title: Capecitabine as a Radiosensitizer in Adjuvant Chemoradiotherapy for Pancreatic Cancer: A Retrospective