Emerging Treatment Options For Cancer-Associated Cachexia: A Literature Review

References

• Naito T. Evaluation of the true endpoint of clinical trials for cancer cachexia. Asia Pac J Oncol Nurs. 2019;6(3):227–233. doi:10.4103/apjon.apjon_68_1831259217
   PubMed Web of Science ®Google Scholar
• KATZ AM, KATZ PB. Diseases of the heart in the works of hippocrates. Br Heart J. 1962;24:257–264. doi:10.1136/hrt.24.3.25714454369
   PubMedGoogle Scholar
• Warren S. The immediate cause of death in cancer. Am J Med Sci. 1932;184:610–619. doi:10.1097/00000441-193211000-00002
   Google Scholar
• Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–495. doi:10.1016/S1470-2045(10)70218-721296615
   PubMed Web of Science ®Google Scholar
• Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH. Cancer-associated cachexia. Nat Rev Dis Primers. 2018;4:17105. doi:10.1038/nrdp.2017.10529345251
   PubMed Web of Science ®Google Scholar
• Argiles JM, Busquets S, Stemmler B, et al. Cachexia and sarcopenia: mechanisms and potential targets for intervention. Curr Opin Pharmacol. 2015;22:100–106.25974750
   PubMed Web of Science ®Google Scholar
• Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315(26):1650–1659.3537791
   PubMed Web of Science ®Google Scholar
• Timmerman KL, Flynn MG, Coen PM, et al. Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise?.J Leukoc Biol. 2008;84(5):1271–1278.18664531
   PubMed Web of Science ®Google Scholar
• Koelwyn GJ, Quail DF, Zhang X, et al. Exercise-dependent regulation of the tumour microenvironment. Nat Rev Cancer. 2017;17(10):620–632.28943640
   PubMed Web of Science ®Google Scholar
• Drummond MJ, Dreyer HC, Fry CS, Glynn EL, Rasmussen BB. Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J Appl Physiol (1985). 2009;106(4):1374–1384. doi:10.1152/japplphysiol.91397.200819150856
   PubMed Web of Science ®Google Scholar
• Lundholm K, Edstrom S, Ekman L, Karlberg I, Bylund AC, Scherstén T. A comparative study of the influence of malignant tumor on host metabolism in mice and man: evaluation of an experimental model. Cancer. 1978;42(2):453–461. doi:10.1002/1097-0142(197808)42:2<453::aid-cncr2820420212>3.0.co;2-t679148
   PubMed Web of Science ®Google Scholar
• Garcia JM, Li H, Mann D, et al. Hypogonadism in male patients with cancer. Cancer. 2006;106(12):2583–2591. doi:10.1002/cncr.2188916688773
   PubMed Web of Science ®Google Scholar
• Shimizu Y, Nagaya N, Isobe T, et al. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res. 2003;9(2):774–778.12576449
   PubMed Web of Science ®Google Scholar
• Garcia JM, Garcia-Touza M, Hijazi RA, et al. Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab. 2005;90(5):2920–2926. doi:10.1210/jc.2004-178815713718
   PubMed Web of Science ®Google Scholar
• Crown AL, Cottle K, Lightman SL, et al. What is the role of the insulin-like growth factor system in the pathophysiology of cancer cachexia, and how is it regulated? Clin Endocrinol (Oxf). 2002;56(6):723–733. doi:10.1046/j.1365-2265.2002.01540.x12072041
   PubMed Web of Science ®Google Scholar
• Dev R, Bruera E, Dalal S. Insulin resistance and body composition in cancer patients. Ann Oncol. 2018;29(suppl_2):ii18–ii26. doi:10.1093/annonc/mdx81529506229
   PubMed Web of Science ®Google Scholar
• Burfeind KG, Michaelis KA, Marks DL. The central role of hypothalamic inflammation in the acute illness response and cachexia. Semin Cell Dev Biol. 2016;54:42–52. doi:10.1016/j.semcdb.2015.10.03826541482
   PubMed Web of Science ®Google Scholar
• Naito T, Okayama T, Aoyama T, et al. Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non-small-cell lung cancer. BMC Cancer. 2017;17(1):571. doi:10.1186/s12885-017-3562-428841858
   PubMed Web of Science ®Google Scholar
• Kinsey E, Ajazi E, Wang X, Johnston MAM, Crawford J. Predictors of physical and functional loss in advanced-stage lung cancer patients receiving platinum chemotherapy. J Thorac Oncol. 2018;13(9):1294–1301. doi:10.1016/j.jtho.2018.05.02929981438
   PubMed Web of Science ®Google Scholar
