Efficacy and Safety of Methadone as a Second-Line Opioid for Cancer Pain in an Outpatient Clinic: A Prospective Open-Label Study
Tóm tắt
Most clinical reports on methadone rotation describe outcomes in hospitalized patients. The few studies that have included outpatients are retrospective. The aim of this study was to assess the efficacy and safety of methadone as a second-line opioid in adult patients with advanced cancer after rotation in routine clinical practice at a palliative care outpatient clinic.
This was a prospective, open-label study of 145 patients whose treatment was rotated from other opioids to methadone. Informed consent was obtained in all cases. The main outcome measure was change in the variable “worst pain” at day 28. Pain and pain interference were assessed with the Brief Pain Inventory, with side effects evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Pain levels were evaluated at study entry and at days 3, 7, 9, 14, 21, and 28.
Rotation to methadone was performed for the following reasons: poor pain control (77.9%), opioid side effects (2.1%), or both (20%). The mean daily oral morphine equivalent dose before rotation was 193.7 mg. The median worst and average pain scores decreased significantly (p < .0001) from baseline to day 28: The median worst pain score decreased from 9 (interquartile range [IQR]: 8–10) to 6 (IQR: 3–8), and the median average pain score decreased from 6 (IQR: 5–7) to 4 (IQR: 2–5). The proportions of patients with moderate to severe worst and average pain decreased by 30.3% and 47.5%, respectively, by day 28. No increase in opioid toxicity was observed during the study.
In outpatients with advanced cancer, rotation to methadone as a second-line opioid was efficacious and safe when using a tiered scheme with close follow-up by experienced health professionals.
Từ khóa
Tài liệu tham khảo
De Stoutz, 1995, Opioid rotation for toxicity reduction in terminal cancer patients, J Pain Symptom Manage, 10, 378, 10.1016/0885-3924(95)90924-C
Ashby, 1999, Opioid substitution to reduce adverse effects in cancer pain management, Med J Aust, 170, 68, 10.5694/j.1326-5377.1999.tb126885.x
Kloke, 2000, Toxicity and/or insufficient analgesia by opioid therapy: Risk factors and the impact of changing the opioid. A retrospective analysis of 273 patients observed at a single center, Support Care Cancer, 8, 479, 10.1007/s005200000153
Müller-Busch, 2005, Opioid switch in palliative care, opioid choice by clinical need and opioid availability, Eur J Pain, 9, 571, 10.1016/j.ejpain.2004.12.003
Mercadante, 2009, Frequency, indications, outcomes, and predictive factors of opioid switching in an acute palliative care unit, J Pain Symptom Manage, 37, 632, 10.1016/j.jpainsymman.2007.12.024
Quigley, 2013, WITHDRAWN: Opioid switching to improve pain relief and drug tolerability, Cochrane Database Syst Rev, 10, CD004847
Dale, 2011, European Palliative Care Research Collaborative pain guidelines: Opioid switching to improve analgesia or reduce side effects. A systematic review, Palliat Med, 25, 494, 10.1177/0269216310384902
Shaheen, 2009, Opioid equianalgesic tables: Are they all equally dangerous?, J Pain Symptom Manage, 38, 409, 10.1016/j.jpainsymman.2009.06.004
Mercadante, 2011, Conversion ratios for opioid switching in the treatment of cancer pain: A systematic review, Palliat Med, 25, 504, 10.1177/0269216311406577
Ahmedzai, 1997, Transdermal fentanyl versus sustained-release oral morphine in cancer pain: Preference, efficacy, and quality of life, J Pain Symptom Manage, 13, 254, 10.1016/S0885-3924(97)00082-1
Reid, 2006, Oxycodone for cancer-related pain: Meta-analysis of randomized controlled trials, Arch Intern Med, 166, 837, 10.1001/archinte.166.8.837
Pigni, 2011, The role of hydromorphone in cancer pain treatment: A systematic review, Palliat Med, 25, 471, 10.1177/0269216310387962
Bruera, 2004, Methadone versus morphine as a first-line strong opioid for cancer pain: A randomized, double-blind study, J Clin Oncol, 22, 185, 10.1200/JCO.2004.03.172
Caraceni, 2012, Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC, Lancet Oncol, 13, e58, 10.1016/S1470-2045(12)70040-2
Säwe, 1986, High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment, Clin Pharmacokinet, 11, 87, 10.2165/00003088-198611020-00001
Ferrari, 2004, Methadone–metabolism, pharmacokinetics and interactions, Pharmacol Res, 50, 551, 10.1016/j.phrs.2004.05.002
Bruera, 2002, Methadone use in cancer patients with pain: A review, J Palliat Med, 5, 127, 10.1089/10966210252785097
