贝伐珠单抗联合改良多西紫杉醇、顺铂和氟尿嘧啶治疗转移性胃食管腺癌的 II 期临床研究。
Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.
机构信息
Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, and the Weill School of Medicine, Cornell University, New York, NY, USA.
出版信息
J Clin Oncol. 2011 Mar 1;29(7):868-74. doi: 10.1200/JCO.2010.32.0770. Epub 2010 Dec 28.
PURPOSE
To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies.
PATIENTS AND METHODS
Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates.
RESULTS
In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%).
CONCLUSION
mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.
目的
评估改良多西紫杉醇、顺铂和氟尿嘧啶（mDCF）联合贝伐单抗在晚期胃食管恶性肿瘤患者中的安全性和疗效。
方法
未经治疗的转移性胃食管腺癌患者接受贝伐单抗 10mg/kg、多西紫杉醇 40mg/m²、氟尿嘧啶 400mg/m²、亚叶酸 400mg/m²，第 1 天；氟尿嘧啶 1000mg/m²/d×2 天静脉持续输注，第 1 天开始；顺铂 40mg/m²，第 3 天。主要目标是通过添加贝伐单抗将 6 个月无进展生存率（PFS）从 43%（历史 DCF 对照）提高到 63%。目标入组人数为 44 例，10%的Ⅰ型和Ⅱ型错误率。
结果
2006 年 10 月至 2008 年 10 月期间共纳入 44 例癌症患者：22 例胃癌，20 例胃食管交界处（GEJ），2 例食管。在 39 例可测量疾病患者中，确认的缓解率为 67%（95%CI，50%至 81%）。6 个月 PFS 为 79%（95%CI，63%至 88%），中位 PFS 为 12 个月（95%CI，8.8 至 18.2 个月）。26 个月随访时，中位总生存期（OS）为 16.8 个月（95%CI，12.1 至 26.1 个月），2 年生存率为 37%。与治疗相关的 3 级至 4 级毒性为：无发热性中性粒细胞减少（50%）、疲劳（25%）、静脉血栓栓塞（39%）、恶心、呕吐、黏膜炎、神经病变和发热性中性粒细胞减少各占 10%以下。在亚组分析中，弥漫性胃癌的 PFS 和 OS 明显较差，近端/GEJ 肿瘤的缓解率为 85%（95%CI，62%至 97%）。
结论
mDCF 联合贝伐单抗在晚期胃食管腺癌患者中耐受性良好，且患者获益显著。6 个月 PFS 为 79%，超过我们预先设定的疗效终点，中位和 2 年 OS 分别为 16.8 个月和 37%。
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