Adra Nabil, Albany Costantine, Brames Mary J, Case-Eads Somer, Johnson Cynthia S, Liu Ziyue, Fausel Christopher A, Breen Timothy, Hanna Nasser H, Hauke Ralph J, Picus Joel, Einhorn Lawrence H
Division of Hematology/Oncology, Melvin & Bren Simon Cancer Center, Indiana University School of Medicine, 535 Barnhill Drive, RT 400, Indianapolis, IN, 46202, USA.
Department of Biostatistics, Indiana University, Indianapolis, IN, USA.
Support Care Cancer. 2016 Jul;24(7):2837-42. doi: 10.1007/s00520-016-3100-y. Epub 2016 Feb 2.
A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen.
GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1-5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate-no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %.
Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %).
The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917.
一项III期研究在接受5天顺铂联合化疗的生殖细胞肿瘤（GCT）患者中，于5-羟色胺3型受体拮抗剂（5HT3-RA）加地塞米松的基础上加用阿瑞匹坦，结果显示完全缓解（CR）有显著改善（《临床肿瘤学杂志》30:3998 - 4003, 2012）。在单日顺铂化疗中，磷丙泊酚二钠与阿瑞匹坦相比已证明具有非劣效性，且已被批准作为单剂量替代药物。这项单臂II期研究是评估磷丙泊酚二钠在接受多日顺铂方案患者中的首个临床试验。
纳入接受5天顺铂联合化疗的GCT患者。在第3天和第5天静脉给予150mg磷丙泊酚二钠。给予5HT3-RA第1 - 5天（若为帕洛诺司琼，则在第1、3和5天）加地塞米松第1天和第2天20mg，第6、7和8天口服4mg，每日两次。允许使用解救性止吐药。主要目标是确定CR率——无呕吐发作或使用解救药物。计划招募64例患者，预期CR＞27%。
共纳入65例患者，其中54例符合分析条件。中位年龄为33岁。51例患者接受了博来霉素、依托泊苷和顺铂（BEP）化疗。13例（24.1%）患者观察到CR（95%阿格雷斯蒂 - 库尔二项式置信区间14.5%，37.1%）。
与我们之前的III期研究相比，这项II期研究的数据似乎表明用磷丙泊酚二钠替代阿瑞匹坦时CR率较低。尚不清楚在多日顺铂化疗中用磷丙泊酚二钠替代阿瑞匹坦是否能提供与单日顺铂化疗相同的益处。试验注册 临床试验信息NCT01736917。
