Top

BMC Palliative Care

Published in:

Open Access 01-12-2016 | Research article

The association between different opioid doses and the survival of advanced cancer patients receiving palliative care

Authors: Anon Sathornviriyapong, Kittiphon Nagaviroj, Thunyarat Anothaisintawee

Published in: BMC Palliative Care | Issue 1/2016

Abstract

Background

Concerns that opioids may hasten death can be a cause of the physicians’ reluctance to prescribe opioids, leading to inadequate symptom palliation. Our aim was to find if there was an association between different opioid doses and the survival of the cancer patients that participated in our palliative care program.

Methods

A retrospective study was conducted at Ramathibodi Hospital, Bangkok between January 2013 and December 2015. All of the cancer patients that were referred to palliative care teams by their primary physicians were included in the study. The study data included the patients’ demographics, disease status, comorbidities, functional status, type of services, cancer treatments, date of consultation, and the date of the patient’s death or last follow-up. The information concerning opioid use was collected by reviewing the medical records and this was converted to an oral morphine equivalent (OME), following a standard ratio. The time-varying covariate in the Cox regression analysis was applied in order to determine the association between different doses of opioids and patient survival.

Results

A total of 317 cancer patients were included in the study. The median (IQR) of the OME among our patients was 6.43 mg/day (0.53, 27.36). The univariate Cox regression analysis did not show any association between different opioid doses (OME ≤ 30 mg/day and > 30 mg/day) and the patients’ survival (p = 0.52). The PPS levels (p < 0.01), palliative care clinic visits (HR 0.32, 95%CI 0.24–0.43), home visits (HR 0.75, 95%CI 0.57–0.99), chemotherapy (HR 0.32, 95%CI 0.22–0.46), and radiotherapy (HR 0.53, 95%CI 0.36–0.78) were identified as factors that increased the probability of survival.

Conclusions

Our study has demonstrated that different opioid doses in advanced cancer patients are not associated with shortened survival period.

Available only for authorised users

WHO’s cancer pain ladder for adults: World Health Organization. Available from: http://www.who.int/cancer/palliative/painladder/en/. Accessed 1 June 2016.

Lopez-Saca JM, Centeno C. Opioids prescription for symptoms relief and the impact on respiratory function: updated evidence. Curr Opin Support Palliat Care. 2014;8(4):383–90. doi:10.1097/SPC.0000000000000098.CrossRefPubMed

Reis-Pina P, Lawlor PG, Barbosa A. Cancer-related pain management and the optimal use of opioids. Acta Med Port. 2015;28(3):376–81.CrossRefPubMed

Teno JM, Clarridge BR, Casey V, Welch LC, Wetle T, Shield R, et al. Family perspectives on end-of-life care at the last place of care. JAMA. 2004;291(1):88–93.CrossRefPubMed

Garcia-Toyos N, Escudero-Carretero MJ, Sanz-Amores R, Guerra-De Hoyos JA, Melchor-Rodriguez JM, Tamayo-Velazquez MI. Preferences of caregivers and patients regarding opioid analgesic use in terminal care. Pain Med. 2014;15(4):577–87. doi:10.1111/pme.12376.CrossRefPubMed

Janssen DJ, de Hosson SM, bij de Vaate E, Mooren KJ, Baas AA. Attitudes toward opioids for refractory dyspnea in COPD among Dutch chest physicians. Chron Respir Dis. 2015;12(2):85–92. doi:10.1177/1479972315571926.CrossRefPubMed

Lin CC, Wang P, Lai YL, Lin CL, Tsai SL, Chen TT. Identifying attitudinal barriers to family management of cancer pain in palliative care in Taiwan. Palliat Med. 2000;14(6):463–70.CrossRefPubMed

Rocker G, Young J, Donahue M, Farquhar M, Simpson C. Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease. CMAJ. 2012;184(9):E497–504. doi:10.1503/cmaj.111758.CrossRefPubMedPubMedCentral

Rurup ML, Borgsteede SD, van der Heide A, van der Maas PJ, Onwuteaka-Philipsen BD. Trends in the use of opioids at the end of life and the expected effects on hastening death. J Pain Symptom Manage. 2009;37(2):144–55. doi:10.1016/j.jpainsymman.2008.02.010.EpubAug9.CrossRefPubMed

10.

