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.