Comparative efficacy of three 5-HT3 antagonists (granisetron, ondansetron,and tropisetron) plus dexamethasone for the prevention of cisplatin-induced acute emesis - A randomized crossover study

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 chemothe rapy. This was a randomized, open label, crossover study. Recruited into th e study were 94 chemotherapy-naive patients of whom five were excluded beca use chemotherapy was not given, noncisplatin regimen was used instead, or p resence of anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and neck cancers. The an tiemetic regimens consisted of 1) granisetron 3 mg i.v. and dexamethasone 2 0 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 2 0 mg i.v. to be followed by ondansetron 8 mg p.o. X 2 on day 1 (ONDEX). Pat ients were randomized to receive one of the three regimens in the first cyc le, and treatment was crossed over to the other two regimens in subsequent cycles. Antiemetic efficacy was assessed using self-report diaries recordin g the number of vomiting episodes as well as duration and severity of nause a within the first 24 hours. Complete response was defined as no vomiting w ith or without mild nausea, and major response was defined as one vomiting episode and/or moderate to severe nausea. Major efficacy refers to either c omplete 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 c ycles. 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 correspending major ef ficacy 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 correspondi ng major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). An alysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, a nd there were no significant differences between different regimens in term s of complete response or major efficacy. The only exception was GRADEX ver sus TRODEX, in which 15.5% of patient achieved complete response with GRADE X 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% prefe rred TRODEX, and 18% preferred ONDEX. The three 5-HT3 antagonists, when use d in combination with steroids, had similar major efficacy for prophylaxis against cisplatin-induced acute emesis. Although GRADEX was superior to TRO DEX in terms of complete response, this may not be of clinical significance . The choice of antiemetic regimens should therefore depend on patient pref erence and drug cost.