Thalidomide for managing cancer cachexia

Abstract

Background: Cancer cachexia is a multidimensional syndrome characterised by wasting, loss of weight, loss of appetite, metabolic alterations, fatigue and reduced performance status. A significant number of patients with advanced cancer develop cachexia before death. There is no identified optimum treatment for cancer cachexia. While the exact mechanism of the action of thalidomide is unclear, it is known to have immunomodulatory and anti-inflammatory properties, which are thought to help reduce the weight loss associated with cachexia. Preliminary studies of thalidomide have demonstrated encouraging results. Objectives: This review aimed to (1) evaluate the effectiveness of thalidomide, and (2) identify and assess adverse effects from thalidomide for cancer cachexia. Search methods: Electronic searches were undertaken in CENTRAL, MEDLINE, EMBASE, Web of Science and CINAHL (from inception to April 2011). Reference lists from reviewed articles, trial registers, relevant conference documents and thalidomide manufacturers identified additional literature. Selection criteria: This review included randomised controlled trials (RCTs) and non-RCTs. Participants were adults diagnosed with advanced or incurable cancer and weight loss or a clinical diagnosis of cachexia who were administered thalidomide. Data collection and analysis: All titles and abstracts retrieved by electronic searching were downloaded to a reference management database. Duplicates were removed and the remaining citations were read by two review authors and checked for eligibility. Studies that were deemed ineligible for inclusion had clear reasons for exclusion documented. Data were extracted independently by two review authors for all eligible studies. While a meta-analysis was planned for this review, this was not possible due to the small number of studies included and high heterogeneity among them. Thus a narrative synthesis of the findings is presented. Main results: The literature search revealed a dearth of large, well conducted trials in this area. This has hindered the review authors' ability to make an informed decision about thalidomide for the management of cancer cachexia. At present, there is insufficient evidence to refute or support the use of thalidomide for the management of cachexia in advanced cancer patients. Authors' conclusions: The review authors cannot confirm or refute previous literature on the use of thalidomide for patients with advanced cancer who have cachexia and there is inadequate evidence to recommend it for clinical practice. Additional, well conducted, large RCTs are needed to test thalidomide both singularly and in combination with other treatment modalities to ascertain its true benefit, if any, for this population. Furthermore, one study (out of the three reviewed) highlighted that thalidomide was poorly tolerated and its use needs to be explored further in light of the frailty of this population.