PMID- 36531683
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221222
IS  - 2364-3722 (Print)
IS  - 2196-9736 (Electronic)
IS  - 2196-9736 (Linking)
VI  - 10
IP  - 12
DP  - 2022 Dec
TI  - Early phase trial of intracystic injection of large surface area microparticle 
      paclitaxel for treatment of mucinous pancreatic cysts.
PG  - E1517-E1525
LID - 10.1055/a-1949-7730 [doi]
AB  - Background and study aims  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. Patients and methods  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. Results  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. Conclusions  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.
CI  - The Author(s). This is an open access article published by Thieme under the terms 
      of the Creative Commons Attribution-NonDerivative-NonCommercial License, 
      permitting copying and reproduction so long as the original work is given 
      appropriate credit. Contents may not be used for commercial purposes, or adapted, 
      remixed, transformed or built upon. 
      (https://creativecommons.org/licenses/by-nc-nd/4.0/).
FAU - Othman, Mohamed
AU  - Othman M
AD  - Gastroenterology and Hepatology Section, Baylor College of Medicine Medical 
      Center, Houston, Texas, United States.
FAU - Patel, Kalpesh
AU  - Patel K
AD  - Gastroenterology and Hepatology Section, Baylor College of Medicine Medical 
      Center, Houston, Texas, United States.
FAU - Krishna, Somashekar G
AU  - Krishna SG
AD  - Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University 
      Wexner Medical Center, Columbus, Ohio, United States.
FAU - Mendoza-Ladd, Antonio
AU  - Mendoza-Ladd A
AD  - Division of Gastroenterology, Texas Tech University Health Sciences Center at El 
      Paso, El Paso, Texas, United States.
FAU - Verco, Shelagh
AU  - Verco S
AD  - US Biotest, Inc., San Luis Obispo, California, United States.
FAU - Abidi, Wasif
AU  - Abidi W
AD  - Gastroenterology and Hepatology Section, Baylor College of Medicine Medical 
      Center, Houston, Texas, United States.
FAU - Verco, James
AU  - Verco J
AD  - US Biotest, Inc., San Luis Obispo, California, United States.
FAU - Wendt, Alison
AU  - Wendt A
AD  - US Biotest, Inc., San Luis Obispo, California, United States.
FAU - diZerega, Gere
AU  - diZerega G
AD  - US Biotest, Inc., San Luis Obispo, California, United States.
AD  - NanOlogy, LLC., Fort Worth, Texas, United States.
LA  - eng
PT  - Journal Article
DEP - 20221215
PL  - Germany
TA  - Endosc Int Open
JT  - Endoscopy international open
JID - 101639919
PMC - PMC9754881
COIS- Competing interests Gere diZerega holds a consultant/advisory role, has stock 
      ownership or receives funding from NanOlogy, LLC. Shelagh Verco, James Verco, and 
      Alison Wendt are full-time employees of NanOlogy, LLC. Mohamed O Othman is a 
      consultant for Abbvie, BSC, Olympus, Conmed, Apollo and Nestle and received grant 
      funding from Abbvie, Lucid Diagnostics, Conmed and NanOlogy, LLC. Kalpesh Patel 
      is a consultant for Conmed and Abbvie. Somashekar G. Krishna is PI of an 
      investigator-initiated study in part funded by a grant to The Ohio State 
      University Wexner Medical Center from Mauna Kea Technologies, Paris, France. The 
      remaining authors declare that they have no conflict of interest.
EDAT- 2022/12/20 06:00
MHDA- 2022/12/20 06:01
PMCR- 2022/12/01
CRDT- 2022/12/19 03:57
PHST- 2022/04/19 00:00 [received]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/12/19 03:57 [entrez]
PHST- 2022/12/20 06:00 [pubmed]
PHST- 2022/12/20 06:01 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - 10.1055/a-1949-7730 [doi]
PST - epublish
SO  - Endosc Int Open. 2022 Dec 15;10(12):E1517-E1525. doi: 10.1055/a-1949-7730. 
      eCollection 2022 Dec.