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 (5HT₃) can ameliorate anorexia in this animal model. Imbalanced plasma amino acid levels also have been documented in both animal models and human patients with cancer cachexia. Therefore a trial of the 5HT₃ receptor antagonist, ondansetron, was undertaken in the treatment of patients with cancer cachexia. METHODS. Patients with metastatic cancer who were not undergoing chemotherapy or radiotherapy and who had lost >5% of their body weight were eligible. Baseline physical examination; weight; anthropometric studies; levels of retinol binding protein, albumin, and prealbumin; and skin testing for anergy were obtained. The ability to enjoy food was assessed utilizing a seven-point hedonic category scale for specific foods. Therapy was comprised of oral ondansetron, 8 mg twice a day. RESULTS. Twenty-seven patients were enrolled; all were evaluable for toxicity and 20 patients were evaluable for response. Toxicity of ondansetron was minimal. Patients demonstrated significant weight loss prior to disease entry (mean baseline weight of 76.9 kg vs. 72.1 kg; P < 0.000002). Patients continued 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 circumference 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 enjoy food, the blockade of 5HT₃ receptors failed to prevent weight loss in patients with cancer cachexia or alter laboratory parameters of protein nutrition.