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

Abstract

Background: Proinflammatory cytokines, especially tumour necrosis factor alpha (TNF-alpha), play a prominent role in the pathogenesis of cancer cachexia. Thalidomide, which is an inhibitor of TNF-alpha 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 -2.59 kg (95% confidence interval (CI) -4.3 to -0.8); p = 0.005) and 4.46 cm(3) (absolute difference -5.6 cm(3) (95% CI -8.9 to -2.2); 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 -3.57 kg (95% CI -6.8 to -0.3); p = 0.034) and 8.4 cm(3) (absolute difference -7.9 cm(3) (95% CI -14.0 to -1.8); p = 0.014) in the placebo group. Improvement in physical functioning correlated positively with weight gain (r = 0.56, p = 0.001).

Conclusion: Thalidomide was well tolerated and effective at attenuating loss of weight and lean body mass in patients with cachexia due to advanced pancreatic cancer.

Figure 1

Flow diagram of progress through the trial.

Figure 2

Change in weight in pancreatic cancer patients randomised to either thalidomide (n = 17, week 4; n = 12, week 8) or placebo (n = 16, week 4; n = 8, week 8). Differences between groups: p = 0.005 at four weeks and p = 0.034 at eight weeks.

Figure 3

Change in bone free arm muscle area (AMA) in pancreatic cancer patients randomised to either thalidomide (n = 17, week 4; n = 12, week 8) or placebo (n = 16, week 4; n = 8, week 8). Differences between groups: p = 0.002 at four weeks and 0.014 at eight weeks.

Figure 4

Relationship between change in physical performance status and change in weight at four weeks in patients with pancreatic cancer (n = 34, p = 0.001).

Figure 5

Relationship between change in global health status and change in weight at four weeks in patients with pancreatic cancer (n = 34, p = 0.221).

Figure 6

Kaplan-Meier survival curve for patients with pancreatic cancer treated with thalidomide (n = 23) or placebo (n = 24). Median survival 148 days in thalidomide group versus 110 days in the placebo group (p = 0.45).