DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study.

Sang Myung Woo,Woo Jin Lee,Sung-Sik Han,Ju Hee Lee,Sang-Jae Park,Eun Young Park,Eun Kyung Hong,Yun-Hee Kim,Weon Seo Park,Tae Hyun Kim,Jungnam Joo,Kyong-Ah Yoon

doi:10.18632/oncotarget.19037

Sang Myung Woo, Woo Jin Lee + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.19037

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Journal: Oncotarget	Publication Date: Jul 6, 2017
Citations: 14	License type: cc-by

Affiliation: National Cancer Center, Konkuk University

Abstract

The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry. This study enrolled 72 patients with BTC (26 with gallbladder cancer, 33 with extrahepatic cholangiocarcinoma, and 13 with intrahepatic cholangiocarcinoma). The 2-year recurrence-free survival (RFS) rate was 43% (95% CI, 33–57%). Multivariable analysis showed that DCK expression, vascular invasion, and lymph node metastasis were significantly associated with RFS. Twenty-one (31.8%) were positive for DCK immunoreactivity. The median RFS was 34.95 months for DCK-positive patients, compared with 11.41 months for DCK-negative patients. Although the primary hypothesis of this study, defined as a 2-year RFS of 60%, was not met, intratumoral DCK expression was significantly associated with RFS in patients with resected BTC treated with postoperative gemcitabine chemotherapy. Future randomized controlled trials are warranted.

Highlights

Biliary tract cancer (BTC) has been defined as all tumors arising from the biliary tract or the biliary drainage system, including the intra- and extrahepatic bile ducts and the gallbladder
The primary hypothesis of this study, defined as a 2-year recurrence-free survival (RFS) of 60%, was not met, intratumoral DCK expression was significantly associated with RFS in patients with resected biliary tract cancer (BTC) treated with postoperative gemcitabine chemotherapy
Several clinical studies have reported that intratumoral levels of human equilibrative nucleoside transporter 1, the major transporter responsible for gemcitabine uptake into cells, and of ribonucleotide reductase subunit 1 (RRM1) have predictive significance for survival in BTC patients treated with adjuvant gemcitabine therapy [10,11,12,13]

Summary

INTRODUCTION

Biliary tract cancer (BTC) has been defined as all tumors arising from the biliary tract or the biliary drainage system, including the intra- and extrahepatic bile ducts and the gallbladder. Several clinical studies have reported that intratumoral levels of human equilibrative nucleoside transporter 1 (hENT1), the major transporter responsible for gemcitabine uptake into cells, and of ribonucleotide reductase subunit 1 (RRM1) have predictive significance for survival in BTC patients treated with adjuvant gemcitabine therapy [10,11,12,13]. We analyzed eight single nucleotide polymorphisms (SNPs) of five genes to determine the relationships between these SNPs and clinical outcome in BTC patients treated with gemcitabine-based chemotherapy

RESULTS

DISCUSSION

Study design and patients