EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy and concurrent external beam radiation before surgery for localized or locoregional esophageal cancer: a multicenter prospective randomized trial
EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy and concurrent external beam radiation before surgery for localized or locoregional esophageal cancer: a multicenter prospective randomized trial
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DOI：
10.1016/j.gie.2016.11.017
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发表时间：
2017-07-01
影响因子：
7.7
通讯作者：
Fowers, Kirk
中科院分区：
文献类型：
--
作者：
DeWitt, John M.;Murthy, S. Krishna;Fowers, Kirk
背景和目标：OncoGel（Protherics湖城公司，湖城，UT）是紫杉醇（PTX），配制在热敏性、可生物降解的共聚物中，用于集中细胞毒性和放射增敏。一项2a期研究表明，EUS引导下的PTX注射到随后接受放疗的食管肿瘤中是安全的。在一项国际多中心、前瞻性、随机化2b期研究中，患有食管/胃食管连接部的局部或局部区域腺癌或鳞状细胞癌（SCC）并且在手术前适合接受新辅助放化疗（CRT）的患者被随机分配至标准治疗（SOC）加EUS-引导的PTX注射或单独的SOC。在整个肿瘤中以0.5至1.0 mL等份注射PTX。计划的CRT SOC为前4天（第1周和第5周）静脉注射5-氟尿嘧啶，每个5-氟尿嘧啶疗程的第1天静脉注射顺铂，并在5.5周内进行放疗。CRT期间每周对患者进行评估，并在12周时重新评估手术资格和CT总体肿瘤体积的变化。结果：分析包括137例患者（97例男性;平均年龄58 ± 9.1岁），通过使用改良的意向治疗方法随机分配至PTX+SOC（n=72）和SOC（n=65）。PTX组（12.5%）和SOC组（20.0%; P=.24;比值比，0.57; 95%置信区间，0.23-1.44）的肿瘤体积总体缓解率相似。SOC组的病理完全缓解率较高（26.2% vs 12.5%; P=.046）;然而，12个月生存率（P=.412）和1起或多起不良事件的总体频率（P= 0.17）两组之间相似。SOC + PTX是安全的，但不会改善食管局部或局部区域癌患者的总生存期或原发肿瘤部位的总体肿瘤缓解。胃食管连接处（临床试验注册号：NCT 00573131。）
Background and Aims: OncoGel (Protherics Salt Lake City, Inc, Salt Lake City, UT) is paclitaxel (PTX) formulated in a thermosensitive, biodegradable copolymer for focused cytotoxicity and radiosensitization. A phase 2a study suggested that EUS-guided PTX injection into esophageal tumors subsequently receiving radiotherapy was safe.Methods: In an international multicenter, prospective, randomized phase 2b study, patients with local or locoregional adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus/gastroesophageal junction and eligible for neoadjuvant chemoradiotherapy (CRT) before surgery were randomized to standard of care (SOC) plus EUS-guided PTX injection or SOC alone. PTX was injected in 0.5 to 1.0 mL aliquots throughout the tumor. Planned CRT as SOC was intravenous 5-fluorouracil for the first 4 days (weeks 1 and 5), intravenous cisplatin on the first day of each 5-fluorouracil course, and radiotherapy over 5.5 weeks. Patients were evaluated weekly during CRT and re-evaluated at 12 weeks for surgical eligibility and CT for change in overall tumor volume.Results: The analysis included 137 patients (97 males; mean age, 58 +/- 9.1 years) randomized to PTX+SOC (n=72) and SOC (n=65) by using a modified intention-to-treat approach. Overall response by tumor volume between the PTX (12.5%) and the SOC group (20.0%; P=.24; odds ratio, 0.57; 95% confidence interval, 0.23-1.44) was similar. Pathologic complete response was higher in the SOC group (26.2% vs 12.5%; P=.046); however, 12-month survival (P=.412) and the overall frequency of 1 or more adverse events (P=.17) were similar between the 2 groups.Conclusions: SOC + PTX is safe but does not improve overall survival or overall tumor response at the primary tumor site for patients with local or locoregional cancer of the esophagus/gastroesophageal junction. (Clinical trial registration number: NCT00573131.)