Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.
Journal
Pancreas
ISSN: 1536-4828
Titre abrégé: Pancreas
Pays: United States
ID NLM: 8608542
Informations de publication
Date de publication:
01 Mar 2023
01 Mar 2023
Historique:
medline:
2
11
2023
pubmed:
2
10
2023
entrez:
2
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37782888
doi: 10.1097/MPA.0000000000002236
pii: 00006676-990000000-00062
doi:
Substances chimiques
Paclitaxel
P88XT4IS4D
Pancreatic Hormones
0
Banques de données
ClinicalTrials.gov
['NCT03077685']
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e179-e187Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
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.
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