No abstract

No abstract

Many patients with cancer receive multiple chemotherapy agents as well as other medications for coexisting medical conditions. Despite the introduction of 5-HT3 receptor antagonists, the management of nausea and vomiting following cancer treatment and after cancer surgery remains complex, particularly when patients are receiving multiple prescription medications. As a drug class, the 5-HT3 receptor antagonists have good antiemetic efficacy and an improved safety profile over conventional antiemetics. Nevertheless, pharmacologic differences exist between these agents, such as their interaction with the metabolic cytochrome P450 system. This review examines the major metabolic differences between the most frequently prescribed 5-HT3 receptor antagonists, dolasetron, granisetron, ondansetron, and tropisetron. The potential drug interactions that these differences may precipitate and key genetic interindividual variations in drug metabolism are also considered. To avoid or minimize potential drug interactions, the 5-HT3 receptor antagonist with the lowest risk of these interactions should be considered as first choice.

5-HT3-receptor antagonists are the current antiemetic 'gold standard' for chemotherapy- and radiotherapy-induced nausea and vomiting. Interestingly, studies have shown that patients experiencing poor control of acute chemotherapy-induced nausea and vomiting with one antiemetic therapy may respond well to another agent, including a drug of the same class. This review examines pharmacological differences between the 5-HT3-receptor antagonists in order to determine potential reasons for their differing efficacy, particularly in relation to refractory emesis. Differences in drug metabolism by the cytochrome P450 system, inadequate dosing of the respective agents, differences in onset and duration of action, and effects on serotonin release and reuptake are discussed.

BACKGROUNDNausea and emesis as a consequence of chemotherapy or radiotherapy can have an adverse effect on patients' quality of life during cancer treatment and may last for > 5 days after administration. Guidelines suggest that, used at appropriate doses, the 5‐hydroxytryptamine type‐3 (5‐HT3) receptor antagonists—which are considered the antiemetic “gold standard” when they are administered in combination with corticosteroids—demonstrate equivalent efficacy and safety. However, due to financial considerations, these agents often are used at lower doses than recommended.METHODSA literature review of relevant publications pertaining to the control of chemotherapy‐induced nausea and emesis and dosing issues of the 5‐HT3 receptor antagonists was undertaken to provide a comprehensive review of dosing issues relevant to the 5‐HT3 receptor antagonists.RESULTSThe issue of “down dosing” was particularly pertinent because of the nature of the 5‐HT3 receptor antagonist dose‐response curve: A steep dose‐response profile within a narrow dose range suggests that antiemetic control will be lost suddenly after dose deescalation. However, the array of predisposing and confounding patient factors indicates that it is unlikely that a loss of antiemetic control will be apparent across a population; rather, individuals will experience loss of control as the dose is reduced below threshold. Of the 4 5‐HT3 receptor antagonists currently licensed in the United States (granisetron, ondansetron, dolasetron, and palonosetron), ondansetron is used sometimes at lower than optimal doses, and there is evidence to suggest that even the approved oral dose of dolasetron may be suboptimal.CONCLUSIONSSuboptimal dosing not only will be detrimental to patients' quality of life but, ultimately, will prove counterproductive in terms of hospital resources, and it will add to the already significant socioeconomic burden associated with cancer therapy. Therefore, the dose of antiemetic agent administered should be sufficiently high to ensure good emesis control across the whole patient population. Cancer 2005. © 2005 American Cancer Society.