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

To discuss new therapeutic strategies for chemotherapy-induced nausea and vomiting (CINV) involving 5-hydroxytryptamine type 3 (5HT₃)-receptor antagonists (RAs).

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.

Recent updates in antiemetic guidelines and the development of newer antiemet-ics 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.