Lee Schwartzberg, MD
The goal of selecting optimal antiemetic therapy continues to be a moving target with the emergence of newer agents and patient-related risk factors, as well as the rapid evolution of guidelines for the management of chemotherapy-induced nausea and vomiting (CINV). Utilizing an appropriate degree of prophylaxis for the first cycle of chemotherapy is critical to prevent breakthrough CINV, which is difficult to manage and can lead to later anticipatory vomiting during subsequent cycles of therapy. Optimizing antiemetic usage requires awareness of available and emerging agents, as well as of the unique characteristics of these therapies that affect their role in CINV management.
5-HT3 Receptor Antagonists
The first-generation 5-HT3 receptor antagonists (RAs; ondansetron, granisetron, dolasetron [Anzemet], and tropisetron [Navoban]) revolutionized the management of CINV in terms of efficacy and safety compared with historical antiemetics (eg, metoclopramide [Reglan]).1
These agents exhibit comparable efficacy, preventing 50% to 80% of acute CINV in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) regimens and are considered equivalent in CINV guidelines. Despite their efficacy against acute CINV, these agents are much less effective at preventing delayed CINV.
In contrast, the second-generation 5-HT3 RA, palonosetron (Alexi), demonstrates efficacy in preventing both acute and delayed CINV. Palonosetron plus dexamethasone has demonstrated superiority over the first-generation 5-HT3 RAs plus dexamethasone.1,2
These advantages result from the unique pharmacodynamic properties of palonosetron, including a longer half-life and higher receptor binding affinity compared with the first-generation 5-HT3 RAs. In addition, binding of palonosetron to the 5-HT3 receptor creates positive cooperativity that results in further palonosetron binding and eventual receptor internalization, blocking 5-HT3 signaling and crosstalk with neurokinin-1 (NK-1) receptor signaling.3,4
A novel extended-release subcutaneous formulation of granisetron, APF530, was recently approved by the FDA for CINV.5
A unique biopolymer delivery system provides sustained release to improve the therapeutic concentration of granisetron over an extended period (>5 days).
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