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 con trol of cisplatin induced emesis. Nevertheless, a significant proporti on of patients still experience emesis despite the use of these antiem etics. The aim of this study was to evaluate if cisplatin treated pati ents 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-H IAA), 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 comple tely protected from vomiting. Three groups of patients without chemoth erapy served as control. The first group did not receive any medicatio n. 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 crea tinine). Neither ondansetron nor metoclopramide given without chemothe rapy induced significant changes in 5-HIAA excretion patterns. 23 cour ses (55%) were associated with acute cisplatin-induced emesis. The med ian interval from the start of the cisplatin infusion to the peak 5-HI AA excretion was shorter in patients with acute emesis, but the cumula tive amount of urinary 5-HIAA did not differ between patients with or without emesis. Patients who are efficiently protected from vomiting a s 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 experience d cisplatin-induced delayed emesis. Further studies are warranted to i dentify the pathomechanisms responsible for delayed emesis as well as that proportion of acute emesis which is refractory to 5-HT3 antagonis m.