Opioids are the most potent analgesics and are used to treat severe pain, specifically pain associated with cancer – a significant factor in reducing quality of life and clinical outcomes in such patients as detailed in Cancer Control “Clinical Implications of Opioid Pharmacogenomics in Patients with Cancer” (October 2015).
Inter-individual Differences in Genetically Modulated Opioid Response
The study reviewed clinical studies involving the pharmacodynamics and pharmacokinetics of opioids. It examined the opioid agents morphine, codeine, tramadol, oxycodone, fentanyl, and hydrocodone and the relationship to single nucleotide polymorphisms (SNPs): OPRM1, COMT (specifically COMT Val Met), CYP2D6, CYP3A4/5, and ABCB1, which the study claimed are responsible for the inter-individual differences in opioid response.
The authors specifically found that OPRM1, COMT Val Met, and ABCB1 are most strongly correlated with morphine response. One study combined OPRM1 and ABCB1 and found that patients with both of these genetic variants were the best responders as indicated in patients’ measures of pain intensity. In another study, patients with OPRM1 and COMT Val Met needed the lowest morphine dose compared to other genotypes. All three together demonstrated no difference in morphine dose requirements.
CYP2D6 Variants Correlate with Drug Efficacy
Similarly, the presence of CYP2D6 variants correlated positively with variations in codeine and tramadol efficacy. CYP2D6 is responsible in converting the analgesic properties of codeine and tramadol. In studies investigating codeine pharmacotherapy in cancer patients, analgesic differences and adverse effects were found for CYP2D6 poor, intermediate, and extensive metabolizers.
The authors concluded CYP2D6 testing helps in finding which patients respond positively to codeine. Studies with tramadol focusing on non-cancer pain populations identified CYP2D6 poor metabolizers as having a decreased analgesic response compared to extensive metabolizers. However, the authors noted there has been no specific study relating to tramadol’s analgesic efficacy in cancer populations, arguing tramadol will likely have decreased clinical benefit in patients who are poor CYP2D6 metabolizers.
Call for Preemptive Genotyping in Clinical Practice
The authors assert that these findings “suggest genotyping patients for some of these genetic variants may help predict responses to pain treatments with good rates of sensitivity and specificity and with greater benefits for patients and decreased health care utilization.” Furthermore, the authors assert that utilizing pharmacogenomics data combined with a preemptive genotyping be a “key element” in guiding treatment decisions for cancer patients.