Weinstein C, Jordan K, Green S A, Camacho E, Khanani S, Beckford-Brathwaite E, Vallejos W, Liang L W, Noga S J, Rapoport B L
Merck & Co., Inc., Kenilworth, NJ, USA
Department of Hematology/Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Ann Oncol. 2016 Jan;27(1):172-8. doi: 10.1093/annonc/mdv482. Epub 2015 Oct 8.
To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC.
In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25-120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0-120 and 0-24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points.
The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated.
Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population.
NCT01594749 (https://clinicaltrials.gov/ct2/show/NCT01594749).
为确立神经激肽-1（NK1）受体拮抗剂（RA）在以非蒽环类药物和环磷酰胺（AC）为基础的中度致吐性化疗（MEC）方案中的止吐治疗作用，本研究评估了单剂量静脉注射（i.v.）福沙匹坦预防与非AC MEC相关的化疗引起的恶心和呕吐（CINV）。
在这项国际III期双盲试验中，计划在第1天接受≥1次非AC MEC的成年癌症受试者被随机分配至包含第1天单剂量静脉注射150 mg福沙匹坦或安慰剂以及昂丹司琼和地塞米松的方案；对照方案接受者在第2天和第3天接受昂丹司琼。主要终点是在延迟期（MEC开始后25 - 120小时）达到完全缓解（CR；无呕吐且未使用救援药物）的受试者比例和安全性。次要终点包括在总体期和急性期（分别为MEC开始后0 - 120小时和0 - 24小时）的CR以及总体期无呕吐。恶心和功能生活指数 - 呕吐被评估为探索性终点。
与对照组相比，福沙匹坦方案在延迟期（78.9%对68.5%；P < 0.001）和总体期（77.1%对66.9%；P < 0.001）显著改善了CR，但在急性期未改善（93.2%对91.0%；P = 0.184）。在总体期，福沙匹坦方案无呕吐（82.7%对72.9%；P < 0.001）和无明显恶心（83.2%对77.9%；P = 0.030）的受试者比例也显著提高。福沙匹坦方案总体耐受性良好。
添加到5 - HT3 RA和地塞米松中的单剂量福沙匹坦耐受性良好，并显示出对与非AC MEC相关的CINV的卓越控制（达到主要终点）。这是第一项在明确的非AC MEC人群中评估NK1 RA疗法作为静脉制剂的研究。
NCT01594749（https://clinicaltrials.gov/ct2/show/NCT01594749）。
Zotero 插件