• Correa-de-Araujo R, Harris-Love MO, Miljkovic I, Fragala MS, Anthony BW, Manini TM. The need for standardized assessment of muscle quality in skeletal muscle function deficit and other aging-related muscle dysfunctions: a symposium report. Front Physiol. 2017;8:87. doi:10.3389/fphys.2017.0008728261109
   PubMed Web of Science ®Google Scholar
• Ruas JL, White JP, Rao RR, et al. A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell. 2012;151(6):1319–1331. doi:10.1016/j.cell.2012.10.05023217713
   PubMed Web of Science ®Google Scholar
• Moses AW, Slater C, Preston T, Barber MD, Fearon KCH. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3fatty acids. Br J Cancer. 2004;90(5):996–1002. doi:10.1038/sj.bjc.660162014997196
   PubMed Web of Science ®Google Scholar
• Morikawa A, Naito T, Sugiyama M, et al. Impact of cancer cachexia on hospitalization-associated physical inactivity in elderly patients with advanced non-small-cell lung cancer. Asia Pac J Oncol Nurs. 2018;5(4):377–382. doi:10.4103/apjon.apjon_20_1830271819
   PubMed Web of Science ®Google Scholar
• Arthur ST, Van Doren BA, Roy D, Noone JM, Zacherle E, Blanchette CM. Cachexia among US cancer patients. J Med Econ. 2016;19(9):874–880. doi:10.1080/13696998.2016.118164027100202
   PubMed Web of Science ®Google Scholar
• Naito T, Okayama T, Aoyama T, et al. Unfavorable impact of cancer cachexia on activity of daily living and need for inpatient care in elderly patients with advanced non-small-cell lung cancer in Japan: a prospective longitudinal observational study. BMC Cancer. 2017;17(1):800. doi:10.1186/s12885-017-3795-229183277
   PubMed Web of Science ®Google Scholar
• Chowdhry SM, Chowdhry VK. Cancer cachexia and treatment toxicity. Curr Opin Support Palliat Care. 2019 [Epub ahead of print]. doi:10.1097/SPC.0000000000000450
   PubMed Web of Science ®Google Scholar
• Fujio T, Nakashima K, Naito T, et al. Platinum combination chemotherapy is poorly tolerated in malnourished advanced lung cancer patients with poor performance status. Nutr Cancer. 2019;71(5):767–771. doi:10.1080/01635581.2018.155994130686047
   PubMed Web of Science ®Google Scholar
• Ross PJ, Ashley S, Norton A, et al. Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer. 2004;90(10):1905–1911. doi:10.1038/sj.bjc.660178115138470
   PubMed Web of Science ®Google Scholar
• Andreyev HJ, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34(4):503–509. doi:10.1016/s0959-8049(97)10090-99713300
   PubMed Web of Science ®Google Scholar
• Takayama K, Atagi S, Imamura F, et al. Quality of life and survival survey of cancer cachexia in advanced non-small cell lung cancer patients-Japan nutrition and QOL survey in patients with advanced non-small cell lung cancer study. Support Care Cancer. 2016;24(8):3473–3480. doi:10.1007/s00520-016-3156-827003901
   PubMed Web of Science ®Google Scholar
• Kimura M, Naito T, Kenmotsu H, et al. Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer. Support Care Cancer. 2015;23(6):1699–1708. doi:10.1007/s00520-014-2534-325430482
   PubMed Web of Science ®Google Scholar
• Kubo Y, Naito T, Mori K, Osawa G, Aruga E. Skeletal muscle loss and prognosis of breast cancer patients. Support Care Cancer. 2017;25(7):2221–2227. doi:10.1007/s00520-017-3628-528204990
   PubMed Web of Science ®Google Scholar
• Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol. 2013;31(25):3076–3082. doi:10.1200/JCO.2012.44.466123897970
   PubMed Web of Science ®Google Scholar
• Ruiz-Garcia V, Lopez-Briz E, Carbonell-Sanchis R, Bort-Martí S, Gonzálvez-Perales JL. Megestrol acetate for cachexia-anorexia syndrome. A systematic review. J Cachexia Sarcopenia Muscle. 2018;9(3):444–452. doi:10.1002/jcsm.1229229542279
   PubMed Web of Science ®Google Scholar
• Solheim TS, Fearon KC, Blum D, Kaasa S. Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncol. 2013;52(1):6–17. doi:10.3109/0284186X.2012.72453623020528
   PubMed Web of Science ®Google Scholar
• Reid J, Mills M, Cantwell M, et al. Thalidomide for managing cancer cachexia. Cochrane Database Syst Rev. 2012;(4):CD008664.
