Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.
| Autor: | Sharma NR; From the Division of Interventional Oncology and Surgical Endoscopy, Parkview Cancer Institute, Fort Wayne, IN., Lo SK; Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA., Hendifar A; Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA., Othman MO; Gastroenterology and Hepatology Section, Baylor College of Medicine Medical Center, Houston, TX., Patel K; Gastroenterology and Hepatology Section, Baylor College of Medicine Medical Center, Houston, TX., Mendoza-Ladd A; Division of Gastroenterology, Texas Tech University Health Sciences Center at El Paso, El Paso, TX., Verco S; US Biotest, Inc, San Luis Obispo, CA., Maulhardt HA; US Biotest, Inc, San Luis Obispo, CA., Verco J; US Biotest, Inc, San Luis Obispo, CA., Wendt A; US Biotest, Inc, San Luis Obispo, CA., Marin A; US Biotest, Inc, San Luis Obispo, CA., Schmidt CM; Department of Surgery, Indiana University, Indianapolis, IN., diZerega G |
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| Jazyk: | angličtina |
| Zdroj: | Pancreas [Pancreas] 2023 Mar 01; Vol. 52 (3), pp. e179-e187. |
| DOI: | 10.1097/MPA.0000000000002236 |
| Abstrakt: | Objectives: 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). Methods: 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. Results: 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. Conclusions: 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. Competing Interests: These authors disclose the following: N.R.S. is a consultant for Boston Scientific, MedTronic, Mauna Kea, and STERIS and on the advisory board for Endoscopy Now and STERIS. S.K.L. is a consultant for Olympus Inc. A.H. is a consultant or has an advisory role for Novartis, Ipsen, Perthera, Celgene, AbbVie, Esai, and Valar Labs; received research funding from Ipsen and NGM Biopharmaceuticals; received travel, accommodations, and expenses from Halozyme; and has other relationship with FibroGen. M.O.O. is a consultant for Abbvie, BSC, Olympus, Conmed, Apollo, and Nestle and received grant funding from AbbVie, Lucid Diagnostics, Conmed, and NanOlogy, LLC. K.P. is a consultant for Conmed and AbbVie. A.M.-L. is a consultant for Boston Scientific, Olympus, and Conmed and holds a speaker role with Nestle and AbbVie. S.V., H.M., J.V., A.W., and A.M. report being full-time employees of US Biotest Inc. G.d. reports holding a consultant/advisory role, having stock ownership or receiving funding from NanOlogy, LLC. The remaining authors declare no conflict of interest. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.) |
| Databáze: | MEDLINE |
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