A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients.
Adult
Aged
Aged, 80 and over
Albumins
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Autophagy
/ drug effects
Deoxycytidine
/ administration & dosage
Female
Humans
Hydroxychloroquine
/ administration & dosage
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Paclitaxel
/ administration & dosage
Pancreatic Neoplasms
/ diagnosis
Preoperative Care
/ methods
Recurrence
Survival Analysis
Treatment Outcome
Gemcitabine
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
16
12
2019
revised:
05
02
2020
accepted:
06
03
2020
pubmed:
12
3
2020
medline:
15
9
2021
entrez:
12
3
2020
Statut:
ppublish
Résumé
We hypothesized that autophagy inhibition would increase response to chemotherapy in the preoperative setting for patients with pancreatic adenocarcinoma. We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel. Participants with potentially resectable tumors were randomized to two cycles of nab-paclitaxel and gemcitabine (PG) alone or with hydroxychloroquine (PGH), followed by resection. The primary endpoint was histopathologic response in the resected specimen. Secondary clinical endpoints included serum CA 19-9 biomarker response and margin negative R0 resection. Exploratory endpoints included markers of autophagy, immune infiltrate, and serum cytokines. Thirty-four patients in the PGH arm and 30 in the PG arm were evaluable for the primary endpoint. The PGH arm demonstrated statistically improved Evans grade histopathologic responses ( The addition of hydroxychloroquine to preoperative gemcitabine and nab-paclitaxel chemotherapy in patients with resectable pancreatic adenocarcinoma resulted in greater pathologic tumor response, improved serum biomarker response, and evidence of autophagy inhibition and immune activity.
Identifiants
pubmed: 32156749
pii: 1078-0432.CCR-19-4042
doi: 10.1158/1078-0432.CCR-19-4042
pmc: PMC8086597
mid: NIHMS1576014
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Deoxycytidine
0W860991D6
Hydroxychloroquine
4QWG6N8QKH
Paclitaxel
P88XT4IS4D
Gemcitabine
0
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3126-3134Subventions
Organisme : NCI NIH HHS
ID : R01 CA181450
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206012
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115366
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA160417
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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