   PubMedGoogle Scholar
• Lavriv DS, Neves PM, Ravasco P. Should omega-3 fatty acids be used for adjuvant treatment of cancer cachexia? Clin Nutr ESPEN. 2018;25:18–25. doi:10.1016/j.clnesp.2018.02.00629779814
   PubMed Web of Science ®Google Scholar
• Aapro M, Arends J, Bozzetti F, et al. Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force. Ann Oncol. 2014;25(8):1492–1499. doi:10.1093/annonc/mdu08524569913
   PubMed Web of Science ®Google Scholar
• Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. 2017;36(1):11–48. doi:10.1016/j.clnu.2016.07.01527637832
   PubMed Web of Science ®Google Scholar
• Stewart Coats AJ, Ho GF, Prabhash K, et al. Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer: a randomized, double-blind, placebo-controlled, international multicentre phase II study (the ACT-ONE trial). J Cachexia Sarcopenia Muscle. 2016;7(3):355–365. doi:10.1002/jcsm.1212627386169
   PubMed Web of Science ®Google Scholar
• Wright TJ, Dillon EL, Durham WJ, et al. A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women. J Cachexia Sarcopenia Muscle. 2018;9(3):482–496. doi:10.1002/jcsm.1229529654645
   PubMed Web of Science ®Google Scholar
• Turcott JG, Del Rocío Guillen Núñez M, Flores-Estrada D, et al. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Support Care Cancer. 2018;26(9):3029–3038. doi:10.1007/s00520-018-4154-929550881
   PubMed Web of Science ®Google Scholar
• Golan T, Geva R, Richards D, et al. LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial. J Cachexia Sarcopenia Muscle. 2018;9(5):871–879. doi:10.1002/jcsm.1233130051975
   PubMed Web of Science ®Google Scholar
• Garcia JM, Polvino WJ. Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers. Oncologist. 2007;12(5):594–600. doi:10.1634/theoncologist.12-5-59417522248
   PubMed Web of Science ®Google Scholar
• Garcia JM, Friend J, Allen S. Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support Care Cancer. 2013;21(1):129–137. doi:10.1007/s00520-012-1500-122699302
   PubMed Web of Science ®Google Scholar
• 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(1):108–116. doi:10.1016/S1470-2045(14)71154-425524795
   PubMed Web of Science ®Google Scholar
• 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(8):3495–3505. doi:10.1007/s00520-016-3144-z27005463
   PubMed Web of Science ®Google Scholar
• 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(3):606–616. doi:10.1002/cncr.3112829205286
   PubMed Web of Science ®Google Scholar
• 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(4):519–531. doi:10.1016/S1470-2045(15)00558-626906526
   PubMed Web of Science ®Google Scholar
• Currow D, Temel JS, Abernethy A, Milanowski J, Friend J, Fearon KC. 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(8):1949–1956. doi:10.1093/annonc/mdx19228472437
   PubMed Web of Science ®Google Scholar
• Hamauchi S, Furuse J, Takano T, et al. A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in advanced gastrointestinal cancer patients with cancer cachexia. Cancer. 2019 [Epub ahead of print]. doi:10.1002/cncr.32406
   PubMed Web of Science ®Google Scholar
• Nishie K, Yamamoto S, Nagata C, Koizumi T, Hanaoka M. Anamorelin for advanced non-small-cell lung cancer with cachexia: systematic review and meta-analysis. Lung Cancer. 2017;112:25–34. doi:10.1016/j.lungcan.2017.07.02329191597
   PubMed Web of Science ®Google Scholar
• 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(5):1651–1659. doi:10.1007/s00520-016-3560-028074289
   PubMed Web of Science ®Google Scholar
• Hong DS, Hui D, Bruera E, et al. MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol. 2014;15(6):656–666. doi:10.1016/S1470-2045(14)70155-X24746841
   PubMed Web of Science ®Google Scholar
• Hickish T, Andre T, Wyrwicz L, et al. MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2017;18(2):192–201.28094194
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Assessment report. Human IGG1 monoclonal antibody specific for human interleukin-1 alpha XBiotech. EMA/CHMP/552293/2017; 9 14, 2017 Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/human-igg1-monoclonal-antibody-specific-human-interleukin-1-alpha-xbiotech Accessed 825, 2019.
