A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Herbert J ZehMichael T Lotze

Abstract

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 (P = 0.00016), compared with control. In patients with elevated CA 19-9, a return to normal was associated with improved overall and recurrence-free survival (P < 0.0001). There were no differences in serious adverse events between arms and chemotherapy dose number was equivalent. The PGH arm had greater ...Continue Reading

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Citations

May 8, 2020·Nature·Keisuke YamamotoAlec C Kimmelman
Sep 4, 2020·Cancers·Lydie M O BarbeauKasper M A Rouschop
Nov 10, 2020·Autophagy·Jingbo LiDaolin Tang
Jan 9, 2021·Journal of Immunotherapy·Carolina Mendonça GorgulhoMichael T Lotze
Feb 4, 2021·Proceedings of the National Academy of Sciences of the United States of America·Subhadip MukhopadhyayAlec C Kimmelman
Oct 24, 2020·Trends in Pharmacological Sciences·Andrei-Florian StoicaSiim Pauklin
Mar 21, 2021·Nature Reviews. Gastroenterology & Hepatology·Joel Encarnación-Rosado, Alec C Kimmelman
Mar 25, 2021·Nature Reviews. Cancer·Houjun XiaWeiping Zou
Jan 29, 2021·Cancer Discovery·Prasenjit DeyRonald A DePinho
May 17, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Sahib ZadaDeok Ryong Kim
Jul 13, 2021·Cancer Medicine·Chirayu MohindrooFlorencia McAllister
Jul 19, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Yuanyang WangWeibin Wang
Jul 28, 2021·Cancer Letters·Giuseppa AugelloMelchiorre Cervello
Aug 1, 2021·Nature Reviews. Gastroenterology & Hepatology·Xin ChenDaolin Tang
Aug 7, 2021·Pharmaceuticals·Alessandro Di FedericoGiovanni Brandi
Oct 1, 2021·Drug Discovery Today·Jacob CuylerXiang-Qun Xie
Nov 4, 2021·Expert Opinion on Investigational Drugs·Byung Woog Kang, Ian Chau

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