Comparison of the 5-Hydroxytryptamine₃(Serotonin) Antagonist Ondansetron (Gr 38032F) with High-Dose Metoclopramide in the Control of Cisplatin-Induced Emesis

Abstract

To compare ondansetron (GR 38032F), a 5-hydroxytryptamine3-receptor antagonist, with metoclopramide in the prophylaxis of acute cisplatin-induced emesis, we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin (80 to 100 mg per square meter of body-surface area) for treatment of cancer. None had received chemotherapy before this trial. Among the 76 patients who satisfactorily completed both parts of the study, complete or nearly complete control of emesis (i.e., no episodes of emesis occurred, or only one or two) was achieved in 57 of 76 treatments (75 percent) with ondansetron and in 32 of 76 treatments (42 percent) with metoclopramide (P less than 0.001). Ondansetron was also more effective in controlling acute nausea, as assessed with a visual-analogue scale (P = 0.019) or a graded scale (P = 0.024). There was a significant preference among patients for ondansetron (55 vs. 26 percent; P = 0.006). Dystonic reactions were observed during three treatments with metoclopramide; both agents were otherwise well tolerated. We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting, and that this suggests that serotonin is an important mediator of this side effect.

Chemotherapy-Induced Nausea and Vomiting: The Importance of Acute Antiemetic Control

“…Comparative trials with high-dose metoclopramide have demonstrated that dolasetron, ondansetron, and granisetron are more effective in preventing acute emesis, are better tolerated, and are preferred by more patients [1,19,[48][49][50]. 5-HT 3 -receptor antagonists have become the agents of choice in preventing acute CINV following both moderately and highly emetogenic chemotherapy [11,51].…”

Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles

“…The prevention and treatment of these symptoms was greatly improved with the development of selective 5HT3-receptor antagonists, which control nausea and vomiting in more than 70% of cisplatin-treated patients in the first cycle of chemotherapy (Marty et al, 1990;de Mulder et al, 1990;Hainsworth et al, 1991). Anti-emetic protection against both acute and delayed emesis is improved further by the combined use of a 5HT3 antagonist plus dexamethasone (Roila et al, 1991;Smith et al, 1991;Ahn et al, 1994;Hesketh et al, 1994; Italian Group for Antiemetic Research, 1995).…”

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours

“…Until recently, even with the use of the most active antiemetic combination regimen (metoclopramide with lorazepam and dexamethasone), a considerable proportion of patients suffered from nausea and vomiting whereas the new 5HT3-antagonists are now found to be more effective in preventing acute nausea and vomiting induced by cisplatin (Cubbedu et al, 1990;Marty et al, 1990;Smith et al, 1990; de Mulder et al, 1990). …”