Leppert, 2009, The role of methadone in cancer pain treatment–a review, Int J Clin Pract, 63, 1095, 10.1111/j.1742-1241.2008.01990.x
Moryl, 2002, Pitfalls of opioid rotation: Substituting another opioid for methadone in patients with cancer pain, Pain, 96, 325, 10.1016/S0304-3959(01)00465-1
Lawlor, 1998, Dose ratio between morphine and methadone in patients with cancer pain: A retrospective study, Cancer, 82, 1167, 10.1002/(SICI)1097-0142(19980315)82:6<1167::AID-CNCR23>3.0.CO;2-3
Bhimji, 2005, Opioid rotation from methadone: Fraught with difficulties, J Pain Symptom Manage, 29, 334, 10.1016/j.jpainsymman.2005.02.006
Walker, 2008, Switching from methadone to a different opioid: What is the equianalgesic dose ratio?, J Palliat Med, 11, 1103, 10.1089/jpm.2007.0285
Rhondali, 2013, Methadone rotation for cancer patients with refractory pain in a palliative care unit: An observational study, J Palliat Med, 16, 1382, 10.1089/jpm.2013.0222
De Conno, 1996, Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients, J Clin Oncol, 14, 2836, 10.1200/JCO.1996.14.10.2836
Hagen, 1999, Methadone: Outpatient titration and monitoring strategies in cancer patients, J Pain Symptom Manage, 18, 369, 10.1016/S0885-3924(99)00083-4
Parsons, 2010, Methadone initiation and rotation in the outpatient setting for patients with cancer pain, Cancer, 116, 520, 10.1002/cncr.24754
Mercadante, 1999, Methadone response in advanced cancer patients with pain followed at home, J Pain Symptom Manage, 18, 188, 10.1016/S0885-3924(99)00048-2
Mercadante, 2013, Opioid switching in patients with advanced cancer followed at home. A retrospective analysis, J Pain Symptom Manage, 45, 298, 10.1016/j.jpainsymman.2012.02.025
Martínez de la Iglesia, 2001, [Spanish language adaptation and validation of the Pfeifferșs questionnaire (SPMSQ) to detect cognitive deterioration in people over 65 years of age], Med Clin (Barc), 117, 129
Rodríguez-Martos, 1986, Validation of the KFA (CBA) and CAGE questionnaires for the diagnosis of alcoholism], Droga-alcohol., 11, 132
Anderson, 1996, Palliative performance scale (PPS): A new tool, J Palliat Care, 12, 5, 10.1177/082585979601200102
Nekolaichuk, 2005, A validation study of a pain classification system for advanced cancer patients using content experts: The Edmonton Classification System for Cancer Pain, Palliat Med, 19, 466, 10.1191/0269216305pm1055oa
Badia, 2003, [Validation of the Spanish version of the Brief Pain Inventory in patients with oncological pain], Med Clin (Barc), 120, 52, 10.1016/S0025-7753(03)73601-X
Serlin, 1995, When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function, Pain, 61, 277, 10.1016/0304-3959(94)00178-H
Porta, 2008, Handbook of symptoms in patients with advanced and terminal cancer, 2nd ed.
ICOPraxi for the medical and radiation treatment of cancer pain [in Spanish], 2nd ed.
Ripamonti, 1998, Switching from morphine to oral methadone in treating cancer pain: What is the equianalgesic dose ratio?, J Clin Oncol, 16, 3216, 10.1200/JCO.1998.16.10.3216
Mercadante, 2001, Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: A prospective study, J Clin Oncol, 19, 2898, 10.1200/JCO.2001.19.11.2898
Mercadante, 1999, Rapid switching from morphine to methadone in cancer patients with poor response to morphine, J Clin Oncol, 17, 3307, 10.1200/JCO.1999.17.10.3307
Mercadante, 2011, The use of fentanyl buccal tablets as breakthrough medication in patients receiving chronic methadone therapy: An open label preliminary study, Support Care Cancer, 19, 435, 10.1007/s00520-010-1015-6
Verebely, 1975, Methadone in man: Pharmacokinetic and excretion studies in acute and chronic treatment, Clin Pharmacol Ther, 18, 180, 10.1002/cpt1975182180
Weschules, 2008, A systematic review of opioid conversion ratios used with methadone for the treatment of pain, Pain Med, 9, 595, 10.1111/j.1526-4637.2008.00461.x
Hernansanz, 2006, Opioid rotation to methadone at home, J Pain Symptom Manage, 31, 2, 10.1016/j.jpainsymman.2005.12.005
Moksnes, 2011, How to switch from morphine or oxycodone to methadone in cancer patients? A randomised clinical phase II trial, Eur J Cancer, 47, 2463, 10.1016/j.ejca.2011.06.047
Chatham, 2013, Dose ratios between high dose oral morphine or equivalents and oral methadone, J Palliat Med, 16, 947, 10.1089/jpm.2012.0434
Cruciani, 2005, Measurement of QTc in patients receiving chronic methadone therapy, J Pain Symptom Manage, 29, 385, 10.1016/j.jpainsymman.2004.06.012
Reddy, 2010, The effect of oral methadone on the QTc interval in advanced cancer patients: A prospective pilot study, J Palliat Med, 13, 33, 10.1089/jpm.2009.0184