Cisplatin-induced emesis: Systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

Abstract

Purpose: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT3 receptor antagonists to assess its translational validity. Methods: A systematic review identified available evidence and was used to perform meta-analyses. Results: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg-1 dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg-1, which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT3 receptor antagonists reduced cisplatin (5 mg kg-1) emesis by 68% (45-91%) during the acute phase (day 1) and by 67% (48-86%) and 53% (38-68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. Conclusion: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT3 receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret. © 2010 The Author(s).