Palonosetron with aprepitant plus dexamethasone to prevent chemotherapy-induced nausea and vomiting during gemcitabine/cisplatin in urothelial cancer patients.

Abstract

To evaluate the appearance of chemotherapy-induced nausea and vomiting, and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using first-generation 5-hydroxytryptamine 3-receptor antagonists and dexamethasone during gemcitabine and cisplatin chemotherapy in patients with advanced urothelial cancer. We carried out a multi-institutional study including 122 patients who received gemcitabine and cisplatin for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled chemotherapy-induced nausea and vomiting events were identified through records of nausea and vomiting, additional infusion, rescue medications, and/or records of food intake. First-generation 5-hydroxytryptamine3-receptor antagonists (ondansetron or granisetron) plus dexamethasone were used for 75 patients (cohort1), and palonosetron with dexamethasone plus aprepitant for 47 patients (cohort2). Patients in cohort2 had significantly higher complete response (defined as no emetic episodes and no rescue medication use) rates than those in cohort1 during the overall phase in the first cycle (85.7% vs 65.3%, P=0.012), and all cycles (78.7% vs 50.7%, P=0.0019) of gemcitabine and cisplatin. Patients in cohort2 were more likely to achieve more favorable chemotherapy-induced nausea and vomiting control; that is, a lower grade of nausea, vomiting or anorexia, lower incidence of rescue therapy required, and shorter time to become chemotherapy-induced nausea- and vomiting-free than patients in cohort1. The present results show that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in urothelial cancer patients treated with gemcitabine and cisplatin than first-generation 5-hydroxytryptamine3-receptor antagonists plus dexamethasone.