Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials

Authors: Shailesh M. Advani, Pragati G. Advani, Helena M. VonVille, Syed H. Jafri

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients.

Methods

We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients.

Results

We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients.

Conclusion

Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.
Appendix
Available only for authorised users
Literature
1.
Stephens NA, Skipworth RJ, Fearon KC. Cachexia, survival and the acute phase response. Curr Opin Support Palliat Care. 2008;2:267–74.CrossRef
2.
Zilbermint MF, Dobs AS. Nonsteroidal selective androgen receptor modulator Ostarine™ in cancer cachexia. Future Oncol. 2009;5:1211–20.CrossRef
3.
Mantovani G. Randomised phase III clinical trial of 5 different arms of treatment on 332 patients with cancer cachexia. Eur Rev Med Pharmacol Sci. 2010;14:292–301.PubMed
4.
Dunne RF, Mustian KM, Garcia JM, et al. Research priorities in cancer cachexia: the University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and sarcopenia. Curr Opin Support Palliat Care. 2017;11:278–86.CrossRef
5.
Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489–95.CrossRef
6.
Madeddu C, Mantovani G. An update on promising agents for the treatment of cancer cachexia. Curr Opin Support Palliat Care. 2009;3:258–62.CrossRef
7.
Madeddu C, Maccio A, Panzone F, et al. Medroxyprogesterone acetate in the management of cancer cachexia. Expert Opin Pharmacother. 2009;10:1359–66.CrossRef
8.
Maltoni M, Nanni O, Scarpi E, Rossi D, Serra P, Amadori D. High-dose progestins for the treatment of cancer anorexia-cachexia syndrome: a systematic review of randomised clinical trials. Annals of Oncology. 2001;12(3):289–300.CrossRef
9.
Giordano KF, Jatoi A. The cancer anorexia/weight loss syndrome: therapeutic challenges. Curr Oncol Rep. 2005;7:271–6.CrossRef
10.
Mateen F, Jatoi A. Megestrol acetate for the palliation of anorexia in advanced, incurable cancer patients. Clin Nutr. 2006;25:711–5.CrossRef
11.
Laviano A, Meguid MM, Inui A, et al. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself. Nat Rev Clin Oncol. 2005;2:158.CrossRef
12.
Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior tochemotherapy in cancer patients. Am J Med. 1980;69:491–7.CrossRef
13.
Gullett NP, Hebbar G, Ziegler TR. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting. Am J Clin Nutr. 2010;91:1143S–7S.CrossRef
14.
Morley JE, Thomas DR, Wilson M-MG. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83:735–43.CrossRef
15.
Taylor LA, Pletschen L, Arends J, et al. Marine phospholipids—a promising new dietary approach to tumor-associated weight loss. Support Care Cancer. 2010;18:159.CrossRef
16.
Doyle A, Zhang G, Fattah EAA, et al. Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways. FASEB J. 2011;25:99–110.CrossRef
17.
Zhang G, Jin B, Li YP. C/EBPβ mediates tumour-induced ubiquitin ligase atrogin1/MAFbx upregulation and muscle wasting. EMBO J. 2011;30:4323–35.CrossRef
18.
Zhang G, Liu Z, Ding H, et al. Toll-like receptor 4 mediates Lewis lung carcinoma-induced muscle wasting via coordinate activation of protein degradation pathways. Sci Rep. 2017;7:2273.CrossRef
19.
Yavuzsen T, Davis MP, Walsh D, et al. Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin Oncol. 2005;23:8500–11.CrossRef
20.
VonVille H. Excel workbooks for systematic reviews; 2015.
21.
Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401–6.CrossRef
22.
Strasser F, Luftner D, Possinger K, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-in-Cachexia-study-group. J Clin Oncol. 2006;24:3394–400.CrossRef
23.
24.
Del Fabbro E, Dev R, Hui D, et al. Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial. J Clin Oncol. 2013;31:1271–6.CrossRef
25.
Garcia JM, Boccia RV, Graham CD, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol. 2015;16:108–16.CrossRef
26.
Takayama K, Katakami N, Yokoyama T, et al. Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial. Support Care Cancer. 2016;24:3495–505.CrossRef
27.
Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol. 2016;17:519–31.CrossRef
28.
Currow D, Temel J, Abernethy A, et al. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Ann Oncol. 2017;28:1949–56.CrossRef
29.
Katakami N, Uchino J, Yokoyama T, et al. Anamorelin (ONO-7643) for the treatment of patients with non–small cell lung cancer and cachexia: results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer. 2018;124:606–16.CrossRef
30.
Bai Y, Hu Y, Zhao Y, et al. Anamorelin for cancer anorexia-cachexia syndrome: a systematic review and meta-analysis. Support Care Cancer. 2017;25:1651–9.CrossRef
31.
