Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation of Smad4(Dpc4) Immunostaining With Pattern of Disease Progression

• Published in: Journal of clinical oncology Vol. 29; no. 22; pp. 3037 - 3043
• Main Authors: Crane, Christopher H., Varadhachary, Gauri R., Yordy, John S., Staerkel, Gregg A., Javle, Milind M., Safran, Howard, Haque, Waqar, Hobbs, Bridgett D., Krishnan, Sunil, Fleming, Jason B., Das, Prajnan, Lee, Jeffrey E., Abbruzzese, James L., Wolff, Robert A.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.08.2011
• Subjects: Actuarial Analysis; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma - radiotherapy; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cetuximab; Chemotherapy, Adjuvant; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease Progression; Drug Administration Schedule; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gemcitabine; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Neoplasm Staging; Organoplatinum Compounds - administration & dosage; Original Reports; Oxaliplatin; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - radiotherapy; Patient Selection; Radiotherapy, Adjuvant; Remission Induction; Research Design; Smad4 Protein - metabolism; Treatment Outcome; Tumors; Antineoplastic agent; Immunohistochemistry; Smad protein; Gemcitabine; Monoclonal antibody; Epidermal growth factor receptor; Cancerology; Oxaliplatin; Pancreas cancer; Phase II trial; Cetuximab; Pyrimidine nucleoside; Pancreatic disease; Platinum II Complexes; Malignant tumor; Radiotherapy; Alkylating agent; Anatomic pathology; Chemotherapy; Treatment; Antimetabolic; Pyrimidine derivatives; Digestive diseases; Combined treatment; Locally advanced stage; Fluorine Organic compounds; Pancreas adenocarcinoma; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2010.33.8038

This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.