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Methadone for Cancer Pain Management in Children: A Review of Literature

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Abstract

Pain associated with cancer is a common feature among children and adolescents. Among opioids, methadone is a unique drug for its multiple mechanisms of action. Methadone is currently underutilized in children. The use of methadone for cancer pain management in children was assessed in a systematic review. Altogether, 141 children receiving methadone were examined, and another 126 children were assessed for QT prolongation. In the clinical studies, modalities of use, dosing, and duration of assessment were highly variable. In general, methadone was effective and well tolerated with a limited tendency for dose increases. QT prolongation was reported in a percentage of patients independently of the dosages or other variables. The majority of studies considered the use of methadone to be safe and effective in children. Despite methadone possessing interesting properties that make this drug unique in a pediatric context, data is limited, and the literature available is based on retrospective studies. Methadone could be an effective, inexpensive, and versatile medication in children with cancer who have pain. This drug deserves more interest and should prompt studies of better quality with a larger number of patients.

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References

  1. Steliarova-Foucher E, Colombet M, Ries LAG, et al. International incidence of childhood cancer, 2001–10: a population-based registry study. Lancet Oncol. 2017;18:719–71.

    Article  PubMed  PubMed Central  Google Scholar 

  2. World Health Organization (2021) CureAll framework: WHO global initiative for childhood cancer: increasing access, advancing quality, saving lives. World Health Organization. https://apps.who.int/iris/handle/10665/347370.

  3. Lam CG, Howard SC, Bouffet E, Pritchard-Jones K. Science and health for all children with cancer. Science. 2019;363(6432):1182–6.

    Article  CAS  PubMed  Google Scholar 

  4. World Health Organization (2020) Assessing national capacity for the prevention and control of noncommunicable diseases: report of the 2019 global survey. World Health Organization. https://apps.who.int/iris/handle/10665/331452

  5. WHO 2012 World Health Organization. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. apps.who.int/iris/bitstream/10665/44540/1/9789241548120_Guidelines.pdf

  6. Wiffen PJ, Cooper TE, Anderson AK, et al. Opioids for cancer-related pain in children and adolescents. Cochrane Database Syst Rev. 2017;7(7):CD012564.

    PubMed  Google Scholar 

  7. Edmonds KP, Saunders IM, Willeford A, Ajaji TA, Atayee RS. Emerging challenges to the safe and effective use of methadone for cancer-related pain in paediatric and adult patient populations. Drugs. 2020;80:115–30.

    Article  PubMed  Google Scholar 

  8. Habashy C, Springer E, Hall EA, Anghelescu DL. Methadone for pain management in children with cancer. Paediatr Drugs. 2018;20:409–16.

    Article  PubMed  Google Scholar 

  9. Ebert B, Andersen S, Krogsgaard-Larsen P. Ketobemidone, methadone and pethidine are non-competitive N-methyl-d-aspartate (NMDA) antagonists in the rat cortex and spinal cord. Neurosci Lett. 1995;187:165–8.

    Article  CAS  PubMed  Google Scholar 

  10. Gorman AL, Elliott KJ, Inturrisi CE. The d- and l-isomers of methadone bind to the non-competitive site on the N-methyld- aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett. 1997;223:5–8.

    Article  CAS  PubMed  Google Scholar 

  11. Vyklicky V, Korinek M, Smejkalova T, Balik A, Krausova B, Kaniakova M, et al. Structure, function, and pharmacology of NMDA receptor channels. Physiol Res. 2014;63(Suppl 1):S191-203.

    Article  CAS  PubMed  Google Scholar 

  12. Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science. 1991;251:85–7.

    Article  CAS  PubMed  Google Scholar 

  13. Price DD, Mayer DJ, Mao J, Caruso FS. NMDA-receptor antagonists and opioid receptor interactions as related to analgesia and tolerance. J Pain Symptom Manag. 2000;19(1 Suppl):S7-11.

    Article  CAS  Google Scholar 

  14. Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-d-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999;289:1048–53.

    CAS  PubMed  Google Scholar 

  15. Dinis-Oliveira RJ. Metabolomics of methadone: clinical and forensic toxicological implications and variability of dose response. Drug Metab Rev. 2016;48:568–76.

    Article  CAS  PubMed  Google Scholar 

  16. Beuken-van Everdingen MJH, Geurts JW, Patijn J. Prolonged QT interval by methadone: relevance for daily practice. J Opioid Manage. 2013;9:263–7.

    Article  Google Scholar 

  17. Madden K, Liu D. Bruera E Attitudes, beliefs, and practices of pediatric palliative care physicians regarding the use of methadone in children with advanced cancer. J Pain Symptom Manage. 2019;57:260–5.

