Fluoropyrimidines (including 5-fluorouracil and its prodrug capecitabine) can cause serious adverse events related to a dihydropyrimidine dehydrogenase (DPD) deficiency, the enzyme involved in the degradation of 5-FU. This study reports the case of a patient treated with capecitabine at a standard dose (2000mg/m²/day) for a breast cancer relapse. Since she had originally well tolerated 5-FU administered as part of a FEC-100 regimen (500 mg/m² 15 min infusion), she was not considered DPD deficient. However, from the first cycle of treatment, the patient experienced serious adverse events, which were resolved by treatment discontinuation. Phenotypic and genotypic analysis revealed that the patient was partially deficient for DPD due to a DPYD gene mutation and consequently could not properly eliminate the molecule, thus exposing her to an increased risk of toxicity. A dose reduction of 50% allowed the patient to tolerate the treatment. The difference in tolerance between the two chemotherapy protocols (FEC-100 and capecitabine in continuous intake) may be explained by the dose-intensity of 5-FU, which is much higher in continuous treatment with capecitabine, leading to the saturation of DPD.
The case of this patient highlights the importance of evaluating DPD activity by a simple phenotypic testing in all patients who are to receive 5-fluorouracil or capecitabine including those who had already well-tolerated low-dose fluoropyrimidines. It emphasizes that dose reduction should be adapted to the dose-intensity of the regimen: the higher it is, the greater the dose reduction may be (for example in continuous capecitabine intake or FOLFOX/FOLFIRI for 5-FU versus short intravenous infusion of 5-FU).
Discover the published article :
Cancer Chemother Pharmacol. 2021 Feb 15.doi: 10.1007/s00280-021-04233-1. Online ahead of print.
Severe toxicity of capecitabine in a patient with DPD deficiency after a safe FEC-100 experience: why we should test DPD deficiency in all patients before high-dose fluoropyrimidines
Maud Maillard, Audrey Eche-Gass, Mony Ung, Aurélie Brice, Sabrina Marsili, Marion Montastruc, Florent Puisset, Fabienne Thomas
Key words :
- breast cancer
- DPD deficiency
Collaborations and thanks
- Service d’oncologie Médicale de l’Institut Claudius Regaud
- Laboratoire de Pharmacologie de l’Institut Claudius Regaud
- Equipe 14, DIAD Dose-Individualization of Anti-cancer Drugs, CRCT
Redaction of the article : Maud MAILLARD
Team 14 DIAD Dose-Individualization of Anti-cancer Drugs, CRCT
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