Effectiveness of opioid rotation in the control of cancer pain: The ROTODOL Study

Jesús González-Barboteo, MD; Xavier Gómez-Batiste Alentorn, MD, PhD; Felipe A. Calvo Manuel, MD, PhD; Vicente Alberola Candel, MD; M. Amalia Palacios Eito, MD; Isabel Sánchez-Magro, MD, PhD; F. Javier Pérez Martín, PhD; Josep Porta-Sales, MD, PhD

doi:10.5055/jom.2014.0236

Authors

Jesús González-Barboteo, MD
Xavier Gómez-Batiste Alentorn, MD, PhD
Felipe A. Calvo Manuel, MD, PhD
Vicente Alberola Candel, MD
M. Amalia Palacios Eito, MD
Isabel Sánchez-Magro, MD, PhD
F. Javier Pérez Martín, PhD
Josep Porta-Sales, MD, PhD

DOI:

https://doi.org/10.5055/jom.2014.0236

Keywords:

analgesics, opioid/administration and dosage, pain, neoplasms

Abstract

Objective: To assess the effectiveness of opioid rotation (OR) to manage cancer pain. To describe the adverse events (AEs) associated with OR.

Setting: Thirty-nine tertiary hospital services.

Patients: Sixty-seven oncological patients with cancer-related pain treated at outpatient clinics.

Intervention: Prospective multicenter study. Pain intensity was scored using a Numerical Rating Scale (NRS) of 0-10. Average pain (AP) intensity in the last 24 hours, breakthrough pain (BTP), and the number of episodes of BTP on the days before and 1 week after OR were assessed. The pre-OR and post-OR opioid were recorded. The presence and intensity of any AEs occurring after OR were also recorded.

Results: In the 67 patients evaluated, 75 ORs were recorded. In all cases, the main reason for OR was poor pain control. Pain intensity decreased by ≥2 points after OR in 75.4 percent and 57.8 percent of cases for AP and BTP, respectively. If the initial NRS score was ≥4, a decrease below <4 accounted for 50.9 percent and 32.3 percent of cases for AP and BTP, respectively. The number of episodes of BTP also decreased significantly (p < 0.001). A total of 107 AEs were reported, most of which were mild in intensity, with gastrointestinal symptoms predominating.

Conclusions: Opioid rotation appears to be both safe and effective in the management of basal and breakthrough cancer pain.

Author Biographies

Jesús González-Barboteo, MD

Palliative Care Service, Hospital Duran I Reynals, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain; Chair of Palliative Care, Center for Health and Social Studies, University of Vic., Barcelona, Spain; Palliative Care Research Group, IDIBELL, Universitary Bellvitge Hospital, L’Hospitalet de Llobregat, Barcelona, Spain.

Xavier Gómez-Batiste Alentorn, MD, PhD

Director of World Health Organization Collaborating Centre for Public Health Palliative Care Programmes, Hospital Duran I Reynals, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain; Director of Chair of Palliative Care, Center for Health and Social Studies, University of Vic., Barcelona, Spain; Palliative Care Research Group, IDIBELL, Universitary Bellvitge Hospital, L’Hospitalet de Llobregat, Barcelona, Spain.

Felipe A. Calvo Manuel, MD, PhD

Chief of Oncology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Professor of Complutense, University of Madrid, Madrid, Spain.

Vicente Alberola Candel, MD

Chief of Medical Oncology Service, Hospital Arnau de Vilanova, Valencia, Spain; Professor of Medical Oncology, Medical Oncology Service, Hospital Arnau de Vilanova, Universitat de Valencia, Valencia, Spain.

M. Amalia Palacios Eito, MD

Chief of Radiotherapy Oncology Service, Hospital Universitario Provincial Reina Sofía, Córdoba, Spain.

Isabel Sánchez-Magro, MD, PhD

Medical Director of Medical Department, Grünenthal Iberia, Madrid, Spain. Marta Neira Álvarez, MD, PhD, Medical Department, Grünenthal Iberia, Madrid, Spain.

F. Javier Pérez Martín, PhD

Clinical Research Unit, Hospital Duran I Reynals, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain

Josep Porta-Sales, MD, PhD

Chief of Palliative Care Service Research Unit, Hospital Duran I Reynals, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain; Palliative Care Research Group, IDIBELL, Universitary Bellvitge Hospital, L’Hospitalet de Llobregat, Barcelona, Spain.

References

World Health Organization: WHO Cancer Pain Relief, with a Guide to Opioid Availability. Geneva: World Health Organization, 1996.

Zech DF, Grond S, Lynch J, et al.: Validation of World Health Organization Guidelines for cancer pain relief: A 10-year prospective study. Pain. 1995; 63(1): 65-76. DOI: https://doi.org/10.1016/0304-3959(95)00017-M

Porta-Sales J, Gómez-Batiste X, Tuca-Rodriguez A, et al.: WHO analgesic ladder—Or lift? Eur J Palliat Care. 2003; 10: 105-109.

