Hostname: page-component-76fb5796d-vfjqv Total loading time: 0 Render date: 2024-04-25T12:45:05.540Z Has data issue: false hasContentIssue false
  • English
  • Français

Prophylaxis and treatment of cancer-related dyspnea with pharmacologic agents: A systematic review and network meta-analysis

Published online by Cambridge University Press:  14 October 2021

Ronald Chow Open the ORCID record for Ronald Chow [Opens in a new window] ,
David Hui ,
Saverio Caini ,
Charles B. Simone II ,
Elizabeth Prsic ,
Gabriel Boldt  and
Michael Lock
Ronald Chow*
Affiliation:
New York Proton Center, Memorial Sloan Kettering Cancer Center, New York, NY London Regional Cancer Program, London Health Sciences Centre, Schulich School of Medicine & Dentistry, London, ON, Canada
David Hui
Affiliation:
MD Anderson Cancer Center University of Texas, Houston, TX
Saverio Caini
Affiliation:
Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy
Charles B. Simone II
Affiliation:
New York Proton Center, Memorial Sloan Kettering Cancer Center, New York, NY
Elizabeth Prsic
Affiliation:
Yale New Haven Hospital, Yale University, New Haven, CT
Gabriel Boldt
Affiliation:
London Regional Cancer Program, London Health Sciences Centre, Schulich School of Medicine & Dentistry, London, ON, Canada
Michael Lock
Affiliation:
London Regional Cancer Program, London Health Sciences Centre, Schulich School of Medicine & Dentistry, London, ON, Canada
*
Author for correspondence: Ronald Chow, New York Proton Center, Memorial Sloan Kettering Cancer Center, New York, NY. E-mail: rchow@nyproton.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction

Cancer-related dyspnea is a common symptom in patients with cancer. It has also been reported to be a predictor of poorer prognosis, which can then change clinical treatment and advance care planning. Currently, no definitive recommendation for pharmacologic agents for cancer-related dyspnea exists. The aim of this systematic review and network meta-analysis is to compare pharmacologic agents for the prophylaxis and treatment of cancer-related dyspnea.

Methods

A search was conducted in the databases of PubMed, Embase, and Cochrane CENTRAL through May 2021. Standardized mean differences (SMDs), as reported by studies or calculated from baseline and follow-up dyspnea scores, were amalgamated into a summary SMD and 95% confidence interval (CI) using a restricted maximum likelihood multivariate network meta-analysis.

Results

Twelve studies were included in this review; six reported on prophylaxis of exertional dyspnea, five on treatment of everyday dyspnea, and one on treatment of episodic dyspnea. Morphine sulfate was better at controlling everyday dyspnea than placebo (SMD 1.210; 95% CI: 0.415–2.005). Heterogeneity in study design and comparisons, however, led to some concerns with the underlying consistency assumption in network meta-analysis design.

Conclusion

Optimal pharmacologic interventions for cancer-related dyspnea could not be determined based on this analysis. Further trials are needed to report on the efficacy of pharmacologic interventions for the prophylaxis and treatment of cancer-related dyspnea.

