hospitalier régional universitaire de Brest, France
- Key words: 5-fluorouracil, capecitabine, dihydropyrimidine dehydrogenase, chemotherapy, toxicity
- DOI : 10.1684/jpc.2013.0257
- Page(s) : 154-60
- Published in: 2013
5-fluorouracil (5-FU) is the cornerstone of the treatment of digestive cancers. Its catabolism and deactivation mostly depend on dihydropyrimidine dehydrogenase (DPD). Patients with DPD deficiency are at high risk of 5-FU early related side effects. Our objective was to assess the safety of 5-FU in patients with DPD deficiency considering a pharmacokinetic approach by the oncopharmacogenetics laboratory.
Material and methods: we retrospectively analysed the files of patients who had DPD deficiency. DPD deficiency was diagnosed by the oncopharmacogenetics laboratory considering a multiparametric analyse. 5-FU dosage adjustments were also suggested by this laboratory by calculating 5-FU plasma clearance after the first 5-FU infusion. 5-FU dosage suggested by the laboratory and the 5-FU dosage really prescribed were compared for each patient and each chemotherapy cycle. Clinical and biological treatment safety data were collected.
Results: we were able to analyse the files of
11 patients. Patients were mostly treated for colorectal cancers in adjuvant or metastatic situation. 5-FU dosage bolus and continuous infusion were consistent with laboratory suggestions in, respectively, 84% and 53% of cases. Two patients experienced haematological toxicity, respectively grade 3 and grade 4 which lead to permanently stop 5-FU. For those two patients DPD deficiency had not been searched prior to prescribing 5-FU.
Conclusion: this study showed that 5-FU was well tolerated in patients DPD deficiency provided clinicians adjusted 5-FU dosage. Our results showed that a pharmacokinetics approach was useful for preventing 5-FU side effects in patients with DPD deficiency.