Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil With Bevacizumab in Patients With Metastatic Gastroesophageal Adenocarcinoma
Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil With Bevacizumab in Patients With Metastatic Gastroesophageal Adenocarcinoma
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DOI：
10.1200/jco.2010.32.0770
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发表时间：
2011-03-01
影响因子：
45.3
通讯作者：
Kelsen, David P.
中科院分区：
文献类型：
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作者：
Shah, Manish A.;Jhawer, Minaxi;Kelsen, David P.
目的评价多西紫杉醇、顺铂和氟尿嘧啶(MDCF)联合贝伐单抗治疗晚期胃食管腺癌的安全性和有效性。患者和方法未经治疗的转移性胃食管腺癌患者给予贝伐单抗10 mg/kg，多西紫杉醇40 mg/m(2)，氟尿嘧啶400 mg/m(2)，亚叶酸钙400 mg/m(2)，第1天开始静脉滴注，氟尿嘧啶1000 mg/m(2)/d×2天持续静脉滴注，顺铂40 mg/m(2)，第3天。主要目标是将加用贝伐单抗的6个月无进展生存率(PFS)从既往DCF对照组的43%提高到63%。结果从2006年10月至2008年10月，共有44例符合条件的癌症患者入选，其中胃22例，胃食道交界处20例，食道2例。在39例可测量疾病的患者中，确认有效率为67%(95%可信区间，50%至81%)。6个月的PFS为79%(95%CI，63%~88%)，中位PFS为12个月(95%CI，8.8~18.2个月)。随访26个月，中位总生存期为16.8个月(95%可信区间为12.1~26.1个月)，2年生存率为37%。与治疗相关的3~4级毒性反应如下：无发热的中性粒细胞减少(50%)、乏力(25%)、静脉血栓栓塞症(39%)、恶心、呕吐、粘膜炎、神经病变和发热性中性粒细胞减少(均小于10%)。在亚组分析中，弥漫性胃癌的PFS和OS显著恶化，近端/GEJ肿瘤的有效率为85%(95%CI，62%~97%)。结论MDCF联合贝伐单抗治疗进展期胃食管腺癌是可以耐受的，具有显著的患者预后。6个月的PFS为79%，超过了我们预定义的疗效终点，中位数和2年OS分别为16.8个月和37%。J Clin Oncol29：868-874(C)2010年美国临床肿瘤学会
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/m(2), fluorouracil 400 mg/m(2), leucovorin 400 mg/m(2) on day 1, fluorouracil 1,000 mg/m(2)/d x 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m(2) 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. J Clin Oncol 29: 868-874. (C) 2010 by American Society of Clinical Oncology