Antiemetic - casopitant

Nausea and vomiting are very common side-effects of cancer treatment, and are a particular problem with various forms of chemotherapy. One of the mechanisms responsible involves a central pathway that is activated by substance P and mediated by tachykinin NK1 receptors in the brain stem, which control the vomiting reflex.

The drug aprepitant acts by antagonising the NK1 receptors, and is generally administered in combination with drugs such as ondansetron, which antagonise the peripheral 5HT-3 receptors that are also implicated in nausea and vomiting. Another NK1 receptor antagonist, casopitant mesilate has been developed by GlaxoSmithKline, and has been submitted for approval.

Several studies have been carried out, including a matched pair of Phase II trials in two groups of patients being given highly and moderately emetogenic chemotherapy respectively.^1,2 In the multicentre randomised, double blind, placebo and active controlled parallel group trials, subjects were given doses of between 50 and 150mg of the drug or placebo for three days or 150mg on the first day alone, plus ondansetron and dexamethasone. Patients in both achieved a complete response during the first 120 hours after the chemotherapy drugs were administered. The single dose appeared to be just as effective as multiple doses.

A similar pair of Phase III trials were carried out. Those on highly emetogenic chemotherapy were given ondansetron and dexamethosone plus either 150mg casopitant on the first day orally, or 90mg intravenously on the first day followed by 50mg orally on days two and three.³ A similar regime was given to those on moderately emetogenic chemotherapy, except the oral group were also given the subsequent smaller oral doses.⁴ Either way, in the HEC group the complete response rate was 14-20% better in those given casopitant, and 14-15% in the MEC group. The effect was maintained across multiple cycles of chemotherapy.