Recent advances in antiemetics: New formulations of 5HT3-receptor antagonists

Abstract

Purpose: To discuss new therapeutic strategies for chemotherapy-induced nausea and vomiting (CINV) involving 5-hydroxytryptamine type 3 (5HT3)-receptor antagonists (RAs). Summary: CINV remains poorly controlled in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC); nausea and delayed-phase CINV (24–120 hours after chemotherapy) are the most difficult to control. National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) antiemesis-guideline recommendations for HEC include a four-drug regimen (5HT3 RA, neurokinin 1 [NK1] RA, dexamethasone, and olanzapine). For some MEC regimens, a three-drug regimen (5HT3 RA, NK1 RA, and dexamethasone) is recommended. While 5HT3 RAs have dramatically improved CINV in the acute phase (0–24 hours after chemotherapy), their efficacy declines in the delayed phase. Newer formulations have been developed to extend 5HT3-RA efficacy into the delayed phase. Granisetron extended-release subcutaneous (GERSC), the most recently approved 5HT3 RA, provides slow, controlled release of therapeutic granisetron concentrations for ≥5 days. GERSC is included in the NCCN and ASCO guidelines for MEC and HEC, with NCCN-preferred status for MEC in the absence of an NK1 RA. Efficacy and safety of 5HT3 RAs in the context of guideline-recommended antiemetic therapy are reviewed. Conclusion: Recent updates in antiemetic guidelines and the development of newer antiemetics should help mitigate CINV, this dreaded side effect of chemotherapy. GERSC, the most recently approved 5HT3-RA formulation, is indicated for use with other antiemetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of MEC and anthracycline–cyclophosphamide combination-chemotherapy regimens.