Anti-emetic therapy in cancer chemotherapy: current status.

Nausea and vomiting are ranked as the most severe side effects to chemotherapy by cancer patients. Twenty years ago, treatment of nausea and vomiting from chemotherapy only had moderate effect and often unpleasant side effects. The drugs used included dopamine(2)-receptor antagonists and corticosteroids alone or combined. This review summarizes the development of anti-emetic therapy, but will focus on the importance of two new classes of anti-emetics: the serotonin(3)- and the neurokinin(1)-receptor antagonists. Furthermore, evidence-based guidelines for the treatment of chemotherapy-induced nausea and vomiting will be given. The serotonin(3)-receptor antagonists, the first group of drugs developed specifically as anti-emetics, have significantly improved the prophylaxis of chemotherapy-induced emesis especially in combination with a corticosteroid. The improvement in the prophylaxis of nausea with this combination is however modest. A new group of anti-emetics, the neurokinin(1)-receptor antagonists, has now been developed, and the first drug, aprepitant, was marketed in 2003. Aprepitant increases the effect of a serotonin(3)-receptor antagonist plus a corticosteroid against acute emesis induced by highly or moderately emetogenic chemotherapy and aprepitant is also active in the protection against delayed emesis. The importance of drug-drug interactions with anti-emetics and other drugs, especially cytotoxins, through their competition for cytochrome P450 enzymes, have been studied. At present, there is no evidence that such interactions are of major clinical importance. Evidence-based clinical guidelines are now available and regularly updated, but unfortunately clinical implementation is slow. Recommendations for some types of chemotherapy-induced emesis such as delayed emesis, is based on a low level of evidence. Furthermore, the majority of clinical trials include highly selected groups of patients not permitting definite conclusions for other and more heterogeneous patient groups. Development of new anti-emetics with other mechanisms of action is awaited with interest.