Hanks GW, Conno F, Cherny N, et al.: Morphine and alternative opioids in cancer pain: The EAPC recommendations. Br J Cancer. 2001; 84(5): 587-593. DOI: https://doi.org/10.1054/bjoc.2001.1680

Mercadante S, Portenoy RK: Opioid poorly-responsive cancer pain. Part 1: Clinical considerations. J Pain Symptom Manage. 2001; 21(2): 144-150. DOI: https://doi.org/10.1016/S0885-3924(00)00228-1

González-Barboteo J, Trelis-Navarro J, Tuca-Rodríguez A, et al.: Opioid rotation: A therapeutic choice in the management of refractory cancer pain. Med Clin (Barc). 2010; 135(13): 617-622. DOI: https://doi.org/10.1016/j.medcli.2010.06.006

Quigley C: Opioid switching to improve pain relief and drug tolerability. Cochrane Database Syst Rev. 2004; 3(3): CD004847. DOI: https://doi.org/10.1002/14651858.CD004847

Mercadante S, Bruera E: Opioid switching: A systematic and critical review. Cancer Treat Rev. 2006; 32(4): 304-315. DOI: https://doi.org/10.1016/j.ctrv.2006.03.001

Vadalouca A, Moka E, Argyra E, et al.: Opioid rotation in patients with cancer: A review of the current literature. J Opioid Manag. 2008; 4(4): 213-250. DOI: https://doi.org/10.5055/jom.2008.0027

Mercadante S: Opioid rotation for cancer pain: Rationale and clinical aspects. Cancer. 1999; 86(9): 1856-1866. DOI: https://doi.org/10.1002/(SICI)1097-0142(19991101)86:9<1856::AID-CNCR30>3.0.CO;2-G

Ross JR, Riley J, Quigley C, et al.: Clinical pharmacology and pharmacotherapy of opioid switching in cancer patients. Oncologist. 2006; 11(7): 765-773. DOI: https://doi.org/10.1634/theoncologist.11-7-765

Pasternak GW: Incomplete cross tolerance and multiple mu opioid peptide receptors. Trends Pharmacol Sci. 2001; 22(2): 67-70. DOI: https://doi.org/10.1016/S0165-6147(00)01616-3

Bolan EA, Tallarida RJ, Pasternak GW: Synergy between mu opioid ligands: Evidence for functional interactions among mu opioid receptor subtypes. J Pharmacol Exp Ther. 2002; 303(2): 557-562. DOI: https://doi.org/10.1124/jpet.102.035881

Dong Z, Cao J, Xu L: Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo. Neuroscience. 2007; 144(3): 845-854. DOI: https://doi.org/10.1016/j.neuroscience.2006.10.018

Pu L, Bao G-B, Xu N-J, et al.: Hippocampal long-term potentiation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates. J Neurosci. 2002; 22(5): 1914-1921. DOI: https://doi.org/10.1523/JNEUROSCI.22-05-01914.2002

Ho S-T, Wang J-J, Huang J-C, et al.: The magnitude of acute tolerance to morphine analgesia: Concentration-dependent or time-dependent? Anesth Analg. 2002; 95(4): 948-951. DOI: https://doi.org/10.1213/00000539-200210000-00029

Fischer BD, Carrigan KA, Dykstra LA: Effects of N-methyld-aspartate receptor antagonists on acute morphine-induced and l-methadone-induced antinociception in mice. J Pain. 2005; 6(7): 425-433. DOI: https://doi.org/10.1016/j.jpain.2005.02.003

Baker AK, Hoffmann VLH, Meert TF: Dextromethorphan and ketamine potentiate the antinociceptive effects of mu- but not delta- or kappa-opioid agonists in a mouse model of acute pain. Pharmacol Biochem Behav. 2002; 74(1): 73-86. DOI: https://doi.org/10.1016/S0091-3057(02)00961-9

Duttaroy A, Yoburn BC: The effect of intrinsic efficacy on opioid tolerance. Anesthesiology. 1995; 82(5): 1226-1236. DOI: https://doi.org/10.1097/00000542-199505000-00018

Riley J, Ross JR, Rutter D, et al.: No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer. 2006; 14(1): 56-64. DOI: https://doi.org/10.1007/s00520-005-0843-2

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

Cherny NJ, Chang V, Frager G, et al.: Opioid pharmacotherapy in the management of cancer pain: A survey of strategies used by pain physicians for the selection of analgesic drugs and routes of administration. Cancer. 1995; 76(7): 1283-1293. DOI: https://doi.org/10.1002/1097-0142(19951001)76:7<1283::AID-CNCR2820760728>3.0.CO;2-0

De Stoutz ND, Bruera E, Suarez-Almazor M: Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage. 1995; 10(5): 378-384. DOI: https://doi.org/10.1016/0885-3924(95)90924-C

Ashby MA, Martin P, Jackson KA: Opioid substitution to reduce adverse effects in cancer pain management. Med J Aust. 1999; 170(2): 68-71. DOI: https://doi.org/10.5694/j.1326-5377.1999.tb126885.x

