Adding fosaprepitant to palonosetron and dexamethasone reduced the risk for nausea and emesis in patients undergoing radiotherapy and concomitant weekly cisplatin, a study published in the journal The Lancet Oncology has shown.1
Although neurokinin-1 (NK-1) receptor antagonists such as aprepitant and its intravenous counterpart, fosaprepitant, are widely used for the prevention of chemotherapy-induced nausea and vomiting (CINV), their role in the prevention of radiation-induced nausea and vomiting remains unclear.
Therefore, researchers sought to evaluate the efficacy and safety of fosaprepitant in combination with palonosetron and dexamethasone in the prevention of nausea and vomiting during 5 weeks of fractionated radiotherapy and concurrent cisplatin.
For the international, double-blind, placebo-controlled, phase 3 trial, researchers enrolled 234 treatment-naïve women with cervical cancer undergoing fractionated radiotherapy plus weekly cisplatin 40 mg/m2 IV for 5 weeks.
Participants were randomly assigned 1:1 to receive either fosaprepitant 150 mg IV or placebo in combination with palonosetron 0.25 mg IV and oral dexamethasone 16 mg prior to cisplatin administration. Patients also received oral dexamethasone 8 mg twice daily on day 2, 4 mg twice daily on day 3, and 4 mg once daily on day 4.
Results showed that 65.7% (95% CI: 42.2-89.2) of patients in the fosaprepitant arm sustained no emesis at 5 weeks compared with 48.7% (95% CI: 25.2-72.2) in the placebo group (HR, 0.58; 95% CI: 0.39-0.87; P=.008).
In terms of safety, the most frequently reported grade 3 adverse event was diarrhea, which occurred in 9% of fosaprepitant-treated patients and 5% of those receiving placebo. One incidence of grade 4 neutropenia occurred in the fosaprepitant arm.
The findings suggest that further investigations of fosaprepitant in combination with dexamethasone and a 5HT-3 receptor antagonist in other radiotherapy settings are warranted.
1. Ruhlmann CH, Christensen TB, Dohn LH, et al. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial [published online ahead of print March 4, 2016]. Lancet Oncol. doi:10.1016/S1470-2045(15)00615-4.