Aapro Matti
Clinique de Genolier, 1272, Genolier, Switzerland.
Curr Med Res Opin. 2005 Jun;21(6):885-97. doi: 10.1185/030079905X46313.
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.
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.
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.
5-HT3受体拮抗剂问世后，化疗或放疗引起的呕吐的管理有了显著改善。鉴于这些药物与皮质类固醇联合使用，推荐预防性使用以预防化疗和放疗引起的恶心和呕吐。尽管有这些进展，但恶心和呕吐仍然是细胞毒性治疗最令人恐惧和衰弱的不良反应之一。癌症患者群体向老龄化转变对支持性护理提出了更多考虑因素，重点是在控制恶心和呕吐的同时，尽量减少毒性并避免药物相互作用。本综述介绍了优化止吐治疗时需要考虑的一些关键问题。使用PubMed搜索引擎搜索相关文献（截至2004年12月）以及2003年和2004年期间收集的相关国际会议资料。
虽然恶心和呕吐的早期阶段是由5-羟色胺介导的，但已确定P物质在晚期呕吐中起作用，这促使了NK1受体拮抗剂阿瑞匹坦的研发。作为一种新药，阿瑞匹坦的临床特征仍在探索中，包括其与同时使用的药物的相互作用。急性和迟发性急性恶心和呕吐得到良好控制的患者出现延迟发作症状的风险降低，这强调了使用有效药物进行预防性管理的重要性。尽管5-HT3受体拮抗剂被广泛认为具有同等疗效，但它们的半衰期和受体拮抗性质各不相同。它们的代谢特征也不同，细胞色素P450（CYP）代谢影响它们发生药物相互作用的倾向。有几套指南概述了止吐治疗选择和使用的建议。然而据报道，放疗和化疗环境中5-HT3受体拮抗剂的使用不足，一些常用剂量可能不是最理想的。
在优化止吐治疗时，需要更广泛地实施指南，并考虑每个患者的个体需求。支持性护理药物的安全性和耐受性应是关键考虑因素，应充分考虑心血管方面的警告以及药物相互作用的可能性，特别是鉴于癌症患者群体的老龄化。