Bercovitch M, Adunsky A. Patterns of high-dose morphine use in a home-care hospice service: should we be afraid of it? Cancer. 2004;101(6):1473–7.CrossRefPubMed

11.

Bengoechea I, Gutierrez SG, Vrotsou K, Onaindia MJ, Lopez JM. Opioid use at the end of life and survival in a Hospital at Home unit. J Palliat Med. 2010;13(9):1079–83. doi:10.89/jpm.2010.0031.CrossRefPubMed

12.

Azoulay D, Hammerman-Rozenberg R, Cialic R, Ein Mor E, Jacobs JM, Stessman J. Increasing opioid therapy and survival in a hospice. J Am Geriatr Soc. 2008;56(2):360–1. doi:10.1111/j.532-5415.2007.01536.x.CrossRefPubMed

13.

Azoulay D, Jacobs JM, Cialic R, Mor EE, Stessman J. Opioids, survival, and advanced cancer in the hospice setting. J Am Med Dir Assoc. 2011;12(2):129–34. doi:10.1016/j.jamda.2010.07.012.EpubOct16.CrossRefPubMed

14.

Good PD, Ravenscroft PJ, Cavenagh J. Effects of opioids and sedatives on survival in an Australian inpatient palliative care population. Intern Med J. 2005;35(9):512–7.CrossRefPubMed

15.

Radha Krishna LK, Poulose JV, Tan BS, Goh C. Opioid use amongst cancer patients at the end of life. Ann Acad Med Singapore. 2010;39(10):790–7.PubMed

16.

Alsirafy SA, Galal KM, Abou-Elela EN, Ibrahim NY, Farag DE, Hammad AM. The use of opioids at the end-of-life and the survival of Egyptian palliative care patients with advanced cancer. Ann Palliat Med. 2013;2(4):173–7. doi:10.3978/j.issn.2224-5820.2013.10.02.PubMed

17.

Minami S, Fujimoto K, Ogata Y, Yamamoto S, Komuta K. Opioids have no negative effect on the survival time of patients with advanced lung cancer in an acute care hospital. Support Care Cancer. 2015;23(8):2245–54. doi:10.1007/s00520-014-2592-6.CrossRefPubMed

18.

Portenoy RK, Sibirceva U, Smout R, Horn S, Connor S, Blum RH, et al. Opioid use and survival at the end of life: a survey of a hospice population. J Pain Symptom Manage. 2006;32(6):532–40.CrossRefPubMed

19.

Lin YL, Lin IC, Liou JC. Symptom patterns of patients with head and neck cancer in a palliative care unit. J Palliat Med. 2011;14(5):556–9. doi:10.1089/jpm.2010.0461.CrossRefPubMed

20.

van Hooft JE, Dijkgraaf MG, Timmer R, Siersema PD, Fockens P. Independent predictors of survival in patients with incurable malignant gastric outlet obstruction: a multicenter prospective observational study. Scand J Gastroenterol. 2010;45(10):1217–22. doi:10.3109/00365521.2010.487916.CrossRefPubMed

21.

Singleton PA, Moss J, Karp DD, Atkins JT, Janku F. The mu opioid receptor: a new target for cancer therapy? Cancer. 2015;121(16):2681–8. doi:10.1002/cncr.29460.CrossRefPubMed

22.

Zylla DM. Impact of opioid use on survival in patients with newly diagnosed stage IV non-hematologic malignancies. 2015 Palliative Care in Oncology Symposium; 2015.

23.

