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Abstract
Identifying polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) genes is gaining importance as predictors of fluoropyrimidine-associated toxicity. The recommendation of dose adjustment for chemotherapy guided by the presence of polymorphisms of the DPYD gene can potentially improve treatment safety for a large number of patients, saving lives, avoiding complications and reducing health care costs. This article discusses how personalisation of fluoropyrimidine treatment based on the identification of DPYD variants can mitigate toxicities and be cost effective.
Highlights
Fluoropyrimidines are one of the most widely used chemotherapy drugs against solid cancers, either as monotherapy or in combination therapy, and more than 2 million cancer patients are exposed annually to this drug, which includes 5-fluorouracil (5-FU) and its oral pro-drugs capecitabine and tegafur [1]
In patients with certain enzyme deficiencies that act on the fluoropyrimidine metabolism, the use of these chemotherapeutic agents can lead to life-threatening complications, including severe nausea, vomiting and diarrhoea with volume depletion, extensive skin and mucositis changes, pancytopenia with risk of bleeding and infection, cardiotoxicity and neurological abnormalities such as cerebellar ataxia, cognitive dysfunction and altered level of consciousness [5,6,7,8,9,10,11,12,13]
There is one copy of a decreased function allele and one copy of a no function allele of the dihydropyrimidine dehydrogenase (DPYD) gene. This patient may be at risk for adverse drug reactions to medications that are metabolised by dihydropyrimidine dehydrogenase (DPD) and a dose adjustment or alternative therapeutic agents to fluoropyrimidine may be indicated
Summary
Fluoropyrimidines are one of the most widely used chemotherapy drugs against solid cancers, either as monotherapy or in combination therapy, and more than 2 million cancer patients are exposed annually to this drug, which includes 5-fluorouracil (5-FU) and its oral pro-drugs capecitabine and tegafur [1]. There is an overlap of toxicities between chemotherapeutic agents, which can increase the risk of adverse effects, as well as drug interactions that directly affect the metabolism of 5-FU, modifying the risk profile for DPYD variants Another aspect is the sequencing of therapy on DPD function, for example, prior use of gemcitabine can induce liver tissue damage and severe toxicity with capecitabine even in the absence of DPD dysfunction. There is one copy of a decreased function allele and one copy of a no function allele of the DPYD gene This patient may be at risk for adverse drug reactions to medications that are metabolised by DPD and a dose adjustment or alternative therapeutic agents to fluoropyrimidine may be indicated. AIncidence by 100.000 habitants – Inca 2020 [49, 50] b5-year prevalence – Globocan 2020 [51]
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