In the treatment of tumor diseases, pharmacogenetic tests are used to identify patients patients who have a high risk of severe side effects from certain chemotherapeutic agents. Depending on the genetic constellation, the dosage can be adjusted or an alternative drug can be used. The test results also provide valuable information for psycho-oncological and pain therapy medication decisions.
In the treatment of tumor diseases, active substances are used that can be associated with severe toxic side effects. A pharmacogenetic test makes it possible to identify patients which have a high risk of reacting to certain chemotherapeutic agents with severe side effects. This makes it possible to adjust the dosage individually depending on the genetic constellation or to avoid the drug if necessary.
Oncological patients patients often take other medications due to their disease, such as antidepressants, analgesics and proton pump inhibitors. A pharmacogenetic test can provide valuable information about the efficacy or the risk of serious adverse drug reactions.
Chemotherapeutic agents frequently used for solid tumors are 5-FU and capecitabine. These are broken down by the enzyme dihydropyrimidine dehydrogenase (DPD). In around 4.5 to 5% of patients , variants in the DPYD gene lead to reduced activity of the DPD enzyme and thus to the occurrence of toxic side effects at the usual dosage. In around 0.3% of patients , genetic variants lead to a complete loss of enzyme activity and thus to very severe to fatal toxic side effects when administering 5-FU or capecitabine. Knowledge of the presence of variants in the DPYD gene makes it possible to adjust the dose of 5-FU or capecitabine or, if necessary, to choose a different chemotherapy.
How does genetics influence the efficacy of concomitant medication, using antidepressants as an example?
The antidepressants of the classes SSRI (serotonin reuptake inhibitors; e.g., sertraline, paroxetine) and TCA (tricyclic antidepressants; e.g., amitriptyline) are metabolized by the enzymes CYP2D6 and/or CYP2C19. Decreased enzyme activity may result in delayed degradation of the drug, which in turn may result in increased concentration at a standard recommended dose and the occurrence of adverse drug reactions. In the case of increased enzyme activity, on the other hand, a faster degradation of the drug at a standard dosage may result in an insufficient level of effect and the drug effect may not be achieved.
Likewise, genetics influences the effect or risk of adverse drug reactions with analgesics such as codeine and tramadol from the opioid group, or NSAIDs and the proton pump inhibitors (PPIs, gastric acid blockers) often prescribed together with NSAIDs.
