Kris M G, Baltzer L, Pisters K M, Tyson L B
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Cancer. 1993 Dec 1;72(11 Suppl):3436-42. doi: 10.1002/1097-0142(19931201)72:11+<3436::aid-cncr2820721610>3.0.co;2-z.
Combinations of drugs have become standard therapy for the prevention of vomiting caused by anticancer drugs like cisplatin. Recently, a new class of antiemetic agents, the potent and specific 5-HT3 receptor antagonists such as ondansetron, granisetron, and tropisetron, have been shown to be more effective and better tolerated than metoclopramide. This report describes the rationale for combination antiemetic therapy, details the testing of metoclopramide-based regimens as a model for combination therapy development, reviews completed trials of ondansetron plus dexamethasone, and offers strategies to further alleviate vomiting during anticancer chemotherapy. The reported trials testing metoclopramide-based combinations were reviewed and that experience was applied to the ongoing studies of ondansetron when used with dexamethasone and other agents. Combinations of metoclopramide, dexamethasone, and lorazepam prevented acute emesis caused by high-dose cisplatin in 63% of patients, lessened side effects, and were convenient enough to administer to outpatients. Completed trials of ondansetron and dexamethasone demonstrated improved vomiting control over ondansetron alone while using less cumbersome schedules. Attempts to improve ondansetron-based antiemetic regimens by developing optimal drug doses and schedules and adding adjuvant and different classes of antiemetic agents are now in clinical testing. Based on previous experience and current results, combinations of a specific serotonin agonist and dexamethasone are the best treatment for prevention of vomiting induced by chemotherapy. Future clinical research should aim to refine antiemetic regimens and improve emetic control through the use of new antiemetic and adjuvant agents.
药物联合已成为预防顺铂等抗癌药物所致呕吐的标准疗法。近来，一类新型止吐药，即强效且特异的5-羟色胺3（5-HT3）受体拮抗剂，如昂丹司琼、格拉司琼和托烷司琼，已显示出比胃复安更有效且耐受性更好。本报告阐述了联合止吐疗法的基本原理，详细介绍了以胃复安为基础的治疗方案作为联合疗法开发模型的测试情况，回顾了昂丹司琼加地塞米松的已完成试验，并提供了在抗癌化疗期间进一步减轻呕吐的策略。对报告的以胃复安为基础的联合治疗试验进行了回顾，并将该经验应用于昂丹司琼与地塞米松及其他药物联合使用的正在进行的研究中。胃复安、地塞米松和劳拉西泮联合使用可使63%的患者预防高剂量顺铂所致的急性呕吐，减轻副作用，且方便门诊患者给药。昂丹司琼和地塞米松的已完成试验表明，与单独使用昂丹司琼相比，呕吐控制得到改善，且给药方案更简便。目前正在进行临床试验，试图通过制定最佳药物剂量和给药方案以及添加辅助药物和不同类别的止吐药来改进以昂丹司琼为基础的止吐方案。基于以往经验和当前结果，特定5-羟色胺激动剂与地塞米松联合使用是预防化疗所致呕吐的最佳治疗方法。未来的临床研究应旨在通过使用新型止吐药和辅助药物来优化止吐方案并改善呕吐控制。
