On the mechanism of radiation-induced emesis: the role of serotonin.

Abstract

The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation; the effects of specific antiemetics especially ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the relationship between radiation-induced emesis and serotonin (5-hydroxytryptamine) through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Forty-one patients received 53 hemibody treatments of 5-8 Gy following intravenous hydration. The patients were divided into three groups according to prehemibody irradiation treatment: Group A: no pretreatment antiemetics, 30 patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone, prochlorperazine), ten patients; and Group C: ondansetron, 13 patients. The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA (ng/ug creatinine). The incidence of radiation-induced emesis was 82% (14/17) following upper/mid hemibody irradiation and 15% (2/11) following lower hemibody irradiation in Group A; 50% (3/6) and 25% (1/4) following upper/mid and lower hemibody irradiation respectively, in Group B; and 0% (0/13) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different (p < 0.001) between the patients of Group A and C who received upper/mid hemibody irradiation. The percent change in 5-HIAA excretion following upper/mid hemibody irradiation were greatest in Group A and smallest in Group C (p < 0.002). The degree of change following lower hemibody irradiation (15% incidence of emesis) in Group A was lower than upper/mid hemibody irradiation of the same group. The higher incidence of radiation-induced emesis following upper and mid hemibody irradiation in antiemetic naive patients compared to the incidence following lower hemibody irradiation suggests that the critical organ responsible for radiation sickness is in the abdomen. The control of emesis by ondansetron, a 5-HT3 receptor antagonist, attests to the efficacy of ondansetron in radiation-induced emesis and suggests a role for serotonin in mediating radiation-induced emesis. Finally, the parallel changes in 5-HIAA and the incidence of emesis provides additional evidence for a more direct role for serotonin in radiation-induced emesis.