Keywords

Cancer-related dyspneaMeta-analysisPalliative carePharmacologic interventionsSystematic review
Type
Review Article
Information
Palliative & Supportive Care , Volume 20 , Issue 5 , October 2022 , pp. 744 - 751
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aabom, B, Laier, G, Christensen, PL, et al. (2020) Oral morphine drops for prompt relief of breathlessness in patients with advanced cancer - A randomized, double blinded, crossover trial of morphine sulfate oral drops vs. morphine hydrochloride drops with ethanol (red morphine drops). Supportive Care in Cancer 28(7), 3421–3428. doi:10.1007/s00520-019-05116-1CrossRefGoogle Scholar
Allard, P, Lamontagne, C, Bernard, P, et al. (1999) How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. Journal of Pain and Symptom Management 17(4), 256–265. doi:10.1016/s0885-3924(98)00157-2CrossRefGoogle ScholarPubMed
Bruera, E, MacEachern, T, Ripamonti, C, et al. (1993) Subcutaneous morphine for dyspnea in cancer patients. Annals of Internal Medicine 119(9), 906–907. doi:10.7326/0003-4819-119-9-199311010-00007CrossRefGoogle ScholarPubMed
Bruera, E, Sala, R, Spruyt, O, et al. (2005) Nebulized versus subcutaneous morphine for patients with cancer dyspnea: A preliminary study. Journal of Pain and Symptom Management 29(6), 613–618. doi:10.1016/j.jpainsymman.2004.08.016CrossRefGoogle ScholarPubMed
Charles, MA, Reymond, L and Israel, F (2008) Relief of incident dyspnea in palliative cancer patients: A pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline. Journal of Pain and Symptom Management 36(1), 29–38. doi:10.1016/j.jpainsymman.2007.08.016CrossRefGoogle ScholarPubMed
Feliciano, JL, Waldfogel, JM, Sharma, R, et al. (2021) Pharmacologic interventions for breathlessness in patients with advanced cancer: A systematic review and meta-analysis. JAMA Network Open 4(2), e2037632. doi:10.1001/jamanetworkopen.2020.37632CrossRefGoogle ScholarPubMed
Gamborg, H, Riis, J, Christrup, L, et al. (2013) Effect of intraoral and subcutaneous morphine on dyspnea at rest in terminal patients with primary lung cancer or lung metastases. Journal of Opioid Management 9(4), 269–274. doi:10.5055/jom.2013.0168CrossRefGoogle ScholarPubMed
Hui, D, Xu, A, Frisbee-Hume, S, et al. (2014) Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: A preliminary double-blind, randomized, controlled trial. Journal of Pain and Symptom Management 47(2), 209–217. doi:10.1016/j.jpainsymman.2013.03.017CrossRefGoogle ScholarPubMed
Hui, D, Kilgore, K, Frisbee-Hume, S, et al. (2016a) Dexamethasone for dyspnea in cancer patients: A pilot double-blind, randomized, controlled trial. Journal of Pain and Symptom Management 52(1), 8–16.e11. doi:10.1016/j.jpainsymman.2015.10.023CrossRefGoogle Scholar
Hui, D, Kilgore, K, Park, M, et al. (2016b) Impact of prophylactic fentanyl pectin nasal spray on exercise-induced episodic dyspnea in cancer patients: A double-blind, randomized controlled trial. Journal of Pain and Symptom Management 52(4), 459–468.e451. doi:10.1016/j.jpainsymman.2016.05.013CrossRefGoogle Scholar
Hui, D, Kilgore, K, Frisbee-Hume, S, et al. (2017) Effect of prophylactic fentanyl buccal tablet on episodic exertional dyspnea: A pilot double-blind randomized controlled trial. Journal of Pain and Symptom Management 54(6), 798–805. doi:10.1016/j.jpainsymman.2017.08.001CrossRefGoogle ScholarPubMed
Hui, D, Hernandez, F, Larsson, L, et al. (2019) Prophylactic fentanyl sublingual spray for episodic exertional dyspnea in cancer patients: A pilot double-blind randomized controlled trial. Journal of Pain and Symptom Management 58(4), 605–613. doi:10.1016/j.jpainsymman.2019.06.024CrossRefGoogle ScholarPubMed
Hui, D, Bohlke, K, Bao, T, et al. (2021) Management of dyspnea in advanced cancer: ASCO guideline. Journal of Clinical Oncology 39(12), 1389–1411. doi:10.1200/jco.20.03465CrossRefGoogle ScholarPubMed
Jones, JA and Simone, CB 2nd (2014) Palliative radiotherapy for advanced malignancies in a changing oncologic landscape: Guiding principles and practice implementation. Annals of Palliative Medicine 3(3), 192–202. doi:10.3978/j.issn.2224-5820.2014.07.06Google Scholar
