Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin.
BACKGROUND
Because of the predictability of significant emesis after its use, cisplatin serves as the standard emetic stimulus for trials of antiemetic drugs. To define better the incidence, severity, and pattern of emesis that follows cisplatin, facilitate the testing of new agents, and obviate the need for further placebo-controlled trials for this indication, individual patient data were compiled from completed studies with placebo antiemetics and cisplatin.


METHODS
The time and number of emetic episodes during the 24 hours after cisplatin were obtained for 48 patients given a placebo antiemetic. Each was treated as part of a randomized, double-blind trial reported between 1981 and 1990. Emesis after antiemetic "rescue" therapy was also assessed.


RESULTS
Emesis occurred in 47 of 48 patients (98% observed rate, 95% confidence interval, 89-99%). The median number of emetic episodes during the 24 hours after cisplatin was 6. Emesis continued after rescue in 77% of patients.


CONCLUSIONS
Cisplatin caused severe emesis that persisted despite rescue in placebo-treated patients. Using the data presented, any therapy preventing acute emesis in 8 or more of the 48 individuals receiving cisplatin > 50 mg/m2 was an active antiemetic (P = 0.05). The four trials discussed here documented the antiemetic effectiveness of granisetron, metoclopramide, and ondansetron. The placebo-treated patients studied can serve as a control group for testing new therapies. Because of the certainty of severe emesis after cisplatin, and the availability both of these data and several proven drugs for this condition, prospective comparisons of antiemetics should employ active control medications.
Kris
M G
MG
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell Medical College, New York, New York, USA.
Cubeddu
L X
LX
Gralla
R J
RJ
Cupissol
D
D
Tyson
L B
LB
Venkatraman
E
E
Homesley
H D
HD
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D017829:Granisetron / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use; D008875:Middle Aged; D017294:Ondansetron / Q000627:therapeutic use; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D002945:Cisplatin; D017829:Granisetron; D008787:Metoclopramide; D017294:Ondansetron; D010919:Placebos