Abstract

Background

This is an update of the orginal Cochrane review published on the 18th April 2012. 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

For this update we searched CENTRAL, MEDLINE, EMBASE, Web of Science and CINAHL (from ‐‐‐‐‐‐‐‐‐). Reference lists from reviewed articles, trial registers, relevant conference documents and thalidomide manufacturers were also searched.

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.

Author(s)

Joanne Reid, Moyra Mills, Marie M Cantwell, Chris R Cardwell, Liam J Murray, Michael Donnelly

Abstract

Plain language summary

Thalidomide for managing wasting syndrome (cachexia) in advanced cancer

This review aims to assess if thalidomide is an effective treatment for the wasting syndrome (know as cachexia) seen in patients with advanced cancer. However, there was not enough evidence to make an informed decision about the use of thalidomide for patients with advanced cancer who have this wasting syndrome. This means that thalidomide as a treatment for this wasting syndrome remains unproven and its use needs more testing. Additionally, this review highlighted that there may be undesirable side effects of thalidomide when used for this syndrome, which need to be looked at closely to ensure it is suitable for this group of patients.

Author(s)

Joanne Reid, Moyra Mills, Marie M Cantwell, Chris R Cardwell, Liam J Murray, Michael Donnelly

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Through conducting this systematic review we 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. Furthermore, the results from this systematic review suggest that there may be toxicities associated with thalidomide administration in this patient cohort that need to be explored further in light of the frailty of this population.

Implications for research 

Through conducting this systematic review, the lack of large RCTS is apparent. It is anticipated that the recent consensus on the clinical definition for cancer cachexia will help standardize inclusion criteria for future cachexia trials, as there was a degree of variability in the studies reviewed. Additionally, the majority of trials recruited patients who were extremely frail and at an advanced stage of their cancer trajectory, making if difficult to recruit sufficient numbers into studies and contributing to the high dropout rates. Up to 80% of cancer patients will have cachexia at an advanced stage (Murphy 2009) and it may be worth considering recruiting patients at an earlier juncture to see if potential treatment(s) would help prevent cachexia. It is also interesting to note that combination therapy for cancer cachexia has provided data on novel treatments and may be reflective of the multifaceted nature of this syndrome (Fearon 2008), and indeed its multidimensional impact on patients (Reid 2009a, Reid 2009b). 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. The number of patients who have this debilitating syndrome underscores the significance of this research direction.

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