Table 1 Study Characteristics of Clinical Trials focused on management of Cancer Cachexia (2005–2016)
Author, year, Study design | Number of patients | Cancer type | Definition of cachexia | Intervention | Study duration | Outcome measures | Results1 (Weight) (Anorexia-Cachexia Score) (LBM) | Results 2 (Appetite) | Results 3 (Functioning) | Results 4 (QOL-indicators) | Survival | Attrition/Completion Rate (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Group 1: Appetite Stimulants | ||||||||||||
 Strasser (2006) [22] RCT | 243 | Multiple | ≥5% loss of body weight | Arm1: CE Arm2: THC Arm3: PL | 6 weeks | Appetite (VAS) QOL (EORTC QLQ-C30) Body Weight | No differences on body weight or or Anorexia-Cachexia EORTC QLQ-C30 scores (p = NA) | No differences in appetite (VAS) scores between 3 groups (p = 0.46 and 0.95 respectively) | No significant differences on physical, role, emotional, cognitive, and social functioning | No differences in QOL indicators (p = 0.80 and 0.43 respectively) | N/A | 68 |
 Del Fabbro (2013) [24] RCT | 48 | Lung/GI | ≥5% loss of body weight | Arm1: Melatonin Arm2: Placebo | 28 days | Appetite change (ESAS) Body weight FACIT-F, Functional Assessment for Chronic Illness Therapy–Fatigue | NS (p = 0.17) | NS (p = 0.8) | No significant difference on FACIT Scale (p = 0.65) | No differences in scores on depression, wellbeing, pain and insomnia | N/A | 66 |
 Garcia (2015) [25] RCT | 82 | Multiple (mostly colon and lung) | ≥5% loss of body weight | Arm1: Anamorelin (50 mg) Arm2: Placebo | 12 weeks | LBM Handgrip strength ASAS score | Improvement in both lean body mass (p = 0.0006) and appendicular body mass (p = 0.006) in anamorelin as compared to placebo. No differences in fat mass. | Non-significant improvement (p = 0.36) | Handgrip Strength improved in A group as compared to P group (p = 0.014) | ASAS score improved in Anamorelin as compared to Placebo Group (p = 0.03) | N/A | 56 |
 Takayama (2016) [26] RCT | 181 | NSCLC | ≥5% loss of body weight | Arm1: Anamorelin (50 mg) Arm2: Anamorelin (100 mg) Arm3: Placebo | 12 weeks | LBM Handgrip strength QOL-ACD | Improved weight in anamorelin 50 and 100 mg (p = 0.02 and 0.0002) respectively as compared to placebo. Improvement in lean body mass (LBM) in both groups (P=NS) | Significant improvement in QOL-ACD appetite score for Anamorelin 100 mg as compared to placebo (p = 0.03) | No differences in handgrip strength across all groups. (p = NS) | Significant improvement in QOL-ACD total score in Anamorelin 100 mg as compared to placebo (p = 0.01) | NS (=0.08, for 100 mg, =0.70 for 50 mg) | 96 |
 Temel (2016) [27] RCT | ROMANA1: 484 ROMANA2: 495 | NSCLC | ≥5% loss of body weight or BMI < 20Kg/m2 | Arm1: Anamorelin (100 mg) Arm2: Placebo | 3 months | LBM Handgrip strength Anorexia-cachexia score | ROMANA1 Arm1: + 0.99 kg Arm2: -0.47 kg P = < 0.0001 ROMANA2 Arm1:+ 0.65 kg Arm2:-0.98 kg P = < 0.0001 | N/A | ROMANA1 Arm1:-1.10 kg Arm2:=1.58 kg P = 0.15 ROMANA2 Arm1:-1.49 kg Arm2:-0.95 kg P = 0.65 | ROMANA1 Arm1:4.12 Arm2:1.92 P = 0.0004 ROMANA2 Arm1:3.48 Arm2:1.34 P = 0.0016 | NS (p = 0.47) | 85 |
 Katakami (2018) [29] RCT | 172 | NSCLC | ≥5% loss of body weight | Arm 1: Anamorelin (100 mg) Arm 2: Placebo | 3 months | LBM (DEXA) Body weight Appetite Handgrip Strengh (Dynamometer) QOL (QOL-ACD) | Arm 1: + 1.06 kg Arm 2: −0.50 kg P < 0.0001 | Arm 1: + 0.7 Arm 2: + 0.3 P = 0.0005 | NS (p = 0.08) | Significant improvement in QOL in Arm 1 vs Arm 2(p = 0.02) | NS (p = 0.37) | 68 |
 Turcott (2018) [23] RCT | 47 | NSCLC | Based on AC/S of the Functional Assessment of Anorexia Cachexia Therapy (FAACT) tool | Arm 1: Nalibone (0.5 mg) Arm 2: Placebo | 2 weeks | Anorexia (FAACT) Appetite (VAS) QOL (EORTC-QOL-C30) | No difference (p = 0.72) | No difference (p = 0.21) | N/A | NS | NA | 70 |
Group 2: Cytokine Modulators | ||||||||||||