Mazzocato, C, Buclin, T and Rapin, CH (1999) The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: A randomized double-blind controlled trial. Annals of Oncology 10(12), 1511–1514. doi:10.1023/a:1008337624200CrossRefGoogle ScholarPubMed
McGuinness, LA and Higgins, JPT (2020) Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Research Synthesis Methods. doi:10.1002/jrsm.1411Google Scholar
Navigante, AH, Cerchietti, LC, Castro, MA, et al. (2006) Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. Journal of Pain and Symptom Management 31(1), 38–47. doi:10.1016/j.jpainsymman.2005.06.009CrossRefGoogle ScholarPubMed
Navigante, AH, Castro, MA and Cerchietti, LC (2010) Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated. Journal of Pain and Symptom Management 39(5), 820–830. doi:10.1016/j.jpainsymman.2009.10.003CrossRefGoogle ScholarPubMed
Peoples, AR, Bushunow, PW, Garland, SN, et al. (2016) Buspirone for management of dyspnea in cancer patients receiving chemotherapy: A randomized placebo-controlled URCC CCOP study. Supportive Care in Cancer 24(3), 1339–1347. doi:10.1007/s00520-015-2903-6CrossRefGoogle ScholarPubMed
Pinna, M, Vargas, R, Moralo, M, et al. (2009) Dyspnea – A bad prognosis symptom at the end of life. American Journal of Hospice and Palliative Medicine 26(2), 89–97.CrossRefGoogle Scholar
Pinna, M, Bruera, E, Moralo, MJ, et al. (2015) A randomized crossover clinical trial to evaluate the efficacy of oral transmucosal fentanyl citrate in the treatment of dyspnea on exertion in patients with advanced cancer. American Journal of Hospice and Palliative Medicine 32(3), 298–304. doi:10.1177/1049909113513063CrossRefGoogle ScholarPubMed
Simon, ST, Kloke, M, Alt-Epping, B, et al. (2016) EffenDys-fentanyl buccal tablet for the relief of episodic breathlessness in patients with advanced cancer: A multicenter, open-label, randomized, morphine-controlled, crossover, phase II trial. Journal of Pain and Symptom Management 52(5), 617–625. doi:10.1016/j.jpainsymman.2016.05.023CrossRefGoogle ScholarPubMed
Simone, CB 2nd and Jones, JA (2013) Palliative care for patients with locally advanced and metastatic non-small cell lung cancer. Annals of Palliative Medicine 2(4), 178–188. doi:10.3978/j.issn.2224-5820.2013.08.02Google ScholarPubMed
Solano, JP, Gomes, B and Higginson, IJ (2006) A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. Journal of Pain and Symptom Management 31(1), 58–69.CrossRefGoogle ScholarPubMed
Sterne, JAC, Savović, J, Page, MJ, et al. (2019) Rob 2: A revised tool for assessing risk of bias in randomised trials. BMJ 366, l4898. doi:10.1136/bmj.l4898CrossRefGoogle ScholarPubMed
Stone, P, Rix, , Kurowska, A, et al. (2002) Re: Nebulized furosemide for dyspnea in terminal cancer patients. Journal of Pain and Symptom Management 24(3), 274–275. author reply 275-276. doi:10.1016/s0885-3924(02)00479-7CrossRefGoogle ScholarPubMed
Tishelman, C, Petersson, LM, Degner, LF, et al. (2007) Symptom prevalence, intensity, and distress in patients with inoperable lung cancer in relation to time of death. Journal of Clinical Oncology 25(34), 5381–5389.CrossRefGoogle ScholarPubMed
White, IR, Barrett, JK, Jackson, D, et al. (2012) Consistency and inconsistency in network meta-analysis: Model estimation using multivariate meta-regression. Research Synthesis Methods 3(2), 111–125. doi:10.1002/jrsm.1045CrossRefGoogle ScholarPubMed
Wilcock, A, Walton, A, Manderson, C, et al. (2008) Randomised, placebo controlled trial of nebulised furosemide for breathlessness in patients with cancer. Thorax 63(10), 872–875. doi:10.1136/thx.2007.091538CrossRefGoogle ScholarPubMed
Yamaguchi, T, Matsuda, Y, Matsuoka, H, et al. (2018) Efficacy of immediate-release oxycodone for dyspnoea in cancer patient: Cancer dyspnoea relief (CDR) trial. Japanese Journal of Clinical Oncology 48(12), 1070–1075. doi:10.1093/jjco/hyy139CrossRefGoogle ScholarPubMed