5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of chemotherapy-induced emesis

Abstract

Summary This study evaluated the relationship between prechemotherapy cortisol and 5-hydroxyindoleacetic acid (5-HIAA) excretion and chemotherapy-induced emesis. The urinary excretion of cortisol and the serotonin metabolite 5-HIAA in the night before chemotherapy administration were measured in 28 and 49 female patients receiving > 300 mg m-2 carboplatin. Vomiting and nausea were documented over a 3 day observation period. Lower basal cortisol excretion was significantly correlated with vomiting with or without nausea occurring within the observation period. 5-HIAA showed only a weak correlation with emesis on days 1-3, but low 5-HIAA excretion was correlated with a higher proportion of patients vomiting on days 2 -3 following chemotherapy. Low basal cortisol excretion might be useful as a predictor for chemotherapy-induced emesis and therefore should be evaluated prospectively in future studies.Keywords: cortisol; 5-hydroxyindoleacetic acid (5-HIAA); vomiting; emesis; chemotherapy; carboplatin Vomiting and nausea are distressing side-effects of cytostatic drug treatment (Coates et al., 1983) and efficient anti-emetic prophylaxis is mandatory for the maintenance of life quality and the patients' compliance with chemotherapy. Cisplatin, carboplatin and cyclophosphamide are widely used cytostatics which possess a remarkable emetogenic potential. Treatment without anti-emetic prophylaxis leads to emesis in the majority of patients (Gralla et al., 1981;Martin et al., 1990;Beck et al., 1993). The combination of 5-hydroxytryptamine-3-receptor (5-HT3) antagonists with corticosteroids represents the most effective anti-emetic treatment in platinum-based and cyclophosphamide-based chemotherapy (Roila et al., 1991;Italian Group for Antiemetic Research, 1995). These clinical experiences as well as experimental data (Cubeddu et al., 1990;Schworer et al., 1991;Miner et al., 1987;Fredrickson et al., 1992) indicate a role for serotonin and corticosteroid metabolism in the pathophysiology of emesis. The mechanism of anti-emetic action of the 5-HT3 antagonists mainly reflects their capability of blocking 5-HT3 receptors which are believed to play a crucial role in the afferent part of the emetic reflex. The mechanisms of the antiemetic action of corticosteroids are still unclear: increased 5-HT turnover or reduced 5-HT synthesis (Young, 1981;Munck et al., 1984) or an affection of the permeability of the blood -brain barrier (Livera et al., 1985) The aim of this study was to evaluate the relation between pre-chemotherapeutic 5-HIAA and cortisol excretion levels and chemotherapy-induced emesis in carboplatin-treated female patients. This analysis should add information about the role of 5-HT and cortisol metabolism in the pathophysiology of chemotherapy-induced emesis. Methods PatientsA total of 54 patients who received a carboplatin-based chemotherapy regimen gave informed consent and were enrolled into the study. Five patients were excluded because they had failed to complete the 12 h urine collection. Data from 49 patients we...

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