   Google Scholar
• U.S. National Library of Medicine. ClinicalTrials.gov: a Phase III study of Xilonix in PATIENTS With Advanced Colorectal Cancer (XCITE). Available from: https://clinicaltrials.gov/ct2/show/NCT01767857 Accessed 8 25, 2019.
   Google Scholar
• Chen J, Hwang DJ, Chung K, et al. In vitro and in vivo structure-activity relationships of novel androgen receptor ligands with multiple substituents in the B-ring. Endocrinology. 2005;146(12):5444–5454.16166218
   PubMed Web of Science ®Google Scholar
• 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(3):153–161.22031847
   PubMed Web of Science ®Google Scholar
• 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(4):335–345.23499390
   PubMed Web of Science ®Google Scholar
• Crawford J, Prado CM, Johnston MA, et al. Study design and rationale for the Phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER trials). Curr Oncol Rep. 2016;18(6):37.27138015
   PubMed Web of Science ®Google Scholar
• U.S. National Library of Medicine. ClinicalTrials.gov: Phase III study of the effect of GTx-024 on muscle wasting in patients with Non-Small Cell Lung Cancer (NSCLC). Available from: https://clinicaltrials.gov/ct2/show/NCT01355484 Accessed 825,2019.
   Google Scholar
• U.S. National Library of Medicine. ClinicalTrials.gov: effect of GTx-024 on muscle wasting in patients with Non-Small Cell Lung Cancer (NSCLC) on first line platinum. Available from: https://clinicaltrials.gov/ct2/show/NCT01355497 Accessed 8 25, 2019.
   Google Scholar
• Mantovani G, Maccio 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(2):200–211.20156909
   PubMed Web of Science ®Google Scholar
• Wen HS, Li X, Cao YZ, et al. Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy. 2012;58(6):461–467.23406994
   PubMed Web of Science ®Google Scholar
• Maccio A, Madeddu C, Gramignano G, et al. A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol. 2012;124(3):417–425.22198049
   PubMed Web of Science ®Google Scholar
• Jatoi A, Rowland K, Loprinzi CL, et al. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J Clin Oncol. 2004;22(12):2469–2476.15197210
   PubMed Web of Science ®Google Scholar
• Madeddu C, Dessi 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(2):176–182.22047681
   PubMed Web of Science ®Google Scholar
• 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(7):2479–2489.29442239
   PubMed Web of Science ®Google Scholar
• Baldwin C. The effectiveness of nutritional interventions in malnutrition and cachexia. Proc Nutr Soc. 2015;74(4):397–404.26087760
   PubMed Web of Science ®Google Scholar
• Blackwood HA, Hall CC, Balstad TR, et al. A systematic review examining nutrition support interventions in patients with incurable cancer. Support Care Cancer. 2019 [Epub ahead of print]. doi:10.1007/s00520-019-04999-4
   PubMed Web of Science ®Google Scholar
• Oberholzer R, Hopkinson JB, Baumann K, et al. Psychosocial effects of cancer cachexia: a systematic literature search and qualitative analysis. J Pain Symptom Manage. 2013;46(1):77–95.23159682
   PubMed Web of Science ®Google Scholar
• Murphy RA, Yeung E, Mazurak VC, et al. Influence of eicosapentaenoic acid supplementation on lean body mass in cancer cachexia. Br J Cancer. 2011;105(10):1469–1473.21970879
   PubMed Web of Science ®Google Scholar
• de van der Schueren MAE, Laviano A, Blanchard H, et al. Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials. Ann Oncol. 2018;29(5):1141–1153.29788170
   PubMed Web of Science ®Google Scholar
• Scott JM, Zabor EC, Schwitzer E, et al. Efficacy of exercise therapy on cardiorespiratory fitness in patients with cancer: a systematic review and meta-analysis. J Clin Oncol. 2018;36(22):2297–2305.29894274
   PubMed Web of Science ®Google Scholar
• Heywood R, McCarthy AL, Skinner TL. Efficacy of exercise interventions in patients with advanced cancer: a systematic review. Arch Phys Med Rehabil. 2018;99(12):2595–2620.29738745
   PubMed Web of Science ®Google Scholar
