Rubenstein Edward B, Slusher Barbara S, Rojas Camilo, Navari Rudolph M
Division of Medical and Scientific Affairs, MGI Pharma, Bloomington, Minnesota 55437, USA.
Cancer J. 2006 Sep-Oct;12(5):341-7. doi: 10.1097/00130404-200609000-00003.
Nausea and vomiting are considered to be among the most distressing consequences of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV), including ondansetron, granisetron, and dolasetron. These agents provide significant improvement in the management of acute emesis but are ineffective at preventing delayed emesis. In 2003, a new 5-HT(3) receptor antagonist, palonosetron HCL (Aloxi), was introduced to the U.S. market. Palonosetron was found to be effective in preventing delayed CINV. Indeed, palonosetron was the first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention of both acute and delayed CINV. More recently, studies on the role of substance P in the emetic process led to the development of aprepitant (Emend) for the prevention of delayed emesis in combination with 5-HT(3) receptor antagonists. Despite these major advances, CINV remains uncontrolled in some patients. Current efforts are focused on treating refractory emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the emetic pathway. Ongoing work in pharmacogenomics has postulated several candidate genes that could be involved in emetic sensitivity and responsiveness to antiemetic therapy. Investigations into the pharmacogenomics of CINV may someday be able to aid in the identification of high risk patients and patients unlikely to respond to conventional therapies.
恶心和呕吐被认为是细胞毒性化疗最令人痛苦的后果之一。目前，有几种新型5 - HT(3)受体拮抗剂用于治疗化疗引起的恶心和呕吐（CINV），包括昂丹司琼、格拉司琼和多西拉敏。这些药物在急性呕吐的治疗方面有显著改善，但在预防延迟性呕吐方面无效。2003年，一种新的5 - HT(3)受体拮抗剂盐酸帕洛诺司琼（Aloxi）被引入美国市场。发现帕洛诺司琼在预防延迟性CINV方面有效。事实上，帕洛诺司琼是美国食品药品监督管理局（FDA）批准的第一种也是唯一一种用于预防急性和延迟性CINV的5 - HT(3)受体拮抗剂。最近，关于P物质在呕吐过程中作用的研究导致了阿瑞匹坦（Emend）的开发，用于与5 - HT(3)受体拮抗剂联合预防延迟性呕吐。尽管取得了这些重大进展，但在一些患者中CINV仍然无法得到有效控制。目前的努力集中在治疗难治性呕吐上，包括对用于其他适应症的化合物进行临床评估以及对靶向呕吐途径中其他递质的新型分子进行临床前评估。药物基因组学方面正在进行的工作推测了几个可能参与呕吐敏感性和对抗呕吐治疗反应性的候选基因。对CINV药物基因组学的研究有朝一日可能有助于识别高危患者和不太可能对传统疗法产生反应的患者。
