Aapro Matti, Blower Peter
Clinique de Genolier, Genolier, Switzerland.
Cancer. 2005 Jul 1;104(1):1-18. doi: 10.1002/cncr.21141.
Nausea 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.
A 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.
The 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.
Suboptimal 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.
化疗或放疗引起的恶心和呕吐会对癌症治疗期间患者的生活质量产生不利影响，且在给药后可能持续超过5天。指南建议，5-羟色胺3型（5-HT3）受体拮抗剂在适当剂量使用时——与皮质类固醇联合使用时被视为止吐“金标准”——具有同等的疗效和安全性。然而，出于经济考虑，这些药物的使用剂量往往低于推荐剂量。
对有关化疗引起的恶心和呕吐控制及5-HT3受体拮抗剂给药问题的相关出版物进行文献综述，以全面回顾与5-HT3受体拮抗剂相关的给药问题。
“降低剂量”问题尤为相关，因为5-HT3受体拮抗剂剂量-反应曲线的性质：在狭窄剂量范围内陡峭的剂量-反应曲线表明，剂量降低后止吐控制将突然丧失。然而，一系列易感和混杂的患者因素表明，在整个人口中不太可能明显出现止吐控制丧失的情况；相反，随着剂量降低到阈值以下，个体将经历控制丧失。在美国目前获批的4种5-HT3受体拮抗剂（格拉司琼、昂丹司琼、多拉司琼和帕洛诺司琼）中，昂丹司琼有时以低于最佳剂量使用，并且有证据表明即使是多拉司琼的获批口服剂量也可能不是最佳的。
次优剂量不仅会损害患者的生活质量，最终还会在医院资源方面适得其反，并会增加已经与癌症治疗相关的巨大社会经济负担。因此，所给予的止吐药剂量应足够高，以确保在全体患者中实现良好的呕吐控制。
