Abstract

Purpose: Individual genetic variation can affect both pain expression and opioid response. Large cohort datasets are required to validate evidence influencing genomic factors in opioid response. This study examined the feasibility of establishing an opioid pharmacogenomics registry for cancer patients containing longitudinal matched clinical, symptom, pharmacological, and genomic data, with an a priori feasibility target of 50 participants within 12 months.
Methods: Consecutive patients with advanced cancer receiving opioids across five palliative care services were recruited. Clinical data (demographics, pain data, adverse effects, medications) and blood (DNA, RNA, pharmacokinetics) were collected over two time points. Patient and clinician qualitative interviews were conducted to assess acceptability. This study was approved by the SVHA Ethics Committee, Melbourne, Australia (HREC 252/18).
Results: Enrollment for the registry was deemed feasible. Fifty-eight participants were recruited (median age 63.7, 45% female, 83% complete data), with the most frequent diagnosis being lung cancer (n = 18, 33%) and oxycodone the most frequently prescribed opioid (n = 30, 52%). Qualitative data indicated positive engagement from both patients and clinicians.
Conclusion: Establishing a longitudinal opioid pharmacogenomic registry in patients with cancer receiving palliative care is feasible and readily acceptable.

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References

1. van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, et al. Update on prevalence of pain in patients with cancer: Systematic review and meta-analysis. J Pain Symptom Manage 2016;51(6):1070.e9–1090.e9.
2. Meñaca A, Evans N, Andrew E, et al. End-of-life care across Southern Europe: A critical review of cultural similarities and differences between Italy, Spain and Portugal. Crit Rev Oncol Hematol 2012;82(3):387–401.
3. Wiffen PJ, Bee W, Derry S, et al. Opioids for cancer pain—An overview of Cochrane reviews. Cochrane Database Syst Rev 2017;7(7):Cd012592.
4. Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: Evidence-based recommendations from the EAPC. European Palliative Care Research Collaborative (EPCRC); European Association for Palliative Care (EAPC). Lancet Oncol 2012;13(2):e58–e68.
5. Mercadante S, Bruera E. Opioid switching: A systematic and critical review. Cancer Treat Rev 2006;32(4):304–315.
6. Whirl-Carrillo M, Huddart, R, Gong L, et al. An evidence-based framework for evaluating pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2021;110(3):563–572.
7. Crews K, Monte AA, Huddart R, et al. Clinical pharmacogenetics implementation consortium guideline for CYP2D6, OPRM1, and COMT genotypes and select opioid therapy. Clin Pharmacol Ther 2021;110(4):888–896.
8. Bugada D, Lorini LF, Fumagalli R, et al. Genetics and opioids: Towards more appropriate prescription in cancer pain. Cancers (Basel) 2020;12(7):1951.
9. Cox B. Recent developments in the study of opioid receptors. Mol Pharmacol 2013;83(4):723–728.
10. Droney J, Riley J. Opioid genetics in the context of opioid switching. Curr Opin Support Palliat Care 2012;6(1):10–16.
11. Knudsen AK, Brunelli C, Kaasa S, et al. Which variables are associated with pain intensity and treatment response in advanced cancer patients?—Implications for a future classification system for cancer pain. Eur J Pain 2011;15(3):320–327.
12. Branford R, Droney J, Ross JR. Opioid genetics: The key to personalized pain control? Clin Genet 2012;82(4):301–310.
13. Laugsand E, Skorpen F, Klepstad P. Genetic and non-genetic factors associated with constipation in cancer patients receiving opioids. Clin Transl Gastroenterol 2015;6:e90.
14. Klepstad P, Flatvad T, Skorpen F, et al. Influence from genetic variability on opioid use for cancer pain: A European Genetic Association Study of 2294 Cancer Pain Patients. Pain 2011;152(5):1139–1145.
15. Barratt D, Klepstad P, Dale O, et al. Innate immune signalling genetics of pain, cognitive dysfunction and sickness symptoms in cancer pain patients treated with transdermal fentanyl. PLoS One 2015;10(9):e0137179.
16. Clinical Pharmacogenomics Implementation Consortium 2021. Genes-Drugs. 22 May 2021. Available from: https://cpicpgx.org/genes-drugs/ [Last accessed December 4, 2022].
17. Olesen A, Gronlund D, Gram M, et al. Prediction of opioid dose in cancer pain patients using genetic profiling: Not yet an option with support vector machine learning. BMC Res Notes 2018;11(1):78.
18. Klepstad P, Skorpen F. Genetic findings related to pain and analgesics-why are they so inconsistent? Pain 2016;157(2):284–285.
19. Abernethy A, Shelby-James T, Fazekas BS, et al. The Australia-modified Karnofsky Performance Status (AKPS) scale: A revised scale for contemporary palliative care clinical practice [ISRCTN81117481]. BMC Palliat Care 2005;4:4.
20. Bennett M. The LANSS Pain Scale: The Leeds assessment of neuropathic symptoms and signs. Pain 2001;92(1–2):147–157.
21. Mendoza T, Mayne T, Rublee D, et al. Reliability and validity of a modified Brief Pain Inventory short form in patients with osteoarthritis. Eur J Pain 2006;10(4):353–361.
22. Nekolaichuk C, Fainsinger RL, Aass N, et al. European Palliative Care Research Collaborative (EPCRC). The Edmonton Classification System for Cancer Pain: Comparison of pain classification features and pain intensity across diverse palliative care settings in eight countries. J Palliat Med 2013;16(5):516–523.
23. Sperlinga R, Campagna S, Berruti A, et al. Alberta Breakthrough Pain Assessment Tool: A validation multicentre study in cancer patients with breakthrough pain. Eur J Pain 2015;19(7):881–888.
24. Gaudreau J, Gagnon P, Harel F, et al. Fast, systematic and continuous delirium assessment in hospitalised patients: The Nursing Delirium Screening Scale. J Pain Symptom Manag 2005;29(4):368–375.
25. Breitbart W, Rosenfeld B, Roth A, et al. The Memorial Delirium Assessment Scale. J Pain Symptom Manage 1997;13(3):128–137.
26. Hui D, Bruera E. The Edmonton Symptom Assessment System 25 years later: Past, present and future developments. J Pain Symptom Manage 2017;53(3):630–643.
27. Guy W. ECDEU Assessment for Psychopharmacology. US Department of Health, Education and Welfare: Rockville, MD, USA; 1976.
28. NHMRC, National Statement on Ethical Conduct in Human Research 2007 (Updated 2018). The National Health and Medical Research Council, Editor. Commonwealth of Australia: Canberra, Australia; 2018.
29. Proctor E, Silmere H, Raghavan R, et al. Outcomes for implementation research: Conceptual distinctions, measurement challenges, and research agenda. Adm Policy Ment Health 2011;38(2):65–76.
30. Kalpakidou AK, Todd C, Omar R, et al. Study recruitment factors in advanced cancer: The Prognosis in Palliative care Study II (PiPS2)—A multicentre, prospective, observational cohort project. BMJ Support Palliat Care 2021:p. bmjspcare-2020-002670.
31. Stone P, Gwilliam B, Keeley V, et al. Factors affecting recruitment to an observational multicentre palliative care study BMJ Support Palliat 2013;3:318–323.
32. Hui D, Glitza I, Chisholm G, et al. Attrition rates, reasons, and predictive factors in supportive care and palliative oncology clinical trials. Cancer 2013;119:1098–1105.
33. White C, Hardy J. What do palliative care patients and their relatives think about research in palliative care? A systematic review. Support Care Cancer 2010;18:905–911.