Nguyen J, Luk K, Vang D, Soto W, Vincent L, Robiner S, et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Br J Anaesth. 2014;113 Suppl 1:i4–13. doi:10.1093/bja/aeu090.CrossRefPubMedPubMedCentral

24.

Skipworth RJ, Moses AG, Sangster K, Sturgeon CM, Voss AC, Fallon MT, et al. Interaction of gonadal status with systemic inflammation and opioid use in determining nutritional status and prognosis in advanced pancreatic cancer. Support Care Cancer. 2011;19(3):391–401. doi:10.1007/s00520-010-0832-y.CrossRefPubMed

25.

Halabi S, Lin CY, Kelly WK, Fizazi KS, Moul JW, Kaplan EB, et al. Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2014;32(7):671–7. doi:10.1200/JCO.2013.52.3696.CrossRefPubMedPubMedCentral

26.

Boland JW, Ziegler L, Boland EG, McDermid K, Bennett MI. Is regular systemic opioid analgesia associated with shorter survival in adult patients with cancer? A systematic literature review. Pain. 2015;156(11):2152–63. doi:10.1097/j.pain.0000000000000306.CrossRefPubMed

27.

Lopez-Saca JM, Guzman JL, Centeno C. A systematic review of the influence of opioids on advanced cancer patient survival. Curr Opin Support Palliat Care. 2013;7(4):424–30. doi:10.1097/SPC.0b013e328365763a.CrossRefPubMed

28.

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRefPubMed

29.

Chewaskulyong B, Sapinun L, Downing GM, Intaratat P, Lesperance M, Leautrakul S, et al. Reliability and validity of the Thai translation (Thai PPS Adult Suandok) of the Palliative Performance Scale (PPSv2). Palliat Med. 2012;26(8):1034–41. doi:10.177/0269216311424633.CrossRefPubMed

30.

Mercadante S, Caraceni A. Conversion ratios for opioid switching in the treatment of cancer pain: a systematic review. Palliat Med. 2011;25(5):504–15. doi:10.1177/0269216311406577.CrossRefPubMed

31.

Klepstad P, Kaasa S, Borchgrevink PC. Starting step III opioids for moderate to severe pain in cancer patients: dose titration: a systematic review. Palliat Med. 2011;25(5):424–30. doi:10.1177/0269216310386280.CrossRefPubMed

32.

NICE. Palliative care for adults: strong opioids for pain relief UK2016 [updated August 2016]. Available from: https://www.nice.org.uk/guidance/cg140/resources. Accessed 1 Sept 2016.

33.

Mercadante S, Bruera E. Opioid switching in cancer pain: From the beginning to nowadays. Crit Rev Oncol Hematol. 2016;99:241–8. doi:10.1016/j.critrevonc.2015.12.011.CrossRefPubMed

34.

Naito T, Kawakami J. Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients. Yakugaku Zasshi. 2015;135(5):709–15. doi:10.1248/yakushi.14-00234-4.CrossRefPubMed

35.

Thorns A, Sykes N. Opioid use in last week of life and implications for end-of-life decision-making. Lancet. 2000;356(9227):398–9.CrossRefPubMed

36.

Lennon FE, Mirzapoiazova T, Mambetsariev B, Poroyko VA, Salgia R, Moss J, et al. The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and Epithelial Mesenchymal Transition (EMT) in human lung cancer. PLoS One. 2014;9(3):e91577. doi:10.1371/journal.pone.0091577. eCollection 2014.CrossRefPubMedPubMedCentral

37.

Niu DG, Peng F, Zhang W, Guan Z, Zhao HD, Li JL, et al. Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer. Oncotarget. 2015;6(6):3963–76.CrossRefPubMedPubMedCentral

38.

Sacerdote P, Manfredi B, Mantegazza P, Panerai AE. Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br J Pharmacol. 1997;121(4):834–40.CrossRefPubMedPubMedCentral

39.