    Article  PubMed  Google Scholar 

  18. Roth M, Davies D, Friebert S, Wang D, Kim M, Zelcer S. Attitudes and practices of pediatric oncologists regarding methadone use in the treatment of cancer-related pain: results of a North American Survey. J Pediatr Hematol Oncol. 2013;35:103–7.

    Article  CAS  PubMed  Google Scholar 

  19. http://www.prisma-statement.org/PRISMAStatement/Checklist.aspx

  20. Anghelescu DL, Faughnan LG, Hankins GM, Ward DA, Oakes LL. Methadone use in children and young adults at a cancer center: a retrospective study. J Opioid Manag. 2011;7:353–61.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Davies D, DeVlaming D, Haines C. Methadone analgesia for children with advanced cancer. Pediatr Blood Cancer. 2008;51:393–7.

    Article  PubMed  Google Scholar 

  22. Hall EA, Sauer HE, Habashy C, Anghelescu DL. Methadone for cancer pain in pediatric end-of-life care. Am J Hosp Palliat Med. 2021;38:914–9.

    Article  Google Scholar 

  23. Madden K, Milla S, Dibaj S, Williams JL, Liu D, Bruera E. Methadone as the initial long-acting opioid in children with advanced cancer. J Palliat Med. 2018;21:1317–21.

    Article  PubMed  Google Scholar 

  24. Palat G, Algotsson C, Rayala S, Haridass V, Nethagani J, Rapelli V, Medhin MG, Brun E, Segerlantz M. The use of methadone in pediatric cancer pain—a retrospective study from a governmental cancer center in India. Indian J Palliat Care. 2021;27:133–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mott C, Sarpal A, Moss K, Herbetr A. Methadone for analgesia in children with life-limiting illness: experience from a tertiary children’s health service. Children (Basel). 2018;5:86.

    PubMed  PubMed Central  Google Scholar 

  26. Anghelescu DL, Patel RM, Mahoney DP, Trujillo L, Faughnan LG, Steen BD, Baker JN. Methadone prolongs cardiac conduction in young patients with cancer-related pain. J Opioid Manag. 2016;12:131–8.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Madden K, Park M, Liu D, Bruera E. The frequency of QTc prolongation among pediatric and young adult patients receiving methadone for cancer pain. Pediatr Blood Cancer. 2017;64(11).

  28. Madden K, Jo E, Williams JL, Liu D, Bruera E. Corrected QT interval prolongation in pediatric and young adult patients on methadone for cancer-related pain. J Pain Symptom Manage. 2019;58:678–84.

    Article  PubMed  Google Scholar 

  29. Piccinini JA, Killinger JS, Hammad HT, Gerber LM, Dayton JD. QT interval prolongation in the pediatric oncologic population on methadone. J Pediatr Hematol Oncol. 2020;42:e121–4.

    Article  Google Scholar 

  30. Zernikow B, Smale H, Michel E, et al. Paediatric cancer pain management using the WHO analgesic ladder–results of a prospective analysis from 2265 treatment days during a quality improvement study. Eur J Pain. 2006;10:587–95.

    Article  PubMed  Google Scholar 

  31. Zernikow B, Michel E, Craig F, Anderson BJ. Pediatric palliative care: use of opioids for the management of pain reported. Paediatr Drugs. 2009;11:129–51.

    Article  PubMed  Google Scholar 

  32. McPherson ML, Walker KA, Davis M, et al. Safe and appropriate use of methadone in hospice and palliative care: expert consensus white paper. J Pain Symptom Manage. 2019;57:635–45.

    Article  PubMed  Google Scholar 

  33. Di Sarno L, Gatto A, Korn D. Pain management in pediatric age. An update. Acta Biomed. 2023;94: e2023174.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Banerjiee S, Butcher R. Pharmacological interventions for chronic pain in pediatric patients: a review of guidelines. Ottawa: CADTH; 2020.

    Google Scholar 

  35. Mercadante S, Bruera E. Opioid switching in cancer pain: from the beginning to nowadays. Crit Rev Oncol Hematol. 2016;99:241–8.

    Article  PubMed  Google Scholar 

  36. Mercadante S, Adile C, Ferrera P, Pallotti MC, Ricci M, Bonanno G, Casuccio A. Methadone as first-line opioid for the management of cancer pain. Oncologist. 2022;27:323–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Palat G, Chary S. Practical guide for using methadone in pain and palliative care practice. Indian J Palliat Care. 2018;24(Suppl 1):S21–9.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Sebastiano Mercadante.

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Mercadante, S. Methadone for Cancer Pain Management in Children: A Review of Literature. Drugs 84, 203–208 (2024). https://doi.org/10.1007/s40265-024-02001-y

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