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. 2024 Dec 17:17:4187-4196.
doi: 10.2147/JPR.S488416. eCollection 2024.

Catalyzing Pharmacogenomic Analysis for Informing Pain Treatment (C-PAIN): A Randomized Trial of Preemptive CYP2D6 Genotyping in Cancer Palliative Care

Youngwoo Cho  1 , Theodore Karrison  2 , Matthew M Jack  3 , Anish R Choksi  3   4 , Randall W Knoebel  3   4 , Kiang-Teck J Yeo  1   5 , Samuel L Volchenboum  6 , Russell Z Szmulewitz  1   7 , Everett E Vokes  7 , Mark J Ratain  1   3   7 , Peter H O'Donnell  1   3   7
Affiliations

Catalyzing Pharmacogenomic Analysis for Informing Pain Treatment (C-PAIN): A Randomized Trial of Preemptive CYP2D6 Genotyping in Cancer Palliative Care

Youngwoo Cho et al. J Pain Res. .

Abstract

Background: Cancer patients frequently suffer from pain, often managed with opioids. However, undertreated pain remains a significant concern. Opioid effectiveness varies due to genetic differences in how individuals metabolize some of these medications. While prior research suggests promise in tailoring opioid prescriptions based on CYP2D6 genetic makeup, its application in cancer pain management remains limited. This study investigates the potential benefits of preemptive CYP2D6 genotyping for cancer patients initiating opioid therapy, focusing on codeine, tramadol, and hydrocodone, whose efficacy is demonstrably impacted by CYP2D6 variations.

Methods: This is a randomized, prospective study to evaluate the effects of preemptive pharmacogenomic (PGx) testing on opioid dosing decisions/selections and composite pain score in oncology patients. Patients with metastatic solid tumors for whom near-future opioid therapy is anticipated will be randomized to PGx and control arms, stratified by the presence or absence of bony metastases and history of opioid use. In the PGx arm, patients will be preemptively tested using a panel of pharmacogenomic genetic variants, and providers will receive opioid dosing guidance via an electronic medical record-embedded clinical decision support tool. In the control arm, pain prescribing will occur per standard of care without genotype information.

Planned outcome: The primary study outcome will be composite pain intensity during the first 45 days after an index opioid prescription for codeine, tramadol, or hydrocodone. Safety will be assessed by comparing opioid-related adverse event rates between the two study arms. Secondary outcomes will include rates of hospitalization/emergency room visits, cumulative morphine equivalents received, and type of first opioid prescribed.

Keywords: CYP2D6; codeine; genetic testing; hydrocodone; pain score; pharmacogenomics; tramadol.

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Conflict of interest statement

Dr Russell Szmulewitz reports grants from Bayer, grants from Pfizer, personal fees from Novartis, outside the submitted work. Dr Everett Vokes reports personal fees from AbbVie, personal fees, non-financial support from AstraZeneca, personal fees from BioNTech, outside the submitted work. Dr Mark Ratain reports grants from National Institutes of Health, during the conduct of the study. Dr Peter O’Donnell reports grants from National Institutes of Health, during the conduct of the study; personal fees from National Institutes of Health, personal fees from O’Brien and Ryan LLP, personal fees from ISMIE, outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study Schema for the C-PAIN Trial. Design of this prospective pharmacogenomics clinical trial, including patient allocation to pharmacogenomic (PGx) and control arms, and primary and secondary endpoints of the study.
Figure 2
Figure 2
Representative Pharmacogenomic Clinical Decision Support (CDS) Summary. Structure and key components of a representative pharmacogenomic clinical decision support summary that will be delivered to treating providers via the electronic medical record within prescribing workflows to inform opioid selection during the trial.
See this image and copyright information in PMC

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