POTENTIAL FOR COMBINATION THERAPY WITH THE NEW ANTISEROTONERGIC AGENTS

Appreciation of the major role played by serotonergic (5-HT3) neuroreceptors in the emetic reflex arc has introduced an additional factor into the rational design of combination antiemetic therapy. Combinations of an antidopaminergic agent and a corticosteroid have previously served as the basis for many successful antiemetic regimens. Three pilot studies and three randomised studies have now demonstrated potentiation of antiemetic activity of a 5-HT3 antagonist by dexamethasone as well. Further development of combination antiemetic regimens may involve antagonism of additional receptors including those for benzodiazepines, opiates, and catecholamines. Even antidopaminergic agents may continue to have a role. Although high-dose metoclopramide has both antiserotonergic and antidopaminergic activity, other pure antidopaminergic agents retain significant antiemetic activity. The combination of an antiserotonergic agent and a low-dose antidopaminergic agent has already shown promise in one pilot study. Newer and more effective antiemetic combinations will be needed to continue to improve the quality of life of patients receiving chemotherapy.