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Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study

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Abstract

Objectives

This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and/or to improve the level of pain control in oncologic patients.

Patients and methods

Fifty patients on stable doses of morphine for 1 week were switched to methadone using a “stop–start” strategy and randomized in a double-blind fashion to receive either acetaminophen (750 mg PO every 6 hours) or placebo for a 7-day period. We collected data regarding level of pain, side effects, and quality of life.

Results

Substitution of morphine for methadone resulted in a significant reduction in constipation (p < 0.001) and xerostomia (p = 0.03). There was also an improvement in the numeric pain scale (p = 0.03) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 questionnaire. Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced. At the end of the study, most patients (70.8%, p = 0.001) preferred methadone to morphine.

Conclusions

Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia, allowing for a comfortable dosing regimen. In this scenario, the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone.

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References

  1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376. doi:10.1093/jnci/85.5.365

    Article  CAS  PubMed  Google Scholar 

  2. Benítez-Rosario MA, Feria M, Salinas-Martín A, Martínez-Castillo LP, Martín-Ortega JJ (2004) Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain. Cancer 101(12):2866–2873. doi:10.1002/cncr.20712

    Article  PubMed  Google Scholar 

  3. Berquó ES, Souza JMP, Gotlieb SLD (1981) Bioestatística. EPU, São Paulo

    Google Scholar 

  4. Bruera E, Sweeney C (2002) Methadone use in cancer patients with pain: a review. J Palliat Med 5(1):127–138. doi:10.1089/10966210252785097

    Article  PubMed  Google Scholar 

  5. Bruera E, Watanabe S, Fainsinger RL, Spachynski K, Suarez-Almazor M, Inturrisi C (1995) Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain. Pain 62(2):141–146. doi:10.1016/0304-3959(94)00257-F

    Article  CAS  PubMed  Google Scholar 

  6. Bruera E, Palmer JL, Bosnjak S, Rico MA, Moyano J, Sweeney C, Strasser F, Willey J, Bertolino M, Mathias C, Spruyt O, Fisch MJ (2004) Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. J Clin Oncol 22(1):185–192. doi:10.1200/JCO.2004.03.172

    Article  CAS  PubMed  Google Scholar 

  7. Callegari-Jacques SM (2003) Bioestatística: princípios e aplicações. ARTMED, Porto Alegre

    Google Scholar 

  8. Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, Pandya KJ (1994) Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 330(9):592–596. doi:10.1056/NEJM199403033300902

    Article  CAS  PubMed  Google Scholar 

  9. Curry EA 3rd, Palla S, Hung F, Arbuckle R, Bruera E (2007) Prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital. Am J Health Syst Pharm 64(15):1619–1625. doi:10.2146/ajhp060608

    Article  PubMed  Google Scholar 

  10. Daeninck PJ, Bruera E (1999) Reduction in constipation and laxative requirements following opioid rotation to methadone: a report of four cases. J Pain Symptom Manage 18(4):303–309. doi:10.1016/S0885-3924(99)00086-X

    Article  CAS  PubMed  Google Scholar 

  11. Davis MP, Lasheen W, Gamier P (2007) Practical guide to opioids and their complications in managing cancer pain. What oncologists need to know. Oncology 21(10):1229–1238

    PubMed  Google Scholar 

  12. Drugstore.com. Swedesboro, NJ. http://www.drugstore.com/. Accessed July 4th, 2008

  13. Fisch MJ, Cleeland CS (2003) Managing cancer pain. In: Skeel RT (ed) Handbook of cancer chemotherapy, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 662–663

    Google Scholar 

  14. Foley KM (2001) Supportive care and quality of life. Cancer principles and practice of oncology, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2990–2996

    Google Scholar 

  15. Gomes MS, Cunha GW, Fischmann R, Neuman M (2008) Guia farmacêutico brasíndice no. 662. ANDREI Publicações Médicas, São Paulo

    Google Scholar 

  16. Indelicato RA, Portenoy R (2003) Opioid rotation in the management of refractory cancer pain. J Clin Oncol 21(9):87–91. doi:10.1200/JCO.2003.01.183

    Article  Google Scholar 

  17. Kleinbaum DG, Kupper LL, Muller KE (1998) Applied regression analysis and other multivariable methods. Duxbury, Belmont

