Optimising antiemetic therapy: what are the problems and how can they be overcome?

Background: Management of chemotherapy- or radiotherapy-induced emesis has improved significantly following the introduction of the 5-HT3-receptor antagonists. Prophylactic use of these agents is recommended for the prevention of both chemotherapy- and radiotherapy-induced nausea and vomiting, given with a corticosteroid. Despite these advances, nausea and vomiting remain among the most feared and debilitating adverse effects of cytotoxic therapy. The shift towards a more elderly population of patients with cancer presents additional considerations for supportive care, with an emphasis on achieving control of nausea and vomiting, whilst minimising toxicity and avoiding drug-drug interactions. This review presents some of the key issues for consideration in optimising antiemetic therapy. The PubMed search engine was used to search for relevant literature (up to December 2004) and relevant international congress materials collected during 2003 and 2004. Scope: While the early stages of nausea and vomiting are 5-HT-mediated, identification of a role for substance P in late emesis has led to the development of the NK1-receptor antagonist, aprepitant. As a new agent, the clinical profile of aprepitant is still being explored, including its interaction with concomitant medications. Patients who achieve good control of acute and late-acute nausea and vomiting have a reduced risk of experiencing delayed onset symptoms, emphasising the importance of prophylactic management with effective agents. Although the 5-HT3-receptor antagonists are widely considered to have equivalent efficacy, they vary in half-life and the nature of antagonism at receptors. Their metabolic profiles also differ, with cytochrome P450 (CYP) metabolism affecting their propensity for drug-drug interactions. Several sets of guidelines are available that outline recommendations for selection and use of antiemetic therapy. However, under-use of 5-HT3-receptor antagonists has been reported in both the radiotherapy and chemotherapy settings, and some commonly used doses may be suboptimal. Conclusion: In optimising antiemetic therapy, wider implementation of guidelines is desirable, as is consideration of each patient's individual needs. Safety and tolerability of supportive care medications should be a key consideration, and cardiovascular warnings and the possibility of drug-drug interactions should be given sufficient consideration, particularly in view of the older age of the population with cancer.