Yavuzsen, T., Davis, M.P., Walsh, D., LeGrand, S., & Lagman, R. (2005). Systematic review of the treatment of cancer-associated anorexia and weight loss. Journal of Clinical Oncology, 23, 8500–8511.

DOI Link

Search Strategy

Studies were included in the review if they reported on

  • Adult patients older than 18 years of age
  • Patients with nonhematologic malignancies
  • Patients with anorexia or symptoms of anorexia, such as lack of appetite, weight loss, poor performance status, and decreased quality of life.

Literature Evaluated

The review involved only prospective, randomized controlled trials (RCTs; double- and single-blind or unblended and phase III trials). The quality of studies was assessed using the validated scale published by Jadad et al. (1996).

Sample Characteristics

There were 55 studies reviewed that met the eligibility criteria.

Results

Androgenic steroids
Androgenic steroids were studied in two studies involving 512 patients; no significant benefit was demonstrated.
 
Cannabinoids
Cannabinoids were studied in one RCT involving 469 patients; they did not confer an additional benefit.
 
Corticosteroids
Six studies investigated the use of corticosteroids in 647 patients. Some improvements in appetite were found; however, dosage and type of steroid varied such that optimal dose and duration of therapy could not be determined.
 
Cyproheptadine
Two studies investigated the use of cyproheptadine in 344 patients; these investigations had conflicting outcomes.
 
Eicosapentaenoic acid (EPA)
Three studies investigated the use of EPA in 689 patients; these reported conflicting results.
 
Erythropoietin (EPO)
EPO was investigated in two studies involving 417 patients. In one investigation, EPO was administered in combination with a COX-2 inhibitor with and without a specialized nutritional program. The intent-to-treat analysis was negative. No differences in food intake were noted.
 
Ghrelin
Ghrelin was investigated in one RCT involving seven patients; differences between groups were noted, but long-term safety data on the agent are not available.
 
Hydrazine sulfate
Five studies investigated the use of hydrazine sulfate in 796 patients. Multicenter RCTs in patients with lung and colon cancers did not demonstrate any benefit when compared to a placebo.
 
Interferon
Interferon was investigated in one study involving 57 patients; no differences were found.
 
Melatonin
Melatonin was investigated in two studies involving 186 patients; they did not demonstrate any improvement in appetite or intake.
 
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs were investigated in two trials involving 417 patients; these investigations failed to demonstrate a benefit in the NSAID arm.
 
Pentoxyfilline
One study investigated the use of pentoxyfilline in 70 patients and found no benefit. Melatonin was investigated in two studies involving 186 patients; these did not demonstrate any improvement in appetite or intake.
 
Progestins
Twenty-nine studies reviewed the safety and efficacy of progestins: 23 examined megesterol acetate (MA), and six investigated medroxyprogesterone acetate (MPA). Results favored progestins over placebo and found that side effects were tolerable. Ten studies assessed the influence of MA on quality of life; these demonstrated that the effect of MA on quality of life was minimal.
 
Prokinetics
Two studies investigated prokinetics for anorexia in a total of 55 patients. No improvement in caloric intake or appetite was noted.
 
Thalidomide
Thalidomide has not been investigated in prospective RCTs.

Conclusions

Multiple RCTs have been conducted to investigate the safety and efficacy of pharmacologic agents to stimulate appetite. Only two therapeutic interventions for cancer-related anorexia demonstrated enough evidence to support their use in patients with cancer: corticosteroids and progestins. Other studies had mixed outcomes, positive results in only a single randomized trial, or were not placebo-controlled.

There is strong evidence supporting the use of progestins in patients with cancer, of which the most commonly reported drugs were MA and MPA. There was increased weight with both progestins; there was also evidence of a dose-response, but higher doses did not confer any additional benefit with regard to appetite. Metaclopromide is effective for nausea and early satiety but has not been shown to directly stimulate appetite.

The RCTs did not show sufficient evidence to justify the use of dronabinol, EPA, EPO, ghrelin, interferon, melatonin, nandrolone, NSAIDs, or pentoxyfilline in cancer-related anorexia. Cyproheptadine is a weak appetite stimulant, but side effects are limiting.

Nursing Implications

The optimal dose, start time, and duration of treatment for many appetite stimulants are still unknown. A more systematic approach to research methodology is needed. In addition, uniform outcome measures to better assess the value of various appetite stimulants are needed. These should include subjective ratings of appetite and associated symptoms (e.g.,  early satiety) and objective measures (e.g., food consumed, weight gain, weight loss).

Legacy ID

1304