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Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial
Author(s) -
Postlewait Lauren M.,
Ethun Cecilia G.,
Kooby David A.,
Sarmiento Juan M.,
Chen Zhengjia,
Staley Charles A.,
Brutcher Edith,
Adsay Volkan,
ElRayes Bassel,
Maithel Shishir K.
Publication year - 2016
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.24317
Subject(s) - ercc1 , medicine , gemcitabine , adenocarcinoma , cisplatin , oncology , neutropenia , stage (stratigraphy) , adjuvant therapy , gastroenterology , chemotherapy , cancer , nucleotide excision repair , dna repair , paleontology , biochemistry , chemistry , biology , gene
Background Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001; OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted in increased PFS for advanced and metastatic disease, which may be predicted by low expression of excision repair cross‐complementing group–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor ERCC1 expression. Methods Patients with resected PDAC were enrolled (2010–2013) and received Gem(1,000 mg/m 2 )/Cis(50 mg/m 2 ). Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low or high expression. Primary outcomes were recurrence‐free and overall survival (RFS/OS). Results Of 22 pts, 16(73%) were Stage IIB, 5(23%) Stage IIA, and 1(4%) Stage IA. Grade 3/4 toxicity occurred in 13 pts (59%); neutropenia was most common (n = 9;41%). Median follow‐up was 37.5 months. Median RFS was 16.7 mo; OS was 35.5 mo. Low ERCC1 (n = 15;75%) compared to high ERCC1 (n = 5;25%) was not associated with improved RFS (12.4 vs. 16.7 mo; P = 0.68) or OS (Median not reached vs. 21.6 mo; P = 0.22). Conclusions Adjuvant Gem/Cis is feasible in patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in most patients. J. Surg. Oncol. 2016;114:336–341 . © 2016 Wiley Periodicals, Inc.