CHEMOTHERAPY Rolapitant—A New and Safer Antiemetic Agent Chemotherapy-Induced Nausea and Vomiting (CINV) Is One of the Most Feared Adverse Effects of Chemotherapy

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RESEARCH HIGHLIGHTS Nature Reviews Clinical Oncology 12, 562 (2015); published online 25 August 2015; doi:10.1038/nrclinonc.2015.144

CHEMOTHERAPY Rolapitant—a new and safer antiemetic agent Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared adverse effects of chemotherapy. Now, three trials, all coordinated by Lee Schwartzberg and Bernardo Rapoport, show that rolapitant is a novel, safe and effective agent for the prevention of CINV. CINV is divided into an acute phase (the first 24 h after treatment initiation) and a delayed phase (24–120 h after treatment); serotonin is the main mediator of the acute phase reactions, whereas those

that occur in the delayed phase cbenjasuwan/iStock/Thinkstock are mediated by neurokinin-1 (NK-1) and substance P. Thus, emesis, which addresses an unmet current treatment guidelines clinical need. In addition, patients for the prevention of CINV receiving rolapitant who did not recommend the use of an develop CINV in the acute phase NK-1 receptor antagonist, a were more likely to not develop serotonin receptor antagonist and CINV in the delayed phase. dexamethasone. However, most “Rolapitant’s long half-life offers NK-1 receptor antagonists interact us the opportunity to further with CYP3A4 and, therefore, affect explore dosing options—maybe the pharmacokinetics of drugs it can be given the day before administered concomitantly. chemotherapy if that is more Rolapitant is an NK-1 receptor convenient for the patient,” antagonist with high affinity for says Rapoport. Schwartzberg the human NK-1 receptor that concludes, “patients often believe does not interact with CYP3A4. Its that they are supposed to vomit on half-life is around 180 h and thus chemotherapy, but the reality is we a single dose might be sufficient have very good drugs to prevent to prevent CINV. The aim of three this. Some patients will stop their phase III trials was to assess the treatment because of their CINV safety and efficacy of rolapitant and that’s the last thing we want.” in combination with granisetron Diana Romero (a 5-HT₃ receptor antagonist) and dexamethasone to prevent CINV Original articles Rapoport, B. L. et al. Safety induced by moderately emetic and efficacy of rolapitant for prevention chemotherapy (MEC) and highly of chemotherapy-induced nausea and vomiting after administration of cisplatin- emetic chemotherapy (HEC). based highly emetogenic chemotherapy The MEC agents used were in patients with cancer: two randomised, carboplatin, cyclophosphamide active-controlled, double-blind, phase 3 and irinotecan, among others. trials. Lancet Oncol. doi:10.1016/S1470- The HEC agents used were 2045(15)00035-2 | Schwartzberg, L. S. cisplatin, and anthracycline plus et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea cyclophosphamide combinations. and vomiting after administration of moderately In both the MEC and HEC emetogenic chemotherapy or anthracycline settings, a significantly greater and cyclophosphamide regimens in patients proportion of patients treated with cancer: a randomised, active-controlled, with rolapitant compared with double-blind, phase 3 trial. Lancet Oncol. doi:10.1016/S1470-2045(15)00034-0 placebo had no delayed-phase