Tailored adjuvant gemcitabine versus 5-fluorouracil/folinic acid based on hENT1 immunohistochemical staining in resected pancreatic ductal adenocarcinoma: A biomarker stratified prospective trial.

Abstract

BACKGROUND:

The study aimed to evaluate the clinical outcomes of tailored adjuvant chemotherapy according to human equilibrative nucleoside transporter 1 (hENT1) expression in resected pancreatic ductal adenocarcinoma (PDA).

METHODS:

Patients who underwent pancreatectomy for PDA were enrolled prospectively. According to intra-tumoral hENT1 expression, the high hENT1 (≥50%) group received gemcitabine and the low hENT1 (<50%) group received 5-fluorouracil plus folinic acid (5-FU/FA). The propensity score-matched control consisted of patients who received hENT1-independent adjuvant chemotherapy. The primary outcome was recurrence free survival (RFS) and the secondary outcomes were overall survival (OS) and toxicities.

RESULTS:

Between May 2015 and June 2017, we enrolled 44 patients with resected PDA. During a median follow-up period of 28.5 months, the intention-to-treat population showed much longer median RFS [22.9 (95% CI, 11.3-34.5) vs. 10.9 (95% CI, 6.9-14.9) months, P = 0.043] and median OS [36.2 (95% CI, 26.5-45.9) vs. 22.1 (95% CI, 17.7-26.6) months, P = 0.001] compared to the controls. Among 5 patients in the low hENT1 group who discontinued treatment, 2 patients receiving 5-FU/FA discontinued treatment due to drug toxicities (febrile neutropenia and toxic epidermal necrolysis).

CONCLUSION:

Tailored adjuvant chemotherapy based on hENT1 staining provides excellent clinical outcomes among patients with resected PDA.

CLINICAL TRIAL REGISTRATION:

clinicaltrials.gov identifier: NCT02486497.

• Authors: Dong Woo Shin, Jong-Chan Lee, Jaihwan Kim, Yoo-Seok Yoon, Ho-Seong Han, Haeryoung Kim, Jin-Hyeok Hwang
• Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] (Pancreatology) Vol. 21 Issue 4 Pg. 796-804 (Jun 2021) ISSN: 1424-3911 [Electronic] Switzerland
• PMID: 33795193 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Biomarkers, Tumor
• Equilibrative Nucleoside Transporter 1
• Deoxycytidine
• Leucovorin
• Fluorouracil
• Gemcitabine

Topics

• Biomarkers, Tumor
• Carcinoma, Pancreatic Ductal (drug therapy, surgery)
• Chemotherapy, Adjuvant
• Deoxycytidine (analogs & derivatives)
• Equilibrative Nucleoside Transporter 1
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Pancreatic Neoplasms (drug therapy, surgery)
• Prospective Studies
• Staining and Labeling
• Gemcitabine