Oncotarget

Clinical Research Papers:

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

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Oncotarget. 2017; 8:81394-81404. https://doi.org/10.18632/oncotarget.19037

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Abstract

Sang Myung Woo1, Kyong-Ah Yoon2, Eun Kyung Hong1,3, Weon Seo Park3, Sung-Sik Han1, Sang-Jae Park1, Jungnam Joo4, Eun Young Park4, Ju Hee Lee1, Yun-Hee Kim5, Tae Hyun Kim1 and Woo Jin Lee1

1Center for Liver Cancer, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea

2College of Veterinary Medicine, Konkuk University, Seoul, Korea

3Department of Pathology, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea

4Biometrics Research Branch, Research Institute, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea

5Molecular Imaging Branch, Research Institute, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea

Correspondence to:

Sang Myung Woo, email: wsm@ncc.re.kr

Woo Jin Lee, email: lwj@ncc.re.kr

Keywords: biliary tract cancer, gemcitabine, adjuvant therapy, chemotherapy

Received: March 03, 2017     Accepted: June 18, 2017     Published: July 06, 2017

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.


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