Pharmacogenomics has revolutionized medication therapy, especially in oncology. Specifically, monoclonal antibodies (MAbs) have shown benefit when combined with pharmacogenomics. These positive developments are marred, however, by significant adverse events with MAbs and certain targets such as HER2 for trastuzumab, epidermal grown factor receptor for cetuximab, and anti-CD20 for rituximab. Developing MAb therapeutics is largely dependent on finding biomarkers and relevant polymorphisms. For oncology research, pharmacogenomics help predict cancer susceptibility, tumor progression and recurrence, patient survival, and response and toxicity to chemotherapy.
Toxicity to chemotherapy can be predicted largely by genetic polymorphisms. In a small study of 56 patients who received trastuzumab, it was shown that five patients who developed cardiotoxicity from trastuzumab had the HER2-655Val/Ile phenotype. More studies would need to be done to confirm this, but if proven accurate, this is just one example of how pharmacogenomics may help guide treatment. Responses to MAbs can be affected by variations in expression of any element.
Importantly, pharmacogenomics can help pharmacists guide supportive care for adverse effects such as nausea and vomiting, pain, depression, neuropathy, and infections in patients receiving chemotherapy. Suboptimal management of supportive-care symptoms plays a big role in patients’ response to therapy and requires additional research. If pharmacogenomics can predict response to chemotherapy and side effects, then pharmacists can contribute individualized treatment plans.
Chemotherapy-induced nausea and vomiting is one example. CYP2D6 is a key metabolic pathway for inactivation of 5HT3 antagonists and may degrade the effectiveness of these medications. The only 5HT3 antagonist that does not interact with CYP2D6 is granisetron, which may be the only reasonable option for patients who express more CYP2D6 than other patients. CYP2D6 genetic testing is available currently and can help guide nausea and vomiting treatment choices.
Patients who are poor or ultrarapid medication metabolizers can experience different outcomes. Pain management can be largely dependent on pharmacogenomics as well. Patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid certain opioids, such as codeine, tramadol, hydrocodone, and oxycodone, as they may be at risk for treatment failure. Selection of certain antifungals for chemotherapy prophylaxis can also be guided by pharmacogenomics. Poor and ultrarapid metabolizers of CYP2C19 should avoid the use of voriconazole as primary prophylaxis.
Antidepressants play a big role in managing patients’ depression, insomnia, and hot flashes caused by certain chemotherapy agents. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants are commonly used agents; however, patients who are poor metabolizers or ultrarapid metabolizers of CYP2D6 and CYP2C19 may have a decreased response due to drug interactions. Newer antidepressants such as vortioxetine, levomilnacipran, and vilazodone may be better alternatives for these patients.
The important role of pharmacogenomics in supportive oncology care can help individualize treatment plans and avoid untreated side effects. Oncology care could be revolutionized by integrating medication management and supportive care with pharmacogenomics.
« Click here to return to Hematology & Oncology Update.