Appetite Stimulants May Provide the Most Rapid Improvement in Cachexia

No safety signals were raised in a network-meta-analysis comparison of pharmacologic agents for cachexia at the specified period of analysis

Findings from a network-meta-analysis assessing the relative efficacy and safety of 12 pharmacologic interventions for cachexia were presented at the ESMO Asia 2017 in Singapore, an Annual Congress organised by the European Society for Medical Oncology.

Manit Sae-Teaw, Pharmacy Practice, Ubon Ratchathani University, Ubon Ratchathani, Thailand noted that comparative head to head information on the efficacy and safety of agents used in recent clinical trials is not available, leading Professor Sae-Teaw and colleagues to compare the weight and appetite improvement provided by various pharmacologic interventions for cachexia in this network meta-analysis.

The investigators performed a systematic review of PubMed, EmBase, Cochrane, and ClincalTrials.gov databases for randomised clinical trials (RCTs) reporting key outcomes of total body weight (TBW) improvement, and improved appetite (APP) scores, as well as serious adverse events.

The data were reviewed and the risk of bias of all RCTs was assessed by two independent researchers. The meta-analysis estimated relative magnitude of weight gain and appetite score increase within 8 weeks of administration of all interventions, which were reported as mean difference (MD) or standardized mean difference with 95% confidence interval (CI). To rank the intervention hierarchy in the network meta-analysis, the rankograms, surface under the cumulative ranking (SUCRA) curves, and mean ranks were estimated.

The meta-analysis included data from 9,615 patients participating in73 RCTs, of these patients, 6,335 were cancer patients and 2,324 were HIV patients.

Improved weight gain was seen with corticosteroids but appetite stimulants showed the quickest appetite improvement scores

Twelve therapeutic cachexia interventions were evaluated and compared. Regarding improved total body weight, corticosteroids, Megestrol acetate-High dose (>400 mg) combination, Megestrol acetate-High dose (>400 mg), and androgen were significantly associated with mean differences of 6.23 (95% CI 1.91, 10.56), 3.73 (95% CI 1.58, 5.88), 2.80 (95% CI 1.46, 4.13), and 1.47 (95%CI 0.31, 2.63) kilograms compared to placebo, respectively. Nonetheless, the highest benefit of corticosteroid in improving weight gain has been demonstrated from only one clinical trial using prednisolone 20 mg/day without survival improvement. Therefore, longer follow up is required for long term corticosteroid use to ascertain optimal risk/benefit ratio.

Regarding appetite improvement, significantly improved standardized mean different appetite scores were observed with Megestrol acetate-Low dose, Megestrol acetate-High dose, medroxyprogesterone, androgen, Megestrol acetate-High dose combination, and ghrelin mimetics, compared to placebo. With the appetite stimulants ghrelin, Megestrol acetate-Low dose, Megestrol acetate-High dose, and medroxyprogesterone score improvements were reported earlier than 8 weeks.

The investigators observed no significant difference in serious adverse drug reactions with any of these agents compared to the placebo at 8 weeks analysis.

Conclusions

Findings from this network meta-analysis suggest that appetite stimulants may offer superior benefits in the treatment of cachexia. However, the authors encourage that comparative studies directly comparing safety and efficacy are warranted to optimise cachexia management.

Disclosure

No external funding was reported.

Reference

502O – Saw-Teaw M, et al. Comparative efficacy and safety of Pharmacologic interventions for cachexia: A systematic review and network meta-analysis.