title: Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial.
abstract: 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.
authors: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Lauren M
authors: LM
authors: Postlewait
authors: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Cecilia G
authors: CG
authors: Ethun
authors: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: David A
authors: DA
authors: Kooby
authors: Division of General Surgery, Department of Surgery, Emory University, Atlanta, Georgia.
authors: Juan M
authors: JM
authors: Sarmiento
authors: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors: Zhengjia
authors: Z
authors: Chen
authors: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Charles A
authors: CA
authors: Staley
authors: Department of Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Edith
authors: E
authors: Brutcher
authors: Department of Pathology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Volkan
authors: V
authors: Adsay
authors: Department of Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Bassel
authors: B
authors: El-Rayes
authors: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Shishir K
authors: SK
authors: Maithel
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004720:Endonucleases / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D000093542:Gemcitabine
keywords: ERCC1; adjuvant chemotherapy; pancreatic ductal adenocarcinoma; predictive markers; recurrence; survival