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

Figures & data

Figure 1 Skeletal muscle metabolism and clinical outcomes in cancer cachexia.

Abbreviations: TNF, tumor necrosis factor; IL, interleukin; QOL, quality of life.

Table 1 Trials Of Anamorelin Hydrochloride In Patients With Cancer Cachexia

Publication	N	Study Population Cancer Types (Cachectic Status^a)	Concurrent Cancer Treatment	Trial Arms (Intervention Period)	Major Outcomes For Anamorelin 1. Positive 2. Negative	Major Toxicity
Garcia et al, Support Care Cancer. 2013^Citation45	16	Mixed advanced cancer (Cachexia)	Not specified or combined	Anamorelin vs placebo (3 days)	1. BW, Appetite 2. Food intake	Hyperglycemia
Garcia et al, Lancet Oncol. 2015^Citation46	44	Mixed advanced cancer (Cachexia)	Not specified or combined	Anamorelin vs placebo (12 weeks)	1. LBM, BW, QOL 2. HGS	Not specified
Takayama et al, Support Care Cancer. 2016^Citation47	181	Advanced NSCLC in Japanese (Cachexia)	Not specified or combined	Anamorelin vs placebo (12 weeks)	1. LBM, BW, PS, QOL, Anorexia 2. HGS	Nausea, Increased glycosylated hemoglobin
Temel et al, Lancet Oncol. 2016 (ROMANA 1 and 2)^Citation49	979	Advanced NSCLC (Cachexia)	Not specified or combined	Anamorelin vs placebo (12 weeks)	1. LBM, BW, Anorexia-cachexia symptoms 2. HGS, Fatigue	Not specified
Currow et al, Ann Oncol. 2017 (ROMANA 3)^Citation50	513	Advanced NSCLC: Completers of ROMANA 1 or 2 (Cachexia)	Not specified or combined	Anamorelin vs placebo (24 weeks)	1. BW, Anorexia-cachexia symptoms 2. HGS	Not specified
Katakami et al, Cancer. 2018^Citation48	174	Advanced NSCLC in Japanese (Cachexia)	Not specified or combined	Anamorelin vs placebo (24 weeks)	1. LBM, BW, Anorexia 2. HGS, 6MWD, Fatigue	Atrioventricular block, rash
Hamauchi et al, Cancer. 2019^Citation51	50	Advanced gastrointestinal cancer in Japanese (Cachexia)	Not specified or combined	Anamorelin (12 weeks)	Single-arm study with pre-post comparison 1. LBM, BW, Appetite 2. Not specified	Not specified
Nishie et al, Lung Cancer. 2017^Citation52	1641	Mixed advanced cancers in 6 RCTs for meta-analysis including reference 2, 3, 4, and 6 (Cachexia)	Not specified or combined	Anamorelin vs placebo (12 weeks)	In the meta-analysis, 1. LBM, BW, QOL 2. HGS, OS, Appetite	Not specified
Bai et al, Support Care Cancer. 2017^Citation53	1168	Mixed advanced cancers in 4 RCTs for meta-analysis including reference 1, 2, 3, and 4 (Cachexia)	Not specified or combined	Anamorelin vs placebo (3 days or 12 weeks)	In the meta-analysis, 1. LBM, BW, QOL 2. HGS	Not specified

Notes: ^aCachectic status was classified into precachecia, cachexia, refractory cachexia, or high risk for cachexia according to the consensus report.⁴

Abbreviations: BW, body weight; LBM, lean body mass; HGS, hand-grip strength; QOL, quality of life; NSCLC, non-small-cell lung cancer; PS, performance status; 6MWD, 6-min walk distance; RCT, randomized controlled trial; OS, overall survival.

Table 2 Trials Of Multidrug Combinations In Patients With Cancer Cachexia

Publication	N	Study Population Cancer Types (Cachectic Status^a)	Concurrent Cancer Treatment	Trial Arms (Intervention Period)	Major Outcomes 1. Positive 2. Negative	Major Toxicity
Jatoi et al, J Clin Oncol. 2004^Citation67	421	Mixed advanced cancer (Cachexia)	Not specified or combined	EPA vs MA vs MA + EPA (4 weeks)	In the MA containing regimens as compared with EPA 1. BW, Appetite 2. QOL, OS	Not specified
Mantovani et al, Oncologist. 2010^Citation64	332	Mixed advanced cancer (Cachexia)	Not specified or combined	Progestational agent vs EPA vs L-Carnitine vs Thalidomide vs Combination of all agents (4 months)	In the combination arm as compared with other 4 arms 1. LBM, PS, GPS, REE, Fatigue, Appetite, Physical activity 2. QOL	Not specified
Wen et al, Chemotherapy. 2012^Citation65	102	Mixed advanced cancer (Cachexia)	Not specified or combined	MA vs MA + Thalidomide (8 weeks)	In the combination arm as compared with MA 1. BW, HGS, PS, QOL, GPS, Fatigue 2. None	Not specified
Macciò et al, Gynecol Oncol. 2012^Citation66	104	Advanced gynecological tumor (Cachexia)	Not specified or combined	MA vs MA + L-carnitine, celecoxib, and antioxidants (4 months)	In the combination arm as compared with MA 1. LBM, QOL, REE, Fatigue 2. PS, GPS, Appetite	Not specified
Madeddu et al, Clin Nutr. 2012^Citation68	60	Mixed advanced cancer (Cachexia)	Not specified or combined	Arm 1 (L-carnitine + celecoxib) vs Arm 2 (L-carnitine + celecoxib + MA) (4 months)	In the arm 2 as compared with arm 1 1. None 2. LBM, BW, HGS, 6MWD, QOL, REE, Appetite, Fatigue	Not specified
Kouchaki et al, Support Care Cancer. 2018^Citation69	90	Mixed gastrointestinal cancer (Cachexia)	Majority in chemotherapy	Arm 1 (MA + placebo) vs Arm 2 (MA + celecoxib) (2 months)	In the arm 2 as compared with arm 1 1. None 2. BW, QOL, HGS, Appetite, PS, GPS	Not specified

