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Review
. 2021 Oct;10(20):7233-7241.
doi: 10.1002/cam4.4211. Epub 2021 Sep 24.

Encouraging long-term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high-risk patients with resectable pancreatic carcinoma

Samer S AlMasri  1 , Mazen S Zenati  2 , Annissa Desilva  1 , Ibrahim Nassour  1 , Brian A Boone  3 , Aatur D Singhi  4 , David L Bartlett  5 , Lance A Liotta  6 , Virginia Espina  6 , Patricia Loughran  1 , Michael T Lotze  1   7   8 , Alessandro Paniccia  1 , Herbert J Zeh 3rd  9 , Amer H Zureikat  1 , Nathan Bahary  10
Affiliations
Review

Encouraging long-term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high-risk patients with resectable pancreatic carcinoma

Samer S AlMasri et al. Cancer Med. 2021 Oct.

Abstract

Introduction: Preoperative autophagy inhibition with hydroxychloroquine (HCQ) in combination with gemcitabine in pancreatic adenocarcinoma (PDAC) has been shown to be safe and effective in inducing a serum biomarker response and increase resection rates in a previous phase I/II clinical trial. We aimed to analyze the long-term outcomes of preoperative HCQ with gemcitabine for this cohort.

Methods: A review of patients enrolled between July 2010 and February 2013 in the completed phase I/II single arm (two doses of fixed-dose gemcitabine (1500 mg/m2 ) in combination with oral hydroxychloroquine administered for 31 consecutive days until the day of surgery for high-risk pancreatic cancer) was undertaken. Progression-free survival (PFS) and overall survival analysis (OS) using Kaplan-Meier estimates were performed.

Results: Of 35 patients initially enrolled, 29 patients underwent surgical resection (median age at diagnosis: 62 years, 45% females). Median duration of follow-up was 7.5 years. There was a median 15% decrease in the serum CA19-9 levels following completion of neoadjuvant therapy and 83% of the cohort underwent a pancreaticoduodenectomy, 7 (24%) patients had a concomitant venous resection. On histopathology, 14 (48%) patients had at least a partial treatment response. The median PFS and OS were 11 months (95% Confidence interval [CI]: 7-28) and 31 months (95% CI: 13-47), respectively, while 9 (31%) patients survived beyond 5 years from diagnosis; a rate that compares very favorably with contemporaneous series.

Conclusion: Compared to historical data, neoadjuvant autophagy inhibition with HCQ plus gemcitabine is associated with encouraging long-term survival for patients with PDAC.

Keywords: autophagy; hydroxychloroquine; neoadjuvant; overall survival; pancreatic cancer.

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Conflict of interest statement

None, financial or otherwise.

Figures

FIGURE 1
FIGURE 1
Patient enrollment
FIGURE 2
FIGURE 2
CA19‐9 percentage change in response to neoadjuvant therapy stratified by histopathologic treatment response
FIGURE 3
FIGURE 3
Overall survival (A) and progression‐free survival (B) with the corresponding 1‐, 3‐, and 5‐year percent OS and PFS rates
See this image and copyright information in PMC

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