Chemotherapy has long been a crucial treatment for patients with cancer, but recent studies have revealed a potential danger for a small percentage of individuals who carry a genetic change in a gene called DPYD. This genetic variation can make certain chemotherapy medications, such as fluorouracil (5-FU) and capecitabine (Xeloda or CAPE), toxic or even fatal.
Research suggests that individuals with one variant in the DPYD gene have a significantly higher risk of treatment-related fatality if they take these drugs, with the risk being 25 times higher than the average person. For those with two variants in the gene, exposure to these medications can be deadly, highlighting the importance of genetic testing before starting chemotherapy.
In the UK and European Union, pre-treatment DPYD testing has been recommended since 2020, with patients carrying one variant receiving a lower initial dose to monitor their response. However, in the United States, the FDA has only recently issued warnings about the need for genetic testing before prescribing these medications.
Despite the potential benefits of genetic testing, there are challenges and barriers to its widespread adoption. The complexity of genetic variations in the DPYD gene, the rapid evolution of genetic testing technology, and the lack of recognition and reimbursement for genetic counselors and pharmacists specializing in pharmacogenetics are all factors contributing to the reluctance of some clinicians to offer testing.
However, studies have shown that implementing pre-treatment DPYD genetic testing can be cost-effective and significantly reduce adverse events in cancer care. Clinical decision support tools for pharmacogenetics are available to guide clinicians in using genetic testing effectively.
Overall, while genetic testing for medication response may present challenges, it has the potential to significantly improve the safety and effectiveness of chemotherapy for cancer patients. Patients and their healthcare teams are encouraged to discuss the possibility of genetic testing before starting treatment to ensure the best possible outcomes.