Non‐steroidal anti‐inflammatory drugs for treatment of cancer cachexia: A systematic review

Abstract

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 non‐steroidal anti‐inflammatory drugs (NSAIDs) on patient‐centred outcomes in patients with CC. In 2013, two systematic reviews concluded that 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. Four databases (MEDLINE, EMBASE, CENTRAL and CINAHL) and three trial registers (clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched on 16 December 2022. Randomized 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. 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 is 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 (200–400 mg/day) but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies. There is inadequate evidence to recommend any NSAID for CC. While 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.

Harnessing the Systemic Biology of Functional Decline and Cachexia to Inform more Holistic Therapies for Incurable Cancers

“…The use of anti-inflammatories within a multi-disciplinary intervention has been proposed, although their overall efficacy remains unclear [129]. In one study of indomethacin treatment, cancer patients increased median survival from 250 days to 510 days [130], but more recent studies have demonstrated that the role of NSAIDs in treating cachexia is unclear and further study is still needed [131]. Corticosteroids have demonstrated improved body weight and appetite in cancer cachexia patients; however, treatment is recommended to last no more than a few weeks due to accumulated toxicity and side effects with long-term use.…”