Table 1.
Table summarizing unimodal treatment options mentioned in this review.
| Drug name | Drug class | Molecule type | Disease | Status | Positive outcomes | Adverse effects/Difficulties | References |
|---|---|---|---|---|---|---|---|
| Etanercept | Anti-TNFα therapy | TNFα receptor-blocker | Cancer (other than brain cancer) | Phase III RCT (placebo) | – | Induced negligible weight gain; did not improve median survival; caused higher rates of neurotoxicity. | NCT00046904 (161) |
| Thalidomide | Anti-TNFα therapy | Synthetic derivative of glutamic acid | Pancreatic cancer | RCT (placebo) | Attenuated weight and lean body mass losses | No significant improvements of QoL | (162) |
| Thalidomide | Anti-TNFα therapy | Synthetic derivative of glutamic acid | Cancer | Phase III RCT | Significant decrease in levels of circulating IL-6; did not cause worsening of life | Lack of satisfactory documentation | (163) |
| Thalidomide | Anti-TNFα therapy | Synthetic derivative of glutamic acid | Cancer | RCT (placebo) | Slight decrease in levels of circulating IL-6 and TNFα | No significant benefits compared with placebo; possible risk of treatment-related mortality | (164) |
| Pentoxifylline | Anti-TNFα therapy | Methylxanthine derivative | Cancer (other than brain cancer) | RCT (placebo) | – | No differences in QoL and possible worsening of life after 4 weeks of treatment | (165) |
| Pentoxifylline | Anti-TNFα therapy | Methylxanthine derivative | Cancer | RCT (placebo) | No toxicity | Did not improve appetite nor significant weight gain | (166) |
| Infliximab | Anti-TNFα therapy | Chimeric IgG1k monoclonal antibody | NSCLC | Phase III RCT (placebo)/ docetaxel | – | Did not induced weight gaining; caused increased fatigue and inferior global QoL | NCT00040885 (167) |
| Clazakizumab | Anti-IL6 therapy | Humanized anti-IL-6 monoclonal antibody | Cancer | Phase I CT | No apparent toxicity; increased hemoglobin and albumin levels; reduced fatigue | Lack of satisfactory documentation | (168) |
| Clazakizumab | Anti-IL6 therapy | Humanized anti-IL-6 monoclonal antibody | NSCLC | Phase II RCT | Generally well tolerated; improved the lung symptom score; attenuated lean mass loss; reversed fatigue | May cause rectal hemorrhage or treatment-related mortality in a minority of patients; inconclusive in terms of clinical management | NCT00866970 (169) |
| Selumetinib | Anti-IL6 therapy | MEK1/2 inhibitor | Biliary cancer | Phase II CT | Overall acceptable tolerability; induced significant weight gaining | Induced low-grade adverse events including rush and xerostomia; may worsen fatigue in a minority of patients | NCT00553332 (170) |
| Selumetinib | Anti-IL6 therapy | MEK1/2 inhibitor | Cholangiocarcinoma | Phase II CT | Induced significant gaining of lean body mass | Lack of satisfactory documentation | (22) |
| Ruxolitinib | Anti-IL6 therapy | JAK1/2 inhibitor | Cancer | Phase II CT | – | The study was terminated due to poor recruiting | NCT02072057 |
| Xilonix | Anti-IL-1α therapy | IL-1α-specific humanized monoclonal antibody | Cancer | Phase I CT | Well tolerated by all participants, no dose-limiting toxicities were reported | Caused proteinuria, anemia, nausea and fatigue in a minor fraction of patients | NCT01021072 (171) |
| Xilonix | Anti-IL-1α therapy | IL-1α-specific humanized monoclonal antibody | CRC | Phase III RCT (placebo) | Prevented alteration of body composition and improved control of thrombocytosis | Caused proteinuria, anemia, increased concentration of alkaline phosphatase and aspartate aminotransferase and fatigue in a minor fraction of patients | NCT01767857 (172) |
| Xilonix | Anti-IL-1α therapy | IL-1α-specific humanized monoclonal antibody | CRC | Phase III CT | – | The study was stopped as it crossed the prospective futility boundary of primary endpoint | NCT01767857 |
| Celecoxib | NSAID | Cyclooxygenase-2 (COX-2) inhibitor | Cancer | Phase II RCT (placebo) | Significantly improved BMI and QoL; moderate decrease of IL-6 levels after 3 weeks of treatment | – | (173) |
| Celecoxib | NSAID | Cyclooxygenase-2 (COX-2) inhibitor | Cancer | Phase II CT | Significantly improved BMI and QoL; moderate decrease of TNFα levels; increased handgrip strength and improved performance status | – | (174) |
| LY2495655 | Mstn inhibition | Monoclonal antibody to Mstn | (1) Cancer (2) Healthy | (1) Phase I RCT (placebo) (2) Phase I CT | Well tolerated; no dose-limiting toxicities were reported; increase in thigh muscle volume; consistent increases in handgrip strength observed at doses ≥21 mg; improvement in functional measures | No clear trend in dose-dependent efficacy | NCT01524224 (175) |
