Background: Nausea and vomiting are among the most feared side effects of chemotherapy
and can prevent cancer patients from completing their treatment regimens. Rolapitant is a highly
selective neurokinin-1 (NK-1) receptor antagonist with very good oral activity, central nervous system
penetration and a long (180-hour) plasma half-life. Unlike other available NK-1 receptor antagonists,
rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4.
Methods: Findings from recent phase II and III clinical trials of rolapitant in patients receiving
highly or moderately emetogenic chemotherapy are reviewed and discussed.
Results: The addition of a single-dose of rolapitant to combination 5-hydroxytryptamine type 3 receptor
antagonist and dexamethasone regimens provided increased protection against chemotherapyinduced
nausea and vomiting, a benefit that encompassed the entire at-risk period investigated (0-120
hours after initiation of chemotherapy) in patients receiving highly or moderately emetogenic chemotherapy.
Rolapitant was well tolerated by patients in these trials, with the overall frequency of treatment-
related adverse events similar in patients receiving rolapitant (7.0%) and active placebo (6.3%).
Conclusion: Rolapitant’s favorable toxicity profile and lack of CYP3A4-related drug-drug interactions
indicate that it would be a suitable treatment for older patients or those with multiple comorbidities,
who are likely to be receiving a number of concomitant medications. Future studies should focus
on the role of rolapitant in the control of chemotherapy-induced nausea and vomiting in patients
receiving multiple-day chemotherapy, specific chemotherapy agents or high-dose chemotherapy and
stem cell support.