Enhancing the effectiveness of the specific serotonin antagonists. Combination antiemetic therapy with dexamethasone

Abstract

Combinations of drugs have become standard therapy for the prevention of vomiting caused by anticancer drugs like cisplatin. Recently, a new class of antiemetic agents, the potent and specific 5-HT3 receptor antagonists such as ondansetron, granisetron, and tropisetron, have been shown to be more effective and better tolerated than metoclopramide. This report describes the rationale for combination antiemetic therapy, details the testing of metoclopramide-based regimens as a model for combination therapy development, reviews completed trials of ondansetron plus dexamethasone, and offers strategies to further alleviate vomiting during anticancer chemotherapy. The reported trials testing metoclopramide-based combinations were reviewed and that experience was applied to the ongoing studies of ondansetron when used with dexamethasone and other agents. Combinations of metoclopramide, dexamethasone, and lorazepam prevented acute emesis caused by high-dose cisplatin in 63% of patients, lessened side effects, and were convenient enough to administer to outpatients. Completed trials of ondansetron and dexamethasone demonstrated improved vomiting control over ondansetron alone while using less cumbersome schedules. Attempts to improve ondansetron-based antiemetic regimens by developing optimal drug doses and schedules and adding adjuvant and different classes of antiemetic agents are now in clinical testing. Based on previous experience and current results, combinations of a specific serotonin agonist and dexamethasone are the best treatment for prevention of vomiting induced by chemotherapy. Future clinical research should aim to refine antiemetic regimens and improve emetic control through the use of new antiemetic and adjuvant agents.