Fifty Years of Antiemetic in Chemotherapy-Induced Nausea and Vomiting
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Abstract
Chemotherapy-induced nausea and vomiting (CINV), is the most common side effect in cancer patients. Development of antiemetic drugs for CINV over the last 50 years has focused on combination of antiemetic regimen. Antiemetic drugs that predominantly use are dopamine receptor antagonists, 5HT3-receptor antagonists (5HT3-RAs), NK1-receptor antagonists (NK1-RAs), corticosteroids and olanzapine. Olanzapine, an atypical antipsychotic, is now increasingly uses as an off-label indication for CINV. Patients receiving chemotherapy with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) require combination antiemetic regimens for prevention of acute CINV that usually occurs within 24 hours. Furthermore, it can prevent delayed CINV, occurs after chemotherapy treatment more than 24 hours. The first antiemetic drugs which recommended in CINV was phenothiazine, it has been used since the 1970s. In the 1980s, high doses metoclopramide has been widely used because it has more antiemetic effect, but provides more severe side effects. Later in the year of 1990s, the first-generation of 5HT3-RAs including ondansetron, dorasetron and, granisetron were approved, respectively. However, they have no difference of antiemetic effect, but some drugs may cause QT prolongation. In 2003, the second-generation of 5HT3-RAs was approved. Palanosetron was proved that has better pharmacodynamics and pharmacokinetics than the first-generation, so it has more efficacy for prevention of delayed CINV. In the same period, aprepitant-the first drug of NK1-RAs was approved. In 2014 and 2015, netupitant and rolapitant were approved respectively. Netupitant is one of fixed-drug combination, NEPA that consist of netupitant and palanosetron. Netupitant and aprepitant are CPY3A4 inhibitors. Rolapitant are CYP2A6, BRCP, and P-gp inhibitors. So using NK1-RAs with other drugs should be concern about drug interactions. Antiemetic regimens for HEC are four-drugs combination (olanzapine, NK1-RAs, 5HT3-RAs, and dexamethasone) or three-drugs combination namely olanzapine-based (olanzapine, 5HT3-RAs, and dexamethasone) NK1-RAs-based (NK1-RAs, 5HT3-RAs, and dexamethasone). Recommended antiemetics regimen in MEC are two-drugs combination (5HT3-RAs and dexamethasone) or three-drugs combination particularly olanzapine-based and NK1-RAs-based.
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