Comparison of the efficacy of tropisetron versus a metoclopramide cocktail based on the intensity of cisplatin-induced emesis.
Cisplatin-induced emesis is one of the most feared side effects in cancer treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute emesis. Investigations to test the efficacy of new antiemetics are mandatory. We compared the efficacy, toxicity, and patients' preference for tropisetron, a new 5-hydroxytryptamine3 (HT3) receptor antagonist, with those of a combination of high-dose metoclopramide, dexamethasone, diphenhydramine, and lorazepam (metoclopramide cocktail) in a randomized crossover study for the control of nausea and vomiting during cisplatin-containing chemotherapy. A total of 62 chemotherapy-naive women were included and followed over 3 consecutive courses. Detailed analysis comparing the incidence of acute emesis for each 4 h period following cisplatin infusion was also performed. Complete protection from acute emesis was obtained in 48% of patients receiving tropisetron and 29% of patients receiving the metoclopramide cocktail over the first two courses of chemotherapy (P = 0.029). When the frequency of acute emesis in all patients was compared on a daily basis, no significant difference was found. When emesis frequency was compared over each 4 h period following infusion of cisplatin, tropisetron was superior to the metoclopramide cocktail during the first, the second, and the first and second periods (P = 0.0001, P = 0.01 and P = 0.0006, respectively). This superiority reversed after 12 h but did not reach statistical significance (P = 0.112). Tropisetron was more effective in controlling acute nausea, but metoclopramide provided better control of delayed emesis. A drop in efficacy over successive courses was observed in patients receiving metoclopramide first but was not seen in tropisetron-first patients. A tendency for tropisetron preference was observed. Tropisetron is more effective than the metoclopramide cocktail in the control of chemotherapy-induced vomiting within 8 h of the implementation of cisplatin and in the control of nausea on the 1st day. To improve the control of chemotherapy-induced emesis, further investigations on the additional tropisetron dosing at 8 h after cisplatin infusion or the combination use of tropisetron and other antiemetics by a continuous 4 h period of observation and comparison are mandatory.
Chang
T C
TC
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Hsieh
F
F
Lai
C H
CH
Tseng
C J
CJ
Cheng
H H
HH
Li
C L
CL
Michael
B J
BJ
Soong
Y K
YK
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008787:Metoclopramide / Q000627:therapeutic use*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D012720:Severity of Illness Index; D013997:Time Factors; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D000077526:Tropisetron; D008787:Metoclopramide; D002945:Cisplatin