Notes: ^aCachectic status was classified into precachecia, cachexia, refractory cachexia, or high risk for cachexia according to the consensus report.⁴

Abbreviations: EPA, eicosapentaenoic acid; MA, megestrol acetate; BW, body weight; QOL, quality of life; OS, overall survival; LBM, lean body mass; PS, performance status; GPS, Glasgow Prognostic Score; REE, resting energy expenditure; HGS, hand-grip strength; 6MWD, 6-min walk distance.

Table 3 Trials Of Multimodal Interventions For Patients With High-Risk For Cancer Cachexia

Publication	N	Study Population Cancer Types (Cachectic Status^a)	Concurrent Cancer Treatment	Trial Arms (Intervention Period)	Major Outcomes 1. Positive 2. Negative	Major Toxicity (Compliance)
Solheim et al, J Cachexia Sarcopenia Muscle. 2017 (Pre-MENAC study)^Citation81	46	Advanced pancreatic or lung cancer (High-risk for cachexia)	Palliative chemotherapy	Exercise + Nutritional advice + ONS + NSAID vs Usual care ONS: Prosure^®, rich in EPA (6 weeks)	In the multimodal intervention arm as compared with usual care arm 1. BW 2. LBM, HGS, 6MWD, Physical activity, Nutritional status, Fatigue, OS	Not specified (>50% compliance for all components was 12% (3/25) in the treatment arm)
Uster et al, Clin Nutr. 2018^Citation83	58	Advanced gastrointestinal or lung cancer (High-risk for cachexia)	Not specified or combined	Exercise + Nutritional advice + ONS vs Usual care ONS: Protein-rich ONS (3 months)	In the multimodal intervention arm as compared with usual care arm 1. Nausea and vomiting, Protein intake 2. LBM, BW, HGS, 6MWD, sit-to-stand, leg strength, QOL	Not specified (Mean attendance of 67% in all sessions)
Solheim et al, BMJ Support Palliat Care. 2018 (MENAC study)^Citation82 Trial registration: NCT02330926	240	Advanced pancreatic or lung cancer (High-risk for cachexia)	Not specified or combined	Exercise + Nutritional advice + ONS + NSAID vs Usual care ONS: Prosure^®, rich in EPA (6 weeks)	Ongoing trial Status: Recruiting Start date: Jan 2015 Primary endpoint: BW Secondary endpoints: Muscle mass, Physical activity
Hall et al, Pilot Feasibility Stud. 2018^Citation88	40	Mixed advanced cancer (High-risk for cachexia)	Palliative care	Exercise + nutritional advice + ONS vs Usual care ONS: EPA-rich ONS (8 weeks)	Ongoing trial Status: on going Start date: Jan 2018 Primary endpoint: Compliance Secondary endpoints: BW, PS, 2-min walk test, Timed up and go test, QOL
Miura et al, BMC Cancer. 2019 (NEXTAC-TWO study)^Citation87 Trial registration: UMIN000028801	130	Elderly patients with advanced pancreatic or lung cancer (High-risk for cachexia)	Palliative chemotherapy	Exercise + Physical activity promotion + Nutritional advice + ONS vs Usual care ONS: Inner Power^®, rich in branched chain amino acids (12 weeks)	Ongoing trial Status: On follow-up period until Mar 2021 (Enrollment completed) Start date: Nov 2017 Primary endpoint: Disability-free survival Secondary endpoints: BW, Muscle mass, HGS, SPPB, QOL

Notes: ^aCachectic status was classified into precachecia, cachexia, refractory cachexia, or high risk for cachexia according to the consensus report.⁴

Abbreviations: ONS, oral nutritional supplement; NSAID, nonsteroidal anti-inflammatory drug; EPA, eicosapentaenoic acid; BW, body weight; LBM, lean body mass; HGS, hand-grip strength; 6MWD, 6-min walk distance; OS, overall survival; QOL, quality of life; PS, performance status; SPPB, short physical performance battery.

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