What enzyme deficiency can lead to severe toxicity in patients treated with 5-fluorouracil (5FU)?

The enzyme deficiency that can lead to severe toxicity in patients treated with 5-fluorouracil (5FU) is related to dihydropyrimidine dehydrogenase (DPD). DPD is a critical enzyme in the catabolism of pyrimidine analogs, including 5FU. It is responsible for the conversion of 5FU into inactive metabolites. When there is a deficiency of DPD, the clearance of 5FU is significantly impaired, leading to elevated levels of the drug in the patient's system. This accumulation can cause serious and potentially life-threatening toxicities, such as gastrointestinal and hematologic toxic effects.

Understanding the role of DPD is essential in the context of chemotherapy because testing for DPD deficiency can help identify patients who are at risk for severe adverse effects from 5FU treatment, allowing for dose adjustments or alternative therapies to be considered. Such precautionary measures are crucial in oncology practice to minimize complications and enhance treatment efficacy.