Bruera E, Pereira J, Watanabe S, et al.: Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer. 1996; 78(4): 852-857. DOI: https://doi.org/10.1002/(SICI)1097-0142(19960815)78:4<852::AID-CNCR23>3.0.CO;2-T

Gagnon B, Bruera E: Differences in the ratios of morphine to methadone in patients with neuropathic pain versus non-neuropathic pain. J Pain Symptom Manage. 1999; 18(2): 120-125. DOI: https://doi.org/10.1016/S0885-3924(99)00049-4

Mercadante S, Ferrera P, Villari P, et al.: Frequency, indications, outcomes, and predictive factors of opioid switching in an acute palliative care unit. J Pain Symptom Manage. 2009; 37(4): 632-641. DOI: https://doi.org/10.1016/j.jpainsymman.2007.12.024

Bruera E, MacMillan K, Hanson J, et al.: The Edmonton Staging System for cancer pain: Preliminary report. Pain. 1989; 37(2): 203-209. DOI: https://doi.org/10.1016/0304-3959(89)90131-0

Porta-Sales J, Rodriguez-Mesa D, Sala-Rovira C: Dolor. In Porta-Sales J, Gómez-Batiste X, Tuca-Rodríguez A (eds.): Manual de control de síntomas en pacientes con cáncer avanzado y terminal. 2nd ed. Madrid: Arán Ediciones S.L., 2008: 45-111.

U.S. Department of Health and Human Services. National Institutes of Health National: Common Terminology Criteria for Adverse Events (CTCAE) version v4.03. 2010. Available at http://www.hrc.govt.nz/sites/default/files/CTCAE%20manual%20-%20DMCC.pdf. Accessed November 11, 2014.

Porta-Sales J, Codorniu N, Gómez-Batiste X, et al.: Patient appointment process, symptom control and prediction of follow-up compliance in a palliative care outpatient clinic. J Pain Symptom Manage. 2005; 30(2): 145-153. DOI: https://doi.org/10.1016/j.jpainsymman.2005.03.008

Daut RL, Cleeland CS: The prevalence and severity of pain in cancer. Cancer. 1982; 50(9): 1913-1918. DOI: https://doi.org/10.1002/1097-0142(19821101)50:9<1913::AID-CNCR2820500944>3.0.CO;2-R

Serlin RC, Mendoza TR, Nakamura Y, et al.: When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995; 61(2): 277-284. DOI: https://doi.org/10.1016/0304-3959(94)00178-H

Müller-Busch HC, Lindena G, Tietze K, et al.: Opioid switch in palliative care, opioid choice by clinical need and opioid availability. Eur J Pain. 2005; 9(5): 571-579. DOI: https://doi.org/10.1016/j.ejpain.2004.12.003

Mercadante S, Casuccio A, Tirelli W, et al.: Equipotent doses to switch from high doses of opioids to transdermal buprenorphine. Support Care Cancer. 2009; 17(6): 715-718. DOI: https://doi.org/10.1007/s00520-008-0546-6

Gatti A, Reale C, Luzi M, et al.: Effects of opioid rotation in chronic pain patients: ORTIBARN study. Clin Drug Investig. 2010; 30(Suppl 2): 39-47. DOI: https://doi.org/10.2165/1158413-S0-000000000-00000

Farrar JT: What is clinically meaningful: Outcome measures in pain clinical trials. Clin J Pain. 2000; 16(2 Suppl): S106-S112. DOI: https://doi.org/10.1097/00002508-200006001-00018

Farrar JT, Portenoy RK, Berlin JA, et al.: Defining the clinically important difference in pain outcome measures. Pain. 2000; 88(3): 287-294. DOI: https://doi.org/10.1016/S0304-3959(00)00339-0

Kloke M, Rapp M, Bosse B, et al.: 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. 2000; 8(6): 479-486. DOI: https://doi.org/10.1007/s005200000153

Mercadante S, Portenoy RK: Opioid poorly-responsive cancer pain. Part 2: Basic mechanisms that could shift dose response for analgesia. J Pain Symptom Manage. 2001; 21(3): 255-264. DOI: https://doi.org/10.1016/S0885-3924(00)00236-0

Collin E, Poulain P, Gauvain-Piquard A, et al.: Is disease progression the major factor in morphine “tolerance” in cancer pain treatment? Pain. 1993; 55(3): 319-326. DOI: https://doi.org/10.1016/0304-3959(93)90007-C

Fainsinger RL, Nekolaichuk CL, Lawlor PG, et al.: A multicenter study of the revised Edmonton Staging System for classifying cancer pain in advanced cancer patients. J Pain Symptom Manage. 2005; 29(3): 224-237. DOI: https://doi.org/10.1016/j.jpainsymman.2004.05.008

Mercadante S, Ferrera P, Villari P, et al.: Hyperalgesia: An emerging iatrogenic syndrome. J Pain Symptom Manage. 2003; 26(2): 769-775. DOI: https://doi.org/10.1016/S0885-3924(03)00258-6

Mercadante S, Arcuri E: Hyperalgesia and opioid switching. Am J Hosp Palliat Care. 2005; 22(4): 291-294. DOI: https://doi.org/10.1177/104990910502200411