Design and rational for the precision medicine guided treatment for cancer pain pragmatic clinical trial - PubMed
doi: 10.1016/j.cct.2018.03.001. Epub 2018 Mar 10.
J Kevin Hicks 2 , Diane G Portman 3 , Kristine A Donovan 3 , Priya Gopalan 4 , Jessica Schmit 4 , Jason Starr 4 , Natalie Silver 5 , Yan Gong 1 , Taimour Langaee 1 , Michael Clare-Salzler 6 , Petr Starostik 7 , Young D Chang 3 , Sahana Rajasekhara 3 , Joshua E Smith 3 , Heloisa P Soares 8 , Thomas J George Jr 4 , Howard L McLeod 2 , Larisa H Cavallari 9
Affiliations
- PMID: 29535047
- PMCID: PMC5899651
- DOI: 10.1016/j.cct.2018.03.001
Design and rational for the precision medicine guided treatment for cancer pain pragmatic clinical trial
Scott A Mosley et al. Contemp Clin Trials. 2018 May.
Abstract
Introduction: Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of pain management. Opioid therapy is empirically selected, and patients often require adjustments in therapy to effectively alleviate pain or ameliorate adverse drug effects that interfere with quality of life. There are data suggesting CYP2D6 genotype may contribute to inter-patient variability in response to opioids through its effects on opioid metabolism. Therefore, we aim to determine if CYP2D6 genotype-guided opioid prescribing results in greater reductions in pain and symptom severity and interference with daily living compared to a conventional prescribing approach in patients with cancer.
Methods: Patients with solid tumors with metastasis and a self-reported pain score ≥ 4/10 are eligible for enrollment and randomized to a genotype-guided or conventional pain management strategy. For patients in the genotype-guided arm, CYP2D6 genotype information is integrated into opioid prescribing decisions. Patients are asked to complete questionnaires regarding their pain, symptoms, and quality of life at baseline and 2, 4, 6, and 8 weeks after enrollment. The primary endpoint is differential change in pain severity by treatment strategy (genotype-guided versus conventional pain management). Secondary endpoints include change in pain and symptom interference with daily living.
Conclusion: Pharmacogenetic-guided opioid selection for cancer pain management has potential clinical utility, but current evidence is limited to retrospective and observational studies. Precision Medicine Guided Treatment for Cancer Pain is a pragmatic clinical trial that seeks to determine the utility of CYP2D6 genotype-guided opioid prescribing in patients with cancer.
Trial registration: ClinicalTrials.gov NCT02664350.
Keywords: CYP2D6; Cancer; Genotype; Opioid; Oxycodone; Pain; Patient reported outcome; Pharmacogenetic; Symptom; Trial design.
Copyright © 2018 Elsevier Inc. All rights reserved.
Figures

Study design flow chart. BPI-SF: Brief Pain Inventory-Short Form; MDASI: MD Anderson Symptom Inventory; EMR: Electronic Medical Record

Example of a consult note based on CYP2D6 genotype which is uploaded into the patients EMR.

Quick-reference clinical decision tool to assist physicians in interpreting genotype results.

Timeline of self-reported pain scores by a patient with the IM phenotype, randomized to the genotype-guided arm.
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