 Jatoi (2007) [32] RCT | 63 | Multiple (mostly lung and GI, exclude brain tumors) | 1.Weight loss (> 2.27 kg in 2 months) 2. Caloric intake< 20 cal/Kg of bw/day | Arm1: Etanercept 25 mg subcutaneous twice wkly Arm2: placebo | 24 weeks | 1. > 10% non-fluid weight gain from baseline 2. Appetite | Arm1: (0%) Arm2: (0%) (p = 0.35) | Appetite: (p = 0.87) | N/A | NS (p = NA) | NS (p = 0.82) | 95 |
 Jatoi (2010) [33] RCT | 61 | NSCLC | Age ≥ 65 years If < 65 years ECOG PS of 2 | Weekly docetaxel+ Arm1: Infliximab 5 mg/kg IV on day 1 and weeks 1, 3, 5 Arm2: placebo | 8 weeks | Non-fluid weight gain≥10% of baseline weight | Arm1 (0%) Arm2 (0%) NS (p = 0.17) | N/A | N/A | NS (p = NA) | NS (p = 0.88) | 65 |
 Gordon (2005) [34] RCT | 50 | Inoperable Pancreatic cancer | > 10% weight loss over 6 months | Arm1: Thalidomide Arm2: Placebo | 24 weeks | 1. Weight change(4wks) 2. Muscle mass 3. grip strength 4.QOL 5. Survival | Arm1:(+ 0.37Kg) Arm2:(−2.2Kg) (p = 0.005) | N/A | Grip strength Arm1:-0.88 Arm2:-1.00 (p = 0.9) | QOL: No difference (p = NA | NS (p = 0.45) | 66 |
 Yennurajalingam (2012) [35] RCT | 31 | Multiple (Mostly GI, GU) | ≥5% loss of body weight | Arm1: Thalidomide Arm2: Placebo | 2 weeks | Symptom assessment Functional assessment | NS (p = NA) | NS (p = NA) | N/A | NS (p = NA) | N/A | 60 |
 Mehrzad (2016) [36] RCT | 70 | Multiple | ≥5% loss of body weight | Arm1: Pentoxifylline Arm2: Placebo | 2 months | Body weight QOL | Arm1: Decreased Arm2: Decreased (p = 0.80) | N/A | N/A | Arm1: Decreased Arm2: Decreased (P = 0.037) | N/A | 91 |
Group 3: Anabolic Agents | ||||||||||||
 Lundholm (2007) [37] RCT | 138 | GI | 1. Weight loss (2–3% of referral weight) 2.Albumin< 36 g/L | Arm1:Insulin (0.11+/−0.05 units/kg/d) + BSC Arm2:BAS (no placebo) | Variable | 1. Body composition 2. Physical activity 3. QOL | NS (p = NA) | NS (p = NA) | NS (p = NA) | NS (p = NA) | Significant Arm1: 181 days Arm2:128 days P < 0.03 | NA |
 Dobs (2013) [38] RCT | 159 | Multiple (Mostly lung, colorectal) | ≥2% loss of body weight | Arm1: Enobosarm 1 mg Arm2: Enobsoarm 3 mg Arm3: Placebo | 113 days | LBM Physical activity (Stair climb time) QOL (FAACT) | Arm1: Increased (p = 0.0012) Arm2: Increased (p = 0.046) Arm3: No change (p = 0.88) | N/A | Arm1:Improved(p = 0.0019) Arm2: Improved(p = 0.0065) Arm3: No change (p = 0.11) | Arm1: (P = 0.007) Arm2: (p = 0.14) Arm3: (p-0.41) | NS | 63 |
Group 4: Combination Agents | ||||||||||||
 Wen (2012) [41] RCT | 102 | Multiple (Mostly lung, gastric) | ≥5% loss of body weight | Arm1:MA + thalidomide Arm2: MA | 8 weeks | Body weight Fatigue QOL Grip strength | NS (=p = 0.05) | NS (p = 0.12) | NS (p = 0.05) | Sig (p < 0.01) | N/A | 91 |
 Kanat (2013) [42] RCT | 62 | Multiple | ≥5% loss of body weight | Arm1:MA + Meloxicam Arm2:MA + Meloxicam+EPA Arm3: Meloxicam+EPA | 3 months | LBM BMI QOL | NS (p = 0.61) | N/A | N/A | NS (p = NA) | N/A | TBD |
 Mantovani (2010) [43] RCT | 332 | Multiple (Mostly lung, breast, colon) | Weight loss > 5% | Arm1: MPA or MA Arm2: EPA supplement Arm3: L-Carnitine Arm4: Thalidomide Arm5: combination | 4 months | 1.LBM (DEXA) Grip strength QOL (EQ-5D) | Arm3:(−0.7 kg) Arm4:(−0.8 kg) Arm5: (2.1 kg) (P .007) | Significant improvement in arm 5.(p = 0.0037) | NS (p = NA) | NS (p = NA) | NS (p = NA) | 100 |
 Madeddu (2012) [44] RCT | 60 | Multiple (Mostly head & neck, lung) | ≥5% loss of body weight | Arm1: L-Carnitine + Celecoxib Arm2: L-Carnitine + Celecoxib + MA | 4 months | LBM Physical activity | NS(p = 0.33) | NS (=0.25) | NS(p = 0.08) | NS (p = 0.51) | NS (p = NA) | 93 |
 Kouchaki (2018) [45] RCT | 60 | GI | > = 5% loss of body weight, 2 years of life expectancy | Arm 1: Celecoxib+MA Arm 2: MA | 2 months | Body Weight (> = 5%) Appetite (VAS) Grip strength QOL (EORCT QOL-C30) | NS (0.83) | NS (p = 0.05) | NS (p = 0.36) | NS (p = 0.25) | NS (p = NA) | 37 |