| LY2495655 | Mstn inhibition | Monoclonal antibody to Mstn | Pancreatic cancer | Phase II RCT (placebo) + standard chemotherapy | – | No significant improvements in muscle volume; pre-cachectic patients were more responsive than cachectic patients; trend toward poorer overall survival in treated patients vs. placebo | NCT01505530 (176) |
| Bimagrumab | Mstn inhibition | Human monoclonal anti-ActRII antibody | NSCLC and Pancreatic adenocarcinoma | Phase II RCT (placebo) | Significant increase in lean body mass and thigh muscle volume | Significant decrease in total body weight | NCT01433263 |
| AMG 745 | Mstn inhibition | Fc fusion peptibody | Prostate cancer | Phase I RCT (placebo) | Generally well tolerated; increased lean body mass | Slight decrease in fat mass; may cause adverse events including diarrhea and fatigue | NCT00975104 (177) |
| Megestrol acetate (FDA approved) | Appetite stimulant | Progesteron derivative | Several cancer types | Summary of 35 CT | Improvement of appetite and increased caloric intake, weight gain and nutritional status; improvement of QoL; downregulation of proinflammatory cytokines or that of their cognate receptors | More than 40 side effects including edema, thromboembolitic episodes and treatment-related death | Summary of 35 clinical trials (178) |
| Medroxyp rogesterone acetate (FDA approved) | Appetite stimulant | Progesteron derivative | Several cancer types | Summary of most relevant CT | Improved anorexia and QoL parameters; impaired synthesis and release of IL-6, IL-1, and TNFα | Weight gain was due to increased body fat mass rather than lean body mass | Summary of most relevant clinical trials (179) |
| Ghrelin | Orexigenic mediator | Hormone | Esophageal cancer | Phase II RCT (placebo) + cisplatin-based neoadjuvant chemotherapy | Increased food consumption and weight gain; reduced nausea and anorexia related to chemotherapy | – | (180) |
| Anamorelin HCl | Orexigenic mediator | Ghrelin Receptor agonist | NSCLC | Phase III | Generally well tolerated; improved appetite; increased food intake, body weight and lean body mass | Caused hyperglycemia, nausea and gastrointestinal disorders in a minority of patients; no significant improvement of handgrip strength | NCT01387269 (181) |
| Anamorelin HCl | Orexigenic mediator | Ghrelin Receptor agonist | NSCLC | Phase III | Generally well tolerated; improved appetite; increased food intake, body weight and lean body mass | Caused hyperglycemia, nausea and gastrointestinal disorders in a minority of patients; no significant improvement of handgrip strength | NCT01387282 (181) |
| Anamorelin HCl | Orexigenic mediator | Ghrelin Receptor agonist | NSCLC | Phase III | Generally well tolerated; improved appetite; increased food intake, body weight and lean body mass | Caused hyperglycemia, nausea and gastrointestinal disorders in a minority of patients; no significant improvement of handgrip strength | NCT01395914 (182) |
| THC | Appetite stimulant and metabolism modulator | Endogenous agonist of CB1 and CB2 receptors | Cancer | Phase III CT | Well tolerated, no adverse effects | No significant improvements in appetite or QoL | (183) |
| THC | Appetite stimulant and metabolism modulator | Endogenous agonist of CB1 and CB2 receptors | Cancer | Phase III CT | Well tolerated, no adverse effects; significant increase in appetite and caloric intake; improved chemosensory perception and QoL | – | NCT00316563 (184) |
| THC | Appetite stimulant and metabolism modulator | Endogenous agonist of CB1 and CB2 receptors | Cancer | Pilot study | Well tolerated; significant increase in appetite and caloric intake; improved QoL; reversed fatigue | May induce dizziness or anxiety in a small fraction of patients | NCT02359123 (185) |
| Nabilone | Appetite stimulant and metabolism modulator | Synthetic analog of THC | NSCLC | Phase II RCT (placebo) | Increased appetite and caloric intake; improvement of QoL; attenuated pain and insomnia | – | NCT02802540 (186) |
| Erythropoietin | Anemia reversal | Hormone | Cancer | Randomized study | Reversed anemia; improved exercise ability and sense of well-being | No significant improvements in QoL; discrepancies between objective and subjective self-reported measures | (187) |
CT, clinical trial; RCT, randomized clinical trial.