Despite recent advances in control of acute
emesis, delayed
nausea and
vomiting following
cisplatin-based
chemotherapy remain a significant cause of treatment-related morbidity.
Ondansetron, a selective 5HT3 receptor antagonist, is effective in preventing acute
emesis in the initial 24-h period following high-dose
cisplatin. The efficacy and safety of
ondansetron in preventing the delayed
emesis syndrome during days 2-5 after
cisplatin (> or = 100 mg/m2) were evaluated in a double-blind, placebo-controlled multicentre trial. 50 patients having two or fewer
emetic episodes during the first 24 h were randomised to receive
ondansetron (16 mg) or placebo orally three times daily beginning 24 h after
cisplatin. Rates of complete control of
emesis were higher in
ondansetron-treated patients during each study day, 59-78%, compared with 39-50% in placebo-treated patients, but the differences were statistically superior only on the third study day (P = 0.009). 40% of patients in the
ondansetron treatment arm and 33% treated with placebo had complete control of
emesis during the entire 4-day study period (P = 0.648). Withdrawal from study due to
nausea and
vomiting occurred in 13% of
ondansetron-treated patients compared with 33% in the placebo arm (P = 0.102). Control of
nausea was better with
ondansetron, but differences were not statistically significant. Adverse effects of oral
ondansetron given in this dose schedule were minimal. These data suggest that the delayed
emesis syndrome may be partially mediated through the 5HT3 receptor, but that a
serotonin antagonist alone provides inadequate control. Further investigation of
ondansetron-based
therapy in this clinical setting is warranted.