CISPLATIN-INDUCED ALTERATIONS OF SEROTONIN METABOLISM IN PATIENTS WITH OR WITHOUT EMESIS FOLLOWING CHEMOTHERAPY

Serotonin (5-HT)(3) receptor antagonists are very effective in the control of cisplatin induced emesis. Nevertheless, a significant proportion of patients still experience emesis despite the use of these antiemetics. The aim of this study was to evaluate if cisplatin treated patients who vomit differ from patients who are completely protected from emesis with respect to measurable alterations of serotonin metabolism. We measured the urinary excretion of 5-hydroxyindole-acetic-acid (5-HIAA), the main metabolite of serotonin, in 24 patients with 42 courses of cisplatin containing chemotherapies. Patterns of 5-HIAA excretion were compared between patients with emesis and patients who are completely protected from vomiting. Three groups of patients without chemotherapy served as control. The first group did not receive any medication. The second and third group were given a single dose of ondansetron or metoclopramide. The median 5-HIAA/creatinine ratios in the control group ranged from 3.8 to 6.9 with a median of 6.2 (mu g 5-HIAA/mg creatinine). Neither ondansetron nor metoclopramide given without chemotherapy induced significant changes in 5-HIAA excretion patterns. 23 courses (55%) were associated with acute cisplatin-induced emesis. The median interval from the start of the cisplatin infusion to the peak 5-HIAA excretion was shorter in patients with acute emesis, but the cumulative amount of urinary 5-HIAA did not differ between patients with or without emesis. Patients who are efficiently protected from vomiting as well as patients who experience emesis show a comparable increase in urinary 5-HIAA following cisplatin therapy. The present study failed to show elevated 5-HIAA excretion levels occurring later than 24 hours following cisplatin administration. Nevertheless, patients experienced cisplatin-induced delayed emesis. Further studies are warranted to identify the pathomechanisms responsible for delayed emesis as well as that proportion of acute emesis which is refractory to 5-HT3 antagonism.