Jordan Karin, Blättermann Luisa, Hinke Axel, Müller-Tidow Carsten, Jahn Franziska
Department of Medicine V, Hematology/ Oncology/ Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Department of Internal Medicine IV, Hematology/Oncology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle, Germany.
Support Care Cancer. 2018 Jan;26(1):21-32. doi: 10.1007/s00520-017-3857-7. Epub 2017 Aug 31.
This systematic review evaluates the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic chemotherapy (MEC) excluding anthracycline-cyclophosphamide-based regimens.
A systematic review of MEDLINE (via PubMed and OVID) and Central databases, plus major oncology conferences, identified randomized trials evaluating NK1RAs in combination with a 5-HT RA plus a glucocorticoid for management of CINV. Efficacy endpoints were complete response (CR), no emesis and no nausea rates. Data were analyzed using a random effects model.
Sixteen trials (3848 patients) were identified. Results were separately analyzed for (a) pure MEC regimens (excluding regimens containing carboplatin or oxaliplatin), (b) carboplatin-based regimens, and (c) oxaliplatin-based regimens. (a) Two trials (abstracts) enrolled 715 patients. The odds ratio for overall CR with the addition of an NK1-RA was 1.46 (95% 1.06-2.02; p = 0.02) with an absolute risk difference (RD) of 8%. (b) Nine trials (1790 patients) were identified. The OR for achieving an overall CR was 1.96 (95% CI 1.57-2.45; p < 0.00001) in favor of the NK1RA containing regimen with an RD of 15%. (c) Three trials (1190 patients) were identified. The OR for achieving an overall CR was 1.34 (95% CI 0.88-2.04; p = 0.17) not reaching statistical significance with a RD of 4%.
Clear clinically significant benefit was seen with the addition of NK1RAs in carboplatin-based chemotherapy. A global benefit of an NK1RA containing regimen for the whole MEC category cannot be attested yet and warrants more randomized trials exclusively testing pure MEC regimens without carboplatin.
本系统评价评估了神经激肽-1受体拮抗剂(NK1RAs)在预防除蒽环类-环磷酰胺方案外的中度致吐性化疗(MEC)中化疗引起的恶心和呕吐(CINV)的疗效。
对MEDLINE(通过PubMed和OVID)及Central数据库进行系统评价,并检索主要肿瘤学会议,以确定评估NK1RAs联合5-羟色胺受体拮抗剂(5-HT RA)及糖皮质激素用于管理CINV的随机试验。疗效终点为完全缓解(CR)、无呕吐和无恶心率。采用随机效应模型分析数据。
共纳入16项试验(3848例患者)。结果分别针对(a)单纯MEC方案(不包括含卡铂或奥沙利铂的方案)、(b)含卡铂方案和(c)含奥沙利铂方案进行分析。(a)两项试验(摘要)纳入715例患者。加用NK1-RA后的总体CR优势比为1.46(95% 1.06 - 2.02;p = 0.02),绝对风险差(RD)为8%。(b)确定了9项试验(1790例患者)。含NK1RA方案实现总体CR的优势比为1.96(95% CI 1.57 - 2.45;p < 0.00001),RD为15%。(c)确定了3项试验(1190例患者)。实现总体CR的优势比为1.34(95% CI 0.88 - 2.04;p = 0.17),未达到统计学显著性,RD为4%。
在含卡铂的化疗中加用NK1RAs有明显的临床显著获益。含NK1RA方案对整个MEC类别是否具有整体获益尚未得到证实,需要更多专门针对不含卡铂的单纯MEC方案的随机试验。