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

Martin J. Edelman, David R Gandara, Frederick J Meyers, Rie Ishii, Michael O'Mahony, Margaret Uhrich, Ignacio Lauder, Joan Houston, Dorothy W. Gietzen

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)684-688
Number of pages5
JournalCancer
Volume86
Issue number4
DOIs
StatePublished - Aug 15 1999

Fingerprint

Cachexia
Anorexia
Ondansetron
Neoplasms
Weight Loss
Food
Therapeutics
Hand Strength
Weights and Measures
Animal Models
Amino Acids
Retinol-Binding Proteins
Prealbumin
Pleasure
Nutritional Status
Physical Examination
Albumins
Radiotherapy
Body Weight
Diet

Keywords

  • Cancer cachexia
  • Ondansetron
  • Serotonergic blockade
  • Type 3 serotonin receptors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome. / Edelman, Martin J.; Gandara, David R; Meyers, Frederick J; Ishii, Rie; O'Mahony, Michael; Uhrich, Margaret; Lauder, Ignacio; Houston, Joan; Gietzen, Dorothy W.

In: Cancer, Vol. 86, No. 4, 15.08.1999, p. 684-688.

Research output: Contribution to journalArticle

Edelman, Martin J. ; Gandara, David R ; Meyers, Frederick J ; Ishii, Rie ; O'Mahony, Michael ; Uhrich, Margaret ; Lauder, Ignacio ; Houston, Joan ; Gietzen, Dorothy W. / Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome. In: Cancer. 1999 ; Vol. 86, No. 4. pp. 684-688.
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T1 - Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome

AU - Edelman, Martin J.

AU - Gandara, David R

AU - Meyers, Frederick J

AU - Ishii, Rie

AU - O'Mahony, Michael

AU - Uhrich, Margaret

AU - Lauder, Ignacio

AU - Houston, Joan

AU - Gietzen, Dorothy W.

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N2 - 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.

AB - 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.

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KW - Ondansetron

KW - Serotonergic blockade

KW - Type 3 serotonin receptors

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