A. Dubois et al., CISPLATIN-INDUCED ALTERATIONS OF SEROTONIN METABOLISM IN PATIENTS WITH OR WITHOUT EMESIS FOLLOWING CHEMOTHERAPY, Oncology Reports, 2(5), 1995, pp. 839-842
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.