Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome

BACKGROUND. Imbalanced amino acid diets in animals rapidly produce anorexia and weight loss. Blockade of type 3 serotonergic receptors (5HT(3)) can am eliorate anorexia in this animal model. Imbalanced plasma amino acid levels also have been documented in both animal models and human patients with ca ncer cachexia. Therefore a trial of the 5HT(3) receptor antagonist, ondanse tron, was undertaken in the treatment of patients with cancer cachexia. METHODS. Patients with metastatic cancer who were not undergoing chemothera py or radiotherapy and who had lost >5% of their body weight were eligible. Baseline physical examination; weight; anthropometric studies; levels of r etinol binding protein, albumin, and prealbumin; and skin testing for anerg y were obtained. The ability to enjoy food was assessed utilizing a seven-p oint hedonic category scale for specific foods. Therapy was comprised of or al ondansetron, 8 mg twice a day. RESULTS. Twenty-seven patients were enrolled; all were evaluable for toxici ty and 20 patients were evaluable for response. Toxicity of ondansetron was minimal. Patients demonstrated significant weight loss prior to disease en try (mean baseline weight of 76.9 kg vs. 72.1 kg; P < 0.000002). Patients c ontinued to lose weight on study (Week 0: 72.5 kg vs. Week 4: 71.4 kg; P = 0.027); in addition, there was significant deterioration of midarm circumfe rence and hand grip strength, all of which indicated worsening nutritional status. However, a significant improvement in food enjoyment was noted (P = 0.04). CONCLUSIONS. Although it apparently improved the ability of patients to enj oy food, the blockade of 5HT(3) receptors failed to prevent weight loss in patients with cancer cachexia or alter laboratory parameters of protein nut rition. Cancer 1999;86:684-8. (C) 1999 American Cancer Society.