Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial

Abstract

Background: Proinflammatory cytokines, especially tumour necrosis factor a (TNF-a), play a prominent role in the pathogenesis of cancer cachexia. Thalidomide, which is an inhibitor of TNF-a synthesis, may represent a novel and rational approach to the treatment of cancer cachexia. Aims: To assess the safety and efficacy of thalidomide in attenuating weight loss in patients with cachexia secondary to advanced pancreatic cancer. Methods: Fifty patients with advanced pancreatic cancer who had lost at least 10% of their body weight were randomised to receive thalidomide 200 mg daily or placebo for 24 weeks in a single centre, double blind, randomised controlled trial. The primary outcome was change in weight and nutritional status. Results: Thirty three patients (16 control, 17 thalidomide) were evaluated at four weeks, and 20 patients (eight control, 12 thalidomide) at eight weeks. At four weeks, patients who received thalidomide had gained on average 0.37 kg in weight and 1.0 cm 3 in arm muscle mass (AMA) compared with a loss of 2.21 kg (absolute difference 22.59 kg (95% confidence interval (CI) 24.3 to 20.8); p = 0.005) and 4.46 cm 3 (absolute difference 25.6 cm 3 (95% CI 28.9 to 22.2); p = 0.002) in the placebo group. At eight weeks, patients in the thalidomide group had lost 0.06 kg in weight and 0.5 cm 3 in AMA compared with a loss of 3.62 kg (absolute difference 23.57 kg (95% CI 26.8 to 20.3); p = 0.034) and 8.4 cm

Thalidomide: an effective anabolic agent in gastrointestinal cancer cachexia: authors’ reply

“…We agree with Wilkes and Freeman, which the study by Gordon et al 4 suggests, that in this context thalidomide has promising features.…”

“…The study by Gordon et al 4 demonstrates a potential benefit of thalidomide in a small group (N ¼ 17 at 4 weeks and N ¼ 12 at 8 weeks) of patients with end-stage pancreatic cancer on preservation of body weight and lean body mass, but no clear benefit with regard to quality of life was observed. 4 The potential mechanism by which thalidomide may work includes: inhibition of angiogenesis (anticancer effect), decrease in adhesion molecules, inhibition of cyclo-oxygenase 2, modulation of NFjB action and inhibition of proinflammatory mediators, especially tumour necrosis factor (TNF)-a.…”

“…4 The potential mechanism by which thalidomide may work includes: inhibition of angiogenesis (anticancer effect), decrease in adhesion molecules, inhibition of cyclo-oxygenase 2, modulation of NFjB action and inhibition of proinflammatory mediators, especially tumour necrosis factor (TNF)-a. 5 In this context it has to be mentioned that the inflammatory and neurohumoral response with the consecutive catabolic metabolism in stress situationslike cancer or infections is part of a physiological response to maintain lifesaving functions.…”

The Role of Thalidomide and Placebo for the Treatment of Cancer-Related Anorexia-Cachexia Symptoms: Results of a Double-Blind Placebo-Controlled Randomized Study

“…However compared with prior studies, our sample size was smaller, we had a high rate of the attrition, and noncompliance rates were higher. 7,14 We found that there was no significant difference in the toxicity related to the treatment with thalidomide as compared with placebo (Table 4). These results were similar to those of prior studies by our team and of studies by others on the safety of low-dose thalidomide.…”

“…These results were similar to those of prior studies by our team and of studies by others on the safety of low-dose thalidomide. 7,8,[13][14][15] Further studies are needed on the use of thalidomide for ACS based on preliminary safety and efficacy data from prior studies. It is possible that the drug may be of particular utility in the developing world due to its low cost and easy access.…”