Morita T, Tsunoda J, Inoue S, Chihara S. Effects of high dose opioids and sedatives on survival in terminally ill cancer patients. J Pain Symptom Manage. 2001;21(4):282–9.CrossRefPubMed

40.

Sykes N, Thorns A. The use of opioids and sedatives at the end of life. Lancet Oncol. 2003;4(5):312–8.CrossRefPubMed

41.

Kim AS, Youn CH, Ko HJ, Kim HM. The survival time of terminal cancer patients: prediction based on clinical parameters and simple prognostic scores. J Palliat Care. 2014;30(1):24–31.PubMed

42.

Kristensen A, Vagnildhaug OM, Gronberg BH, Kaasa S, Laird B, Solheim TS. Does chemotherapy improve health-related quality of life in advanced pancreatic cancer? A systematic review. Crit Rev Oncol Hematol. 2016;15(16):30008–7.

43.

Mei AH, Jin WL, Hwang MK, Meng YC, Seng LC, Yaw WH. Value of the Palliative Performance Scale in the prognostication of advanced cancer patients in a tertiary care setting. J Palliat Med. 2013;16(8):887–93. doi:10.1089/jpm.2012.0556.CrossRefPubMed

44.

Myers J, Kim A, Flanagan J, Selby D. Palliative performance scale and survival among outpatients with advanced cancer. Support Care Cancer. 2015;23(4):913–8. doi:10.1007/s00520-014-2440-8.CrossRefPubMed

45.

Lloyd-Williams M, Payne S, Reeve J, Dona RK. Thoughts of self-harm and depression as prognostic factors in palliative care patients. J Affect Disord. 2014;166:324–9. doi:10.1016/j.jad.2014.05.029.CrossRefPubMed

46.

Conversion Between Opioid Analgesics: A practical guide from the University of Alberta Multidisciplinary Pain Centre Faculty of Medicine & Dentistry, University of Alberta. Available from: https://www.ualberta.ca/medicine/institutes-centres-groups/multidisciplinary-pain-centre/for-healthcareprofessionals/opioid-conversion-guide. Accessed 1 June 2016.

47.

Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain: Michael G. DeGroote National Pain Centre 2010. Available from: http://nationalpaincentre.mcmaster.ca/opioid/index.html. Accessed 1 June 2016.

48.

Choosing and Changing Opioids: Scottish Palliative Care Guidelines; 2014. Available from: http://www.palliativecareguidelines.scot.nhs.uk/guidelines/pain/choosing-and-changing-opioids.aspx. Accessed 1 June 2016.

49.

Breitbart W, Chandler S, Eagel B, Ellison N, Enck RE, Lefkowitz M, et al. An alternative algorithm for dosing transdermal fentanyl for cancer-related pain. Oncology (Williston Park). 2000;14(5):695–705. discussion.

50.

National List of Essential Medicines: Food and Drug Administration Thailand, Ministry of Public Health. Available from: http://drug.fda.moph.go.th:81/nlem.in.th/medicine/essential/list/73.

Title: The association between different opioid doses and the survival of advanced cancer patients receiving palliative care
Authors: Anon Sathornviriyapong
Kittiphon Nagaviroj
Thunyarat Anothaisintawee
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Palliative Care / Issue 1/2016
Electronic ISSN: 1472-684X
DOI: https://doi.org/10.1186/s12904-016-0169-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The association between different opioid doses and the survival of advanced cancer patients receiving palliative care

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Factors influencing the health-related quality of life of Chinese advanced cancer patients and their spousal caregivers: a cross-sectional study

Improving end of life care in care homes; an evaluation of the six steps to success programme

Barriers to and facilitators for implementing quality improvements in palliative care – results from a qualitative interview study in Norway

Protocol: Evaluating the impact of a nation-wide train-the-trainer educational initiative to enhance the quality of palliative care for children with cancer

HOLD study (Home care Obstructive Lung Disease): natural history of patients with advanced COPD

A palliative care link nurse programme in Mulago Hospital, Uganda: an evaluation using mixed methods