Lauren M Postlewait1, Cecilia G Ethun1, David A Kooby1, Juan M Sarmiento2, Zhengjia Chen3, Charles A Staley1, Edith Brutcher4, Volkan Adsay5, Bassel El-Rayes4, Shishir K Maithel1. 1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia. 2. Division of General Surgery, Department of Surgery, Emory University, Atlanta, Georgia. 3. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia. 4. Department of Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. 5. Department of Pathology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
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.
RCT Entities:
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 tumorERCC1 expression. METHODS:Patients with resected PDAC were enrolled (2010-2013) and received Gem(1,000 mg/m(2) )/Cis(50 mg/m(2) ). TumorERCC1 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. TumorERCC1 expression can be reliably evaluated, and low expression is present in most patients. J. Surg. Oncol. 2016;114:336-341.
Authors: Ishan Roy; Kathleen A Boyle; Emily P Vonderhaar; Noah P Zimmerman; Egal Gorse; A Craig Mackinnon; Rosa F Hwang; Janusz Franco-Barraza; Edna Cukierman; Susan Tsai; Douglas B Evans; Michael B Dwinell Journal: Lab Invest Date: 2017-01-16 Impact factor: 5.662