一项关于局部晚期食管和胃食管交界处癌围手术期同步化疗、吉非替尼和超分割放疗后序贯维持吉非替尼治疗的 II 期研究。

A phase II study of perioperative concurrent chemotherapy, gefitinib, and hyperfractionated radiation followed by maintenance gefitinib in locoregionally advanced esophagus and gastroesophageal junction cancer.

机构信息

Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.

出版信息

J Thorac Oncol. 2010 Feb;5(2):229-35. doi: 10.1097/JTO.0b013e3181c5e334.

DOI:10.1097/JTO.0b013e3181c5e334

PMID:20009775

Abstract

BACKGROUND

Concurrent chemoradiotherapy (CCRT) for locoregionally advanced esophageal or gastroesophageal junction cancer produces high locoregional control rates but suboptimal distant metastatic control (DMC) and overall survival. This phase II study added gefitinib (G) to our previously tested CCRT regimen in an effort to improve these outcomes.

METHODS

Eligibility required T3, N1, or M1a esophageal or gastroesophageal junction squamous cell or adenocarcinoma staged by esophageal ultrasound and positron emission tomography/computed tomography. Four-day continuous intravenous infusions of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) began on day 1 of preoperative radiation (30 Gy and 1.5 Gy bid). Surgery followed in 4 to 6 weeks, and an identical course of CCRT 6 to 10 weeks postoperatively. G 250 mg/d was given with preoperative CCRT for 4 weeks and restarted with postoperative therapy for 2 years. Results were retrospectively compared with our historical series of 93 patients given CCRT without G.

RESULTS

Between April 2003 and July 2006, 80 patients were enrolled. Patient and tumor characteristics were similar to our historical series. G did not increase toxicity except for development of rash in 42 (53%) and diarrhea in 44 (55%) 3-year Kaplan-Meier estimates (G versus non-G treated patients) included: overall survival (42% versus 28%, p = 0.06), DMC (40% versus 32%, p = 0.33), and locoregional control (76% versus 77%, p = 0.74). Intolerance for G maintenance occurred in 48% of patients. Patients who experienced G related diarrhea appeared to have improved outcomes.

CONCLUSIONS

Although G did not worsen CCRT toxicity, maintenance therapy proved difficult. This contemporary cohort of patients enjoyed superior survival, which does not solely reflect a decrease in DMC and merits further investigation.

摘要

背景

局部晚期食管或胃食管交界处癌的同期放化疗（CCRT）可产生较高的局部区域控制率，但远处转移控制（DMC）和总体生存率不理想。本Ⅱ期研究在我们之前测试的 CCRT 方案中加入了吉非替尼（G），以努力改善这些结果。

方法

入选标准要求 T3、N1 或 M1a 期食管或胃食管交界处的鳞状细胞癌或腺癌，通过食管超声和正电子发射断层扫描/计算机断层扫描分期。顺铂（20mg/m/d）和氟尿嘧啶（1000mg/m/d）的 4 天连续静脉输注于术前放疗第 1 天（30Gy 和 1.5Gy 每日 2 次）开始。4 至 6 周后进行手术，术后 6 至 10 周进行相同的 CCRT 疗程。G 250mg/d 在术前 CCRT 时使用 4 周，术后治疗时重新开始使用 2 年。结果与我们未使用 G 的 93 例接受 CCRT 的历史系列进行回顾性比较。

结果

2003 年 4 月至 2006 年 7 月，共纳入 80 例患者。患者和肿瘤特征与我们的历史系列相似。除了 42 例（53%）出现皮疹和 44 例（55%）出现腹泻外，G 并未增加毒性。3 年的 Kaplan-Meier 估计值（G 与未接受 G 治疗的患者）包括：总生存率（42%对 28%，p=0.06）、DMC（40%对 32%，p=0.33）和局部区域控制（76%对 77%，p=0.74）。48%的患者不能耐受 G 维持治疗。出现 G 相关腹泻的患者似乎有更好的结局。