Encouraging long‐term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high‐risk patients with resectable pancreatic carcinoma. (24th September 2021) - AlMasri, Samer S.
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/m 2 ) 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. Abstract : Preoperative autophagy inhibition with hydroxychloroquine enhances the therapeutic efficacy of neoadjuvant chemotherapy leading to a sustained and improved survival benefit in high‐risk pancreatic cancer.