Pancreatic Cancer Patients With Cachexia May Benefit From Thalidomide

Laurie Barclay, MD

March 08, 2005

March 8, 2005 — Pancreatic cancer patients with cachexia may benefit from thalidomide, according to the results of a randomized study published in the April issue of Gut.

"Proinflammatory cytokines, especially tumour necrosis factor α (TNF-α), play a prominent role in the pathogenesis of cancer cachexia," write J. N. Gordon, from Queen Alexandra Hospital in Portsmouth, U.K., and colleagues. "Thalidomide, which is an inhibitor of TNF-α synthesis, may represent a novel and rational approach to the treatment of cancer cachexia."

In this single-center, double-blind trial, 50 patients with advanced pancreatic cancer who had lost at least 10% of their body weight were randomized to receive thalidomide, 200 mg daily, or placebo for 24 weeks. The main outcome measure was change in weight and nutritional status.

Of 33 patients (17 receiving thalidomide and 16 control subjects) evaluated at four weeks, 20 patients (12 thalidomide, eight control) were also evaluated at eight weeks. At four weeks, patients who received thalidomide had average gains of 0.37 kg in weight and 1.0 cm 3 in arm muscle mass (AMA), whereas the placebo group had an average loss of 2.21 kg (absolute difference, 22.59 kg; 95% confidence interval [CI], 24.3 - 20.8; P = .005) and 4.46 cm 3 (absolute difference, 25.6 cm 3 (95% CI, 28.9 - 22.2; P = .002).

At eight weeks, losses were 0.06 kg in weight and 0.5 cm 3 in AMA in the thalidomide group compared with a loss of 3.62 kg (absolute difference, 23.57 kg; 95% CI, 26.8 - 20.3; P = .034) and 8.4 cm 3 (absolute difference, 27.9 cm 3; 95% CI, 214.0 - 21.8; P = .014) in the placebo group. Improvement in physical functioning was positively correlated with weight gain (r = 0.56; P = .001).

Study limitations include high attrition rate; patients in the placebo group were 4 kg lighter on average than those in the treatment group; indirect estimate of lean body mass; lack of power to detect small changes in quality of life; and lack of power to determine survival benefit.

"Thalidomide was well tolerated and effective at attenuating loss of weight and lean body mass in patients with cachexia due to advanced pancreatic cancer," the authors write. "It remains to be seen whether these results can be generalized to all cancers and whether attenuation of weight loss leads to prolonged survival. In the future, combination of thalidomide with nutritional supplements and pharmacological agents may ultimately lead to a better clinical outcome."

The authors report no financial conflicts of interest.

In an accompanying editorial, M. Stroud, from Southampton General Hospital, U.K., discusses the mechanisms underlying cancer cachexia and its amelioration by thalidomide.

"Improved understanding of the triggers and responses underlying cancer cachexia offers new targets for potential therapeutic intervention," Dr. Stroud writes. "Clearly, larger multicentre

studies of thalidomide in pancreatic and other gastrointestinal cancers are required and should be undertaken as soon as possible."

Dr. Stroud reports no financial conflicts of interest.

Gut. 2005;54:447-448, 540-545

Reviewed by Gary D. Vogin, MD

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