Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana, USA.
Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India.
Gastrointest Endosc. 2017 Jul;86(1):140-149. doi: 10.1016/j.gie.2016.11.017. Epub 2016 Nov 24.
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.
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.
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.
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.).
OncoGel（Protherics Salt Lake City，Inc，盐湖城，犹他州）是一种紫杉醇（PTX）制剂，采用热敏、可生物降解的共聚物，具有靶向细胞毒性和放射增敏作用。一项 2a 期研究表明，EUS 引导的 PTX 注射到食管肿瘤中，随后接受放射治疗是安全的。
在一项国际多中心、前瞻性、随机 2b 期研究中，患有局部或局部区域腺癌或食管/胃食管交界处鳞状细胞癌（SCC）且有资格接受手术前新辅助放化疗（CRT）的患者被随机分配至标准治疗（SOC）加 EUS 引导的 PTX 注射或 SOC 单独治疗。PTX 以 0.5 至 1.0 毫升的等分剂量注射到整个肿瘤中。计划的 CRT 作为 SOC 是静脉注射氟尿嘧啶 4 天（第 1 周和第 5 周），每氟尿嘧啶疗程第一天静脉注射顺铂，放疗 5.5 周。在 CRT 期间每周评估患者，12 周时评估手术适应证和 CT 以评估总肿瘤体积变化。
采用修改后的意向治疗方法对 137 名患者（97 名男性；平均年龄 58±9.1 岁）进行了随机分组，PTX+SOC（n=72）和 SOC（n=65）。通过肿瘤体积评估，PTX（12.5%）和 SOC 组（20.0%；P=0.24；比值比，0.57；95%置信区间，0.23-1.44）的总体反应相似。SOC 组的病理完全缓解率更高（26.2%比 12.5%；P=0.046）；然而，两组 12 个月生存率（P=0.412）和 1 次或以上不良事件的总体发生率（P=0.17）相似。
SOC+PTX 是安全的，但不能提高局部或局部区域食管/胃食管交界处癌症患者的总生存或原发性肿瘤部位的总体肿瘤反应。（临床试验注册号：NCT00573131。）
