Encouraging long-term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high-risk patients with resectable pancreatic carcinoma.
Cancer Med
; 10(20): 7233-7241, 2021 10.
Article
in En
| MEDLINE
| ID: mdl-34559451
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Autophagy
/
Antineoplastic Combined Chemotherapy Protocols
/
Deoxycytidine
/
Hydroxychloroquine
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cancer Med
Year:
2021
Document type:
Article
Affiliation country:
United States