Othman Mohamed, Patel Kalpesh, Krishna Somashekar G, Mendoza-Ladd Antonio, Verco Shelagh, Abidi Wasif, Verco James, Wendt Alison, diZerega Gere
Gastroenterology and Hepatology Section, Baylor College of Medicine Medical Center, Houston, Texas, United States.
Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States.
Endosc Int Open. 2022 Dec 15;10(12):E1517-E1525. doi: 10.1055/a-1949-7730. eCollection 2022 Dec.
Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated. Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard "3 + 3" dose-escalation protocol. The highest dose with acceptable safety and tolerability was taken into the confirmatory phase where nine additional subjects received two injections of LSAM-PTX 12 weeks apart. Subjects were followed for 6 months after initial LSAM-PTX treatment for endpoints including: adverse events (AEs), tolerability, pharmacokinetic analysis of systemic paclitaxel drug levels, and change in cyst volume. Nineteen subjects completed the study. No dose-limiting toxicities, treatment-related serious AEs, or clinically significant laboratory changes were reported. Systemic paclitaxel concentrations did not exceed 3.5 ng/mL at any timepoint measured and fell below 1 ng/mL by Week 2, supporting the lack of systemic toxicity. By Week 24 a cyst volume reduction (10-78 %) was seen in 70.6 % of subjects. Intracystic injection of LSAM-PTX into mucinous PCLs resulted in no significant AEs, a lack of systemic absorption, and resulted in reduction of cyst volume over a 6 month period.
黏液性胰腺囊性病变（PCLs）具有恶变潜能，目前唯一公认的治愈方法是手术。一种新型的大表面积微粒紫杉醇（LSAM-PTX）囊内治疗方法可能在不产生局部或全身毒性的情况下治疗PCLs。评估了通过内镜超声引导下细针注射（EUS-FNI）给予LSAM-PTX治疗PCLs的安全性和初步疗效。10例确诊为PCLs（大小>1.5 cm）的受试者按照标准的“3+3”剂量递增方案，通过EUS-FNI接受囊内LSAM-PTX注射，剂量分别为6、10和15 mg/mL，注射体积与从囊肿中抽出的体积相等，分连续队列进行。将具有可接受安全性和耐受性的最高剂量纳入验证阶段，另外9例受试者每隔12周接受两次LSAM-PTX注射。在首次LSAM-PTX治疗后对受试者进行6个月的随访，观察终点包括：不良事件（AE）、耐受性、全身紫杉醇药物水平的药代动力学分析以及囊肿体积变化。19例受试者完成了研究。未报告剂量限制性毒性、与治疗相关的严重AE或具有临床意义的实验室变化。在任何测量时间点，全身紫杉醇浓度均未超过3.5 ng/mL，到第2周时降至1 ng/mL以下，这支持了无全身毒性。到第24周时，70.6%的受试者囊肿体积缩小（10%-78%）。向黏液性PCLs囊内注射LSAM-PTX未导致明显AE，无全身吸收，且在6个月内囊肿体积减小。
