Rapoport Bernardo, van Eeden Ronwyn, Smit Teresa
a The Medical Oncology Centre of Rosebank , Johannesburg , South Africa.
Expert Rev Clin Pharmacol. 2017 Jan;10(1):17-29. doi: 10.1080/17512433.2017.1266251. Epub 2016 Dec 15.
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. Although sustained antiemetic control across repeated chemotherapy cycles is important for cancer treatment continuation, few studies have investigated the efficacy of antiemetic prophylaxis over multiple chemotherapy cycles. Areas covered: Here we discuss the use of antiemetic hydroxytryptamine type 3 (5-HT) receptor and neurokinin (NK)-1 receptor antagonists for prevention of CINV, limiting our review to clinical trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1 receptor antagonist rolapitant. 5-HT receptor antagonists may be effective in controlling CINV over repeated chemotherapy cycles, but evidence comes primarily from noncomparative studies. NK-1 receptor antagonists provide increased protection against CINV but differences in endpoint selection and methods of analysis preclude meaningful comparisons between agents. Rolapitant shows sustained control of emesis and nausea over multiple cycles of chemotherapy, and compared to other NK-1 receptor antagonists, has a longer half-life and reduced potential for cytochrome P450 3A4-mediated drug-drug interactions. Expert commentary: Trial design should be a key consideration in future studies of CINV therapies, including analytical methods utilized, choice of endpoints, and methods for accounting for nonresponders and patient attrition over multiple cycles of chemotherapy.
化疗引起的恶心和呕吐(CINV)是许多细胞毒性化疗方案的一种使人衰弱的副作用。尽管在重复化疗周期中持续控制恶心呕吐对于癌症治疗的持续进行很重要,但很少有研究调查多周期化疗中预防性止吐的疗效。涵盖领域:在此,我们讨论使用5-羟色胺3型(5-HT)受体拮抗剂和神经激肽(NK)-1受体拮抗剂预防CINV,我们的综述仅限于多周期化疗背景下的临床试验,重点关注NK-1受体拮抗剂罗拉匹坦。5-HT受体拮抗剂在重复化疗周期中可能有效控制CINV,但证据主要来自非对照研究。NK-1受体拮抗剂可增强对CINV的防护,但终点选择和分析方法的差异妨碍了不同药物之间进行有意义的比较。罗拉匹坦在多周期化疗中显示出对呕吐和恶心的持续控制,并且与其他NK-1受体拮抗剂相比,具有更长的半衰期以及细胞色素P450 3A4介导的药物相互作用可能性降低。专家评论:试验设计应是未来CINV治疗研究的关键考虑因素,包括所采用的分析方法、终点选择以及处理多周期化疗中无反应者和患者损耗的方法。