• Stene GB, Helbostad JL, Balstad TR, et al. Effect of physical exercise on muscle mass and strength in cancer patients during treatment–a systematic review. Crit Rev Oncol Hematol. 2013;88(3):573–593.23932804
   PubMed Web of Science ®Google Scholar
• Grande AJ, Silva V, Riera R, et al. Exercise for cancer cachexia in adults. Cochrane Database Syst Rev. 2014;(11):CD010804.25424884
   PubMed Web of Science ®Google Scholar
• Maddocks M, Murton AJ, Wilcock A. Therapeutic exercise in cancer cachexia. Crit Rev Oncog. 2012;17(3):285–292.22831159
   PubMedGoogle Scholar
• Dittus KL, Gramling RE, Ades PA. Exercise interventions for individuals with advanced cancer: a systematic review. Prev Med. 2017;104:124–132.28716654
   PubMed Web of Science ®Google Scholar
• Solheim TS, Laird BJA, Balstad TR, et al. A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer. J Cachexia Sarcopenia Muscle. 2017;8(5):778–788.28614627
   PubMed Web of Science ®Google Scholar
• Solheim TS, Laird BJA, Balstad TR, et al. Cancer cachexia: rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial. BMJ Support Palliat Care. 2018;8(3):258–265.
   PubMed Web of Science ®Google Scholar
• Uster A, Ruehlin M, Mey S, et al. Effects of nutrition and physical exercise intervention in palliative cancer patients: a randomized controlled trial. Clin Nutr. 2018;37(4):1202–1209.28651827
   PubMed Web of Science ®Google Scholar
• Hall CC, Cook J, Maddocks M, et al. Combined exercise and nutritional rehabilitation in outpatients with incurable cancer: a systematic review. Support Care Cancer. 2019;27(7):2371–2384.30944994
   PubMed Web of Science ®Google Scholar
• Naito T, Mitsunaga S, Miura S, et al. Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer. J Cachexia Sarcopenia Muscle. 2019;10(1):73–83.30334618
   PubMed Web of Science ®Google Scholar
• Mouri T, Naito T, Morikawa A, et al. Promotion of behavioral change and the impact on quality of life in elderly patients with advanced cancer: a physical activity intervention of the multimodal nutrition and exercise treatment for advanced cancer program. Asia Pac J Oncol Nurs. 2018;5(4):383–390.30271820
   PubMed Web of Science ®Google Scholar
• Miura S, Naito T, Mitsunaga S, et al. A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol. BMC Cancer. 2019;19(1):528.31151425
   PubMed Web of Science ®Google Scholar
• Hall CC, Norris L, Dixon L, et al. A randomised, phase II, unblinded trial of an Exercise and Nutrition-based Rehabilitation programme (ENeRgy) versus standard care in patients with cancer: feasibility trial protocol. Pilot Feasibility Stud. 2018;27(4):192.
   Google Scholar
• 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(10):1059–1064.22880820
   PubMed Web of Science ®Google Scholar
• Baldwin C, Weekes CE. Dietary counselling with or without oral nutritional supplements in the management of malnourished patients: a systematic review and meta-analysis of randomised controlled trials. J Hum Nutr Diet. 2012;25(5):411–426.22672102
   PubMed Web of Science ®Google Scholar
• Temel JS, Greer JA, Goldberg S, et al. A structured exercise program for patients with advanced non-small cell lung cancer. J Thorac Oncol. 2009;4(5):595–601.19276834
   PubMed Web of Science ®Google Scholar
• Fearon K, Argiles JM, Baracos VE, et al. Request for regulatory guidance for cancer cachexia intervention trials. J Cachexia Sarcopenia Muscle. 2015;6(4):272–274.26675232
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Adlumiz: assessment Report. EMA/647868/2017; 9 14, 2017 Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/adlumiz Accessed 825, 2019.
   Google Scholar
• Gordon JN, Trebble TM, Ellis RD, et al. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut. 2005;54(4):540–545.15753541
   PubMed Web of Science ®Google Scholar
• Ramage MI, Skipworth RJE. The relationship between muscle mass and function in cancer cachexia: smoke and mirrors? Curr Opin Support Palliat Care. 2018;12(4):439–444.30138131
   PubMed Web of Science ®Google Scholar