Appraisal of current and experimental approaches to the treatment of cachexia.

PURPOSE OF REVIEW

To summarize the latest clinical developments in pharmacological interventions for primary cachexia.

RECENT FINDINGS

New orexigenic interventions that interfere with the central regulation of food intake are expected to be derived from the group of melanocortin receptor antagonists and ghrelin-mimetic agents. Emerging are muscle agents, including ubiquitin-proteasome system inhibitors, antimyostatin drugs, dystrophin, and beta2-adrenergic agonists. Results from anabolic steroids and angiotensin-II inhibitors are awaited. Recent data support insulin tackling fat metabolism. Branched-chain amino acids, N-3 fatty acids and conjugated linoleic acid are nutritional supplements that show potential. Adenosine 5'-triphosphate expands to related compounds (including ubiquinone). No breakthrough has occurred with the use of anti-inflammatory agents. Moreover, nonsteroidal anti-inflammatory drugs and thalidomide merit definitive studies. Presently modern anticytokine treatments lack proof of broad effectiveness. Some NF-kappaB inhibitors hold early promise. Melatonin requires placebo-controlled trials before recommendations on clinical use. Oxidative stress probably contributes to muscle wasting. L-Carnitine and other antioxidants appear promising. Anticancer treatments designed as anticachexia interventions remain scarce.

SUMMARY

A number of promising new agents are in development but are not yet regarded as standard of care. This void calls for well-designed, proof-of-concept studies followed by placebo-controlled, randomized trials.