肿瘤化疗所致恶心呕吐的发生机制和药物治疗的研究进展

Advances in mechanism and treatment of chemotherapy-induced nausea and vomiting

化疗所致恶心、呕吐(CINV)是肿瘤患者最常见的不良反应。如果没有镇吐治疗,70%～80%接受化疗的患者会出现恶心、呕吐症状。其程度受化疗药物致吐强弱等多因素的影响。在20世纪90年代5-HT3受体阻滞剂和地塞米松的联合应用使得70%的急性CINV得到了有效的控制。近年来开发了新一代半衰期更长、亲和力更高的5-HT3受体阻滞剂palonosetron(帕洛诺司琼)。此外,随着对P物质和NK-1受体研究的深入以及NK-1受体阻滞剂aprepitant的问世,急性和迟发性CINV的完全缓解率有了进一步提高。根据近年的新进展和NCCN止吐治疗指南新版本的修订,本文综述了CINV的机制和药物治疗的研究进展。

Chemotherapy plays a significant role in the combined therapy of tumour. Chemotherapeutic regimens have improved and are more finely targeted than in the past, but chemotherapy- induced nausea and vomiting （CINV） remains a major obstacle and affects patients＇ satisfaction with treatment. About 70% 80% patients will face CINV without pretreatment. Efforts to improve antiemetic control further are ongoing. Firstgeneration serotonin receptor antagonists combined with dexamethasone greatly improved the control of CINV during the 1990s. The new advancement involves the use of a new 5 - HT3 receptor antagonist （palonosetron） that differs from available serotonin antagonists in its markedly longer half- life （40 h） and greater binding affinity for the type- three serotonin receptor. Another very promising area focuses on substance P as a therapeutic target. Substance P exerts its effects by binding to the neurokinin NK- 1 receptor. Studies with selective NK - 1 antagonists have demonstrated promising antiemetic activity. One agent in this new therapeutic class （aprepitant） recently received regulatory approval in the United States for use in combination with a 5- HT3 antagonist and dexamethasone, defining a new standard of care for highly - emetogenic chemotherapy. This review focuses on the advances in mechanism and treatment of CINV .