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cover image Journal of Palliative Medicine
Journal of Palliative Medicine
Volume 26Issue Number 3March 2023
Pages: 411 - 417
PubMed: 36493378

History

Published in print: March 2023
Published online: 1 March 2023
Published ahead of print: 9 December 2022
Accepted: 2 November 2022

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Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Peter MacCallum Cancer Centre, Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Peter MacCallum Cancer Centre, Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Palliative Care Service, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Peter MacCallum Cancer Centre, Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Discipline of Pharmacology, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Fitzroy, Victoria, Australia.
Department Intensive Care Medicine, St. Olavs University Hospital, Trondheim, Norway.
Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
Personalised Oncology Division, Walter Eliza Hall Institute, University of Melbourne, Fitzroy, Victoria, Australia.
Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Peter MacCallum Cancer Centre, Melbourne, Fitzroy, Victoria, Australia.
Palliative Care Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Notes

Address correspondence to: Jennifer Philip, PhD, MMed, MBBS, Department of Medicine, University of Melbourne, Fitzroy 3065, Victoria, Australia [email protected]

Authors' Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by J.P., A.W., L.P., and B.L. The first draft of the article was written by J.P., and all authors commented on previous versions of the article. All authors read and approved the final article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was supported by peer-reviewed philanthropic grants from Research Endowment Fund, St Vincent's Hospital, Melbourne, the Bethlehem Griffiths Research Foundation, and the Australian and New Zealand College of Anaesthetists (Russell Cole Memorial Research Award).

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Informed consent was obtained from all individual participants included in the study.

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