    Google Scholar 

  18. Lenth RV (2007) Statistical power calculations. J Anim Sci 85(Suppl 13):E24–E29. doi:10.2527/jas.2006-449

    Article  CAS  PubMed  Google Scholar 

  19. Mercadante S (1999) Opioid rotation for cancer pain: rationale and clinical aspects. Cancer 86(9):1856–1866. doi:10.1002/(SICI)1097-0142(19991101)86:9&lt;1856::AID-CNCR30&gt;3.0.CO;2-G

    Article  CAS  PubMed  Google Scholar 

  20. Mercadante S, Casuccio A, Agnello A, Serretta R, Calderone L, Barresi L (1998) Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. J Clin Oncol 16(11):3656–3661

    CAS  PubMed  Google Scholar 

  21. Mercadante S, Casuccio A, Calderone L (1999) Rapid switching from morphine to methadone in cancer patients with poor response to morphine. J Clin Oncol 17(10):3307–3312

    CAS  PubMed  Google Scholar 

  22. Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P, Gebbia V, Ripamonti C (2001) Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncol 19(11):2898–2904

    CAS  PubMed  Google Scholar 

  23. Mercadante S, Bianchi M, Villari P, Ferrera P, Casuccio A, Fulfaro F, Gebbia V (2003) Opioid plasma concentration during switching from morphine to methadone: preliminary data. Support Care Cancer 11(5):326–331

    CAS  PubMed  Google Scholar 

  24. Mercadante S, Ferrera P, Villari P, Casuccio A (2005) Rapid switching between transdermal fentanyl and methadone in cancer patients. J Clin Oncol 23(22):5229–5234. doi:10.1200/JCO.2005.13.128

    Article  PubMed  Google Scholar 

  25. Mercadante S, Porzio G, Ferrera P, Fulfaro F, Aielli F, Verna L, Villari P, Ficorella C, Gebbia V, Riina S, Casuccio A, Mangione S (2008) Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management. Eur J Pain 12(8):1040–1046. doi:10.1016/j.ejpain.2008.01.013

    Article  CAS  PubMed  Google Scholar 

  26. Morettin P, Bussab W (1982) Estatística básica. Atual ED, São Paulo

    Google Scholar 

  27. Nicholson AB (2007) Methadone for cancer pain. Cochrane Database Syst Rev (4):CD003971

  28. Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F (1998) Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? J Clin Oncol 16(10):3216–3221

    CAS  PubMed  Google Scholar 

  29. Sawe J (1986) High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment. Clin Pharmacokinet 11(2):87–106. doi:10.2165/00003088-198611020-00001

    Article  CAS  PubMed  Google Scholar 

  30. Siegel S (1981) Estatística não paramétrica: para as ciências do comportamento. McGraw-Hill, São Paulo

    Google Scholar 

  31. Stockler M, Vardy J, Pillai A, Warr D (2004) Acetaminophen (paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo-controlled cross-over trial. J Clin Oncol 22(16):3389–3394. doi:10.1200/JCO.2004.09.122

    Article  CAS  PubMed  Google Scholar 

  32. Swegle JM, Wensel DD (2008) The safety of methadone hydrochloride. Expert Opin Drug Saf 7(1):5–8. doi:10.1517/14740338.7.1.5

    Article  CAS  PubMed  Google Scholar 

  33. Vigano A, Fan D, Bruera E (1996) Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators. Pain 67(1):115–119. doi:10.1016/0304-3959(96)03112-0

    Article  CAS  PubMed  Google Scholar 

  34. Watanabe S, Belzile M, Kuehn N, Hanson J, Bruera E (1996) Capsules and suppositories of methadone for patients on high-dose opioids for cancer pain: clinical and economic considerations. Cancer Treat Rev 22:131–136. doi:10.1016/S0305-7372(96)90075-4 Suppl A

    Article  CAS  PubMed  Google Scholar 

  35. WHO (1996) Cancer pain relief: report of a WHO expert committee. World Health Organization, Geneva

    Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Oncology, ABC Foundation School of Medicine, Av. Príncipe de Gales, n. 821, anexo 3, Santo André, São Paulo, ZIP 09060-650, Brazil

    Daniel I. G. Cubero & Auro del Giglio

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  1. Daniel I. G. Cubero
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  2. Auro del Giglio
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Correspondence to Daniel I. G. Cubero.

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Cubero, D.I.G., del Giglio, A. Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study. Support Care Cancer 18, 235–242 (2010). https://doi.org/10.1007/s00520-009-0649-8

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