Division of Oncology, Washington University School of Medicine in St Louis, St Louis, Missouri.
Division of Public Health Sciences, Washington University School of Medicine in St Louis, St Louis, Missouri.
JAMA Oncol. 2020 Aug 1;6(8):1231-1240. doi: 10.1001/jamaoncol.2020.2020.
Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers.
To evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced gastroesophageal adenocarcinoma.
DESIGN, SETTING, AND PARTICIPANTS: This is an open-label, single-arm phase 2 study of first-line FOLFIRINOX in patients with advanced gastroesophageal adenocarcinoma. Estimated sample size included 41 patients with ERBB2-negative disease with 90% power to detect an ORR of 60% or greater with α of .10. No enrollment goal was planned for ERBB2-positive patients, but they were allowed to receive trastuzumab in combination with FOLFIRINOX.
Starting doses were fluorouracil, 400 mg/m2 bolus, followed by 2400 mg/m2 over 46 hours; leucovorin, 400 mg/m2; irinotecan, 180 mg/m2; and oxaliplatin, 85 mg/m2. Trastuzumab was administered as a 6 mg/kg loading dose, followed by 4 mg/kg every 14 days in patients with ERBB2-positive disease.
The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS), and duration of response.
From November 2013 to May 2018, 67 patients were enrolled (median [range] age, 59.0 [34-78] years; including 56 [84%] men), and 26 of 67 (39%) had ERBB2-positive disease. Median follow-up was 17.4 months. The ORR was 61%(95% CI, 44.5%-75.8%) (25 of 41) in the ERBB2-negative group and 85% (95% CI, 65.1%-95.6%) (22 of 26) in the ERBB2-positive group, including 1 patient with complete response. For ERBB2-negative patients, median PFS was 8.4 months and median OS was 15.5 months; for ERBB2-positive patients, median PFS was 13.8 months and median OS was 19.6 months. Fifty-six patients (84%) had dose modifications or treatment delays. The most common toxic effects were neutropenia (91%, n = 61), diarrhea (63%, n = 42), peripheral sensory neuropathy (61%, n = 41), and nausea (48%, n = 32), with no unexpected toxic effects.
The FOLFIRINOX regimen with or without trastuzumab was associated with improved ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status.
ClinicalTrials.gov Identifier: NCT01928290.
转移性胃食管腺癌患者的标准一线治疗方案的客观缓解率（ORR）约为 40%。对于其他胃肠道癌症，如胰腺癌和结肠癌，奥沙利铂、亚叶酸钙、氟尿嘧啶和伊立替康（FOLFIRINOX）联合方案已被证明是有效的一线治疗方法。
评估 FOLFIRINOX 作为晚期胃食管腺癌一线治疗的临床疗效和安全性。
设计、设置和参与者：这是一项开放标签、单臂 2 期研究，评估了晚期胃食管腺癌患者的一线 FOLFIRINOX 治疗。预计包括 41 例 ERBB2 阴性疾病患者，样本量为 41 例，有 90%的效能检测到 60%或更高的 ORR，α 值为 0.10。对于 ERBB2 阳性患者，没有计划纳入目标人数，但允许他们接受曲妥珠单抗联合 FOLFIRINOX 治疗。
起始剂量为氟尿嘧啶 400mg/m2 推注，随后 46 小时内持续输注 2400mg/m2；亚叶酸钙 400mg/m2；伊立替康 180mg/m2；奥沙利铂 85mg/m2。曲妥珠单抗的初始剂量为 6mg/kg，然后在 ERBB2 阳性疾病患者中每 14 天 4mg/kg。
主要终点是根据实体瘤反应评估标准 1.1 评估的 ORR。次要终点包括安全性特征、无进展生存期（PFS）、总生存期（OS）和缓解持续时间。
从 2013 年 11 月至 2018 年 5 月，共纳入 67 例患者（中位年龄 [范围]，59.0 [34-78]岁；包括 56 [84%]例男性），其中 26 例（39%）为 ERBB2 阳性疾病。中位随访时间为 17.4 个月。在 ERBB2 阴性组中，ORR 为 61%（95%CI，44.5%-75.8%）（25/41），在 ERBB2 阳性组中为 85%（95%CI，65.1%-95.6%）（22/26），包括 1 例完全缓解。对于 ERBB2 阴性患者，中位 PFS 为 8.4 个月，中位 OS 为 15.5 个月；对于 ERBB2 阳性患者，中位 PFS 为 13.8 个月，中位 OS 为 19.6 个月。56 例（84%）患者进行了剂量调整或治疗延迟。最常见的毒性作用是中性粒细胞减少（91%，n=61）、腹泻（63%，n=42）、周围感觉神经病变（61%，n=41）和恶心（48%，n=32），没有意外的毒性作用。
在一线治疗中，含或不含曲妥珠单抗的 FOLFIRINOX 方案可提高晚期胃食管腺癌患者的 ORR 和 PFS。对于体力状况良好的患者，该方案可能是一种合理的治疗选择。
ClinicalTrials.gov 标识符：NCT01928290。
