Thalidomide for cancer cachexia – pro

The cancer cachexia syndrome is common. Significant weight loss occurs in approximately 50% of oncology patients, with even higher values in those with gastrointestinal tumours.1 In pancreatic cancer, approximately 80% of patients will become severely malnourished. The development of cachexia is not only distressing for patients and their families, it is also associated with a much worse clinical outcome. Malnourished patients undergoing surgery for cancer have morbidity and mortality rates of three to four times those of their better nourished counterparts,2 and wasted weakened patients also tolerate chemoradiation poorly. Ultimately, malnutrition itself can be considered to be the final cause of death in approximately 30% of cancer patients. It occurs once patients have lost about one third of their premorbid body weight.

Pancreatic cancer patients with cachexia may benefit from thalidomide, according to the results of a randomized study published in the April, 2008 issue of Gut.

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 cm3 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 cm3 (absolute difference, 25.6 cm3 (95% CI, 28.9 – 22.2; P = .002).

At eight weeks, losses were 0.06 kg in weight and 0.5 cm3 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 cm3 (absolute difference, 27.9 cm3; 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).

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

Stroud, M Thalidomide and cancer cachexia: old problem, new hope?
Gut 2005 54: 447-448
Gut. 2005;54:447-448, 540-545

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