Rolapitant for the prevention of delayed nausea and vomiting over initial and repeat courses of emetogenic chemotherapy

ABSTRACT

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. Although sustained antiemetic control across repeated chemotherapy cycles is important for cancer treatment continuation, few studies have investigated the efficacy of antiemetic prophylaxis over multiple chemotherapy cycles.

Areas covered: Here we discuss the use of antiemetic hydroxytryptamine type 3 (5-HT₃) receptor and neurokinin (NK)-1 receptor antagonists for prevention of CINV, limiting our review to clinical trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1 receptor antagonist rolapitant. 5-HT₃ receptor antagonists may be effective in controlling CINV over repeated chemotherapy cycles, but evidence comes primarily from noncomparative studies. NK-1 receptor antagonists provide increased protection against CINV but differences in endpoint selection and methods of analysis preclude meaningful comparisons between agents. Rolapitant shows sustained control of emesis and nausea over multiple cycles of chemotherapy, and compared to other NK-1 receptor antagonists, has a longer half-life and reduced potential for cytochrome P450 3A4-mediated drug-drug interactions.

Expert commentary: Trial design should be a key consideration in future studies of CINV therapies, including analytical methods utilized, choice of endpoints, and methods for accounting for nonresponders and patient attrition over multiple cycles of chemotherapy.

KEYWORDS:

• Antiemetics
• chemotherapy-induced nausea and vomiting
• highly emetogenic chemotherapy
• moderately emetogenic chemotherapy
• multiple cycles
• neurokinin-1 receptor antagonists
• rolapitant

Information resources

Navari and Aapro have recently published a comprehensive and up-to-date review of CINV [1]. Evidence-based international guidelines for prevention of CINV [4–6] give clear guidance on use of antiemetics in patients receiving HEC and MEC.

Declaration of interest

BL Rapoport received honoraria and expenses from Tesaro, Merck and Co and Herron and is on advisory boards for Tesaro, Merck and Co and Herron and has received research funding from Merck and Co and Tesaro. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript and performed by Jeremy Kennard PhD of Ashfield Healthcare Communications who provided medical writing support and Paula Stuckart of Ashfield Healthcare Communications who provided medical editorial support and funded by Tesaro.

Additional information

Funding

This paper was funded by Tesaro.