The purpose of this study was to compare the
antiemetic efficacy of three
5-HT3 antagonists (
granisetron,
ondansetron,
tropisetron) plus
dexamethasone for the prevention of acute
emesis induced by high-dose
cisplatin chemotherapy. This was a randomized, open label, crossover study. Recruited into the study were 94
chemotherapy-naive patients of whom five were excluded because
chemotherapy was not given, noncisplatin regimen was used instead, or presence of
anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and
neck cancers. The
antiemetic regimens consisted of 1)
granisetron 3 mg i.v. and
dexamethasone 20 mg i.v. on day 1 (
GRADEX); 2)
tropisetron 5 mg i.v. and
dexamethasone 20 mg i.v. on day 1 (TRODEX); and 3)
ondansetron 8 mg i.v. and
dexamethasone 20 mg i.v. to be followed by
ondansetron 8 mg p.o. x 2 on day 1 (ONDEX). Patients were randomized to receive one of the three regimens in the first cycle, and treatment was crossed over to the other two regimens in subsequent cycles.
Antiemetic efficacy was assessed using self-report diaries recording the number of
vomiting episodes as well as duration and severity of
nausea within the first 24 hours. Complete response was defined as no
vomiting with or without mild
nausea, and major response was defined as one
vomiting episode and/or moderate to severe
nausea. Major efficacy refers to either complete or major response. A total of 219 cycles was given to 89 patients: 16 received one cycle only, 16 received two cycles, and 57 received three cycles. No carryover effects were observed between cycles. Using pooled data from all cycles, the complete response rates to
GRADEX, TRODEX, and ONDEX were 81%, 68%, and 71%, respectively (p = 0.11); the corresponding major efficacy rates were 91%, 93%, and 86%, respectively (p = 0.36). When only the first cycle was considered, the complete response rates to
GRADEX, TRODEX, and ONDEX were 81%, 75%, and 74%, respectively (p = 0.58); the corresponding major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). Analysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, and there were no significant differences between different regimens in terms of complete response or major efficacy. The only exception was
GRADEX versus TRODEX, in which 15.5% of patient achieved complete response with
GRADEX as compared with 1.7% with TRODEX (p = 0.025). The majority of patients (53%) did not report any preference, whereas 14% preferred
GRADEX, 15% preferred TRODEX, and 18% preferred ONDEX. The three
5-HT3 antagonists, when used in combination with
steroids, had similar major efficacy for prophylaxis against
cisplatin-induced acute
emesis. Although
GRADEX was superior to TRODEX in terms of complete response, this may not be of clinical significance. The choice of
antiemetic regimens should therefore depend on patient preference and drug cost.