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

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


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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Autophagy / drug effects*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Humans
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Progression-Free Survival
  • Risk Factors
  • Survival Analysis
  • Survivors


  • Deoxycytidine
  • Hydroxychloroquine
  • Gemcitabine

Supplementary concepts

  • Pancreatic Carcinoma