Non-steroidal anti-inflammatory drugs for treatment of cancer cachexia: a systematic review

Background: Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) on patient-centred outcomes in patients with CC. In 2013, two systematic reviews concluded there was insufficient evidence to recommend NSAIDs for clinical management of CC outside of clinical trials. However, clinical trials of multi-component CC interventions have included NSAIDs as an intervention component, so an up-to-date assessment of the evidence for NSAIDs in the treatment of CC is warranted.

Methods: Four databases (MEDLINE, EMBASE, CENTRAL, CINAHL) and three trial registers(clinicaltrials.gov, WHO ICTRP, ISRCTN) were searched on 16/12/2022. Randomised Controlled Trials (RCTs) comparing any NSAID (any dose or duration) with a control arm, in adult patients with CC, reporting measures of body weight, body composition, nutrition impact symptoms, inflammation, physical function, or fatigue, were eligible for inclusion. Primary outcomes (determined with patient involvement) were survival, changes in muscle strength, body composition, body weight and quality of life. Included studies were assessed for risk of bias using the Revised Cochrane risk-of-bias tool for randomized trials.

Results: Five studies were included, which investigated Indomethacin (n=1), Ibuprofen (n=1)and Celecoxib (n=3). Four studies were judged to be at high risk of bias for all outcomes, with one study raising concerns for most outcomes. Considerable clinical and methodological heterogeneity amongst the studies meant that meta-analysis was not appropriate. There was insufficient evidence to determine whether Indomethacin or Ibuprofen are effective or safe for use in patients with CC; RCTs with lower risk of bias are needed. Celecoxib studies indicated it was safe for use in this population at the doses tested (200-400mg/day), but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies.

Conclusions: There is inadequate evidence to recommend any NSAID for CC. Whilst current clinical trials for CC treatments are shifting towards multi-component interventions, further research to determine the efficacy and safety of NSAIDs alone is necessary if they are to be included in such multi-component interventions. Furthermore, the lack of data on patient-determined primary outcomes in this review highlights the need for patient involvement in clinical trials for CC.