Nishie K, Yamamoto S, Nagata C, et al. Anamorelin for advanced non-small-cell lung cancer with cachexia: systematic review and meta-analysis. Lung Cancer. 2017;112:25–34.CrossRef
32.
Jatoi A, Dakhil SR, Nguyen PL, et al. A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome. Cancer. 2007;110:1396–403.CrossRef
33.
Jatoi A, Ritter HL, Dueck A, et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9). Lung Cancer. 2010;68:234–9.CrossRef
34.
Gordon J, Trebble T, Ellis R, et al. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut. 2005;54:540–5.CrossRef
35.
Yennurajalingam S, Willey JS, Palmer JL, et al. The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomized study. J Palliat Med. 2012;15:1059–64.CrossRef
36.
Mehrzad V, Afshar R, Akbari M. Pentoxifylline treatment in patients with cancer cachexia: a double-blind, randomized, placebo-controlled clinical trial. Adv Biomed Res. 2016;5:60.CrossRef
37.
Lundholm K, Körner U, Gunnebo L, et al. Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Clin Cancer Res. 2007;13:2699–706.CrossRef
38.
Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14:335–45.CrossRef
39.
Dalton JT, Barnette KG, Bohl CE, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011;2:153–61.CrossRef
40.
Bohl CE, Chang C, Mohler ML, et al. A ligand-based approach to identify quantitative structure− activity relationships for the androgen receptor. J Med Chem. 2004;47:3765–76.CrossRef
41.
Wen H-S, Li X, Cao Y-Z, et al. Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy. 2012;58:461–7.CrossRef
42.
Kanat O, Cubukcu E, Avci N, et al. Comparison of three different treatment modalities in the management of cancer cachexia. Tumori. 2013;99:229–33.CrossRef
43.
Mantovani G, Macciò A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist. 2010;15:200–11.CrossRef
44.
Madeddu C, Dessì M, Panzone F, et al. Randomized phase III clinical trial of a combined treatment with carnitine+ celecoxib±megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr. 2012;31:176–82.CrossRef
45.
Kouchaki B, Janbabai G, Alipour A, et al. Randomized double-blind clinical trial of combined treatment with megestrol acetate plus celecoxib versus megestrol acetate alone in cachexia-anorexia syndrome induced by GI cancers. Support Care Cancer. 2018;26:2479–89.CrossRef
46.
Roeland EJ, Ma JD, Nelson SH, et al. Weight loss versus muscle loss: re-evaluating inclusion criteria for future cancer cachexia interventional trials. Support Care Cancer. 2017;25:365–9.CrossRef
47.
Guillory B, Splenser A, Garcia J. The role of ghrelin in anorexia–cachexia syndromes. In: Vitamins & Hormones: Elsevier; 2013;92:61–106. Academic Press.
48.
Graf SA, Garcia JM. Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome: design, development, and potential place in therapy. Drug Des Devel Ther. 2017;11:2325–31.CrossRef
49.
Deans C, Wigmore SJ. Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nutr Metab Care. 2005;8:265–9.CrossRef
50.
Ando K, Takahashi F, Motojima S, et al. Possible role for tocilizumab, an anti–interleukin-6 receptor antibody, in treating cancer cachexia. J Clin Oncol. 2012;31:e69–72.CrossRef
51.
Bhasin S, Calof OM, Storer TW, et al. Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Rev Endocrinol. 2006;2:146.CrossRef
52.
Crawford J, Johnston M, Hancock M, et al. Enobosarm, a selective androgen receptor modulator (SARM) increases lean body mass (LBM) in advanced NSCLC patients: updated results of two pivotal, international phase 3 trials. Support Care Cancer. 2014;22:S30.
53.
Metadata
Title
Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials
Authors
Shailesh M. Advani
Pragati G. Advani
Helena M. VonVille
Syed H. Jafri
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5080-4

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

New paste for severe stomatitis in patients undergoing head-and-neck cancer radiotherapy and/or chemotherapy with oral appliance

Research article

Characterization of primary normal and malignant breast cancer cell and their response to chemotherapy and immunostimulatory agents

Research article

CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors

Research article

Prevalence and associated risk factors for Kaposi’s sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study

Research article

Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: a retrospective study

Research article

The lymph node status as a prognostic factor in colon cancer: comparative population study of classifications using the logarithm of the ratio between metastatic and nonmetastatic nodes (LODDS) versus the pN-TNM classification and ganglion ratio systems
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits