From the Division of Interventional Oncology and Surgical Endoscopy, Parkview Cancer Institute, Fort Wayne, IN.
Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA.
Pancreas. 2023 Mar 1;52(3):e179-e187. doi: 10.1097/MPA.0000000000002236.
Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC).
Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months. Paclitaxel pharmacokinetics were evaluated, imaging at 3 and 6 months determined tumor response, and multiplex immunofluorescence was conducted to characterize local immune response.
Most treatment-emergent adverse events were attributed to LAPC. Plasma paclitaxel levels were negligible. Eight subjects' tumors became resectable after IT LSAM-PTX, and 5 of 6 (83%) were resected with R0. Multiplex immunofluorescence of resected tumors demonstrated increased T cells, natural killer cells, and macrophages and decreased myeloid-derived suppressor cells. Six-month disease control rate was 94%, and median overall survival was 19.7 months in the 2-injection subjects. For nonresected and resected groups, overall survival times were 18.9 and 35.2 months, respectively.
Neoadjuvant IT LSAM-PTX, in combination with SOC, was well tolerated and may provide benefits to LAPC patients, evidenced by enhanced immune response, improved disease control rate, restaging leading to surgery, and extended survival.
大表面积微球紫杉醇（LSAM-PTX）提供了一种肿瘤内（IT）化疗储库。本研究评估了经内镜超声细针注射给予不可切除局部晚期胰腺癌（LAPC）患者 IT LSAM-PTX 的安全性、耐受性和肿瘤反应。
10 名受试者在剂量递增阶段接受治疗，另外 22 名受试者接受间隔 4 周的 15mg/ml LSAM-PTX 治疗 2 次，共 12 个月。评估了紫杉醇的药代动力学，在 3 个月和 6 个月进行影像学检查以确定肿瘤反应，并进行了多重免疫荧光检测以评估局部免疫反应。
大多数治疗相关不良事件归因于 LAPC。血浆紫杉醇水平可忽略不计。8 名患者的肿瘤经 IT LSAM-PTX 后变得可切除，其中 6 名患者中有 5 名（83%）实现了 R0 切除。对切除肿瘤的多重免疫荧光分析表明，T 细胞、自然杀伤细胞和巨噬细胞增加，髓系来源抑制细胞减少。6 个月疾病控制率为 94%，2 次注射组的中位总生存期为 19.7 个月。对于未切除和切除组，总生存时间分别为 18.9 个月和 35.2 个月。
新辅助 IT LSAM-PTX 联合 SOC 具有良好的耐受性，并可能为 LAPC 患者带来获益，表现为增强免疫反应、提高疾病控制率、重新分期导致手术以及延长生存时间。
