Department of Gastrointestinal Endoscopy, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Gastrointest Endosc. 2018 Apr;87(4):1126-1131. doi: 10.1016/j.gie.2017.10.030. Epub 2017 Nov 6.
Carbohydrate sulfotransferase 15 (CHST15) promotes tumor growth and invasion and is considered to be an emergent therapeutic target for pancreatic cancer. The aim of this study was to evaluate the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, the double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer.
Six patients with unresectable pancreatic cancer, treated at Tokyo Metropolitan Geriatric Hospital, were used in this open-labeled, investigator-initiated trial. A total of 16 mL STNM01 (250 nM) was injected into the tumor through EUS-FNI. The study's primary endpoint was safety, with a secondary endpoint of tumor response 4 weeks after the initial injection. Some patients received a series of infusions as extensions. The local expression of CHST15 and overall survival (OS) were also evaluated.
There were no adverse events. The mean tumor diameter changed from 30.7 to 29.3 mm 4 weeks after injection. Four patients exhibited necrosis of tumor in biopsy specimens. CHST15 was highly expressed at baseline, with 2 patients showing large reductions of CHST15 at week 4. The mean OS of these 2 patients was 15 months, whereas it was 5.7 months for the other 4 patients.
EUS-FNI of STNM01 in pancreatic cancer is safe and feasible. The CHST15 reduction could predict tumor progression and OS. Injections of STNM01 during the beginning of treatment may reduce CHST15 and warrants further investigation.
碳水化合物硫酸转移酶 15（CHST15）促进肿瘤生长和侵袭，被认为是胰腺癌的一个新的治疗靶点。本研究旨在评估 EUS 引导下细针注射（EUS-FNI）STNM01 的安全性和疗效，STNM01 是一种特异性抑制 CHST15 的双链 RNA 寡核苷酸，用于治疗胰腺癌患者。
本研究为一项开放性、研究者发起的临床试验，共纳入东京都老年病医院收治的 6 例不可切除的胰腺癌患者。通过 EUS-FNI 将 16mL 的 STNM01（250nM）注入肿瘤。研究的主要终点是安全性，次要终点是初次注射后 4 周的肿瘤反应。部分患者进行了一系列输注作为扩展。还评估了局部 CHST15 表达和总生存期（OS）。
无不良事件发生。注射后 4 周，平均肿瘤直径从 30.7 毫米缩小至 29.3 毫米。4 例患者活检标本显示肿瘤坏死。基线时 CHST15 高表达，其中 2 例患者在第 4 周时 CHST15 明显减少。这 2 例患者的中位 OS 为 15 个月，而另外 4 例患者的中位 OS 为 5.7 个月。
EUS-FNI 注射 STNM01 治疗胰腺癌是安全可行的。CHST15 减少可能预测肿瘤进展和 OS。在治疗开始时注射 STNM01 可能会降低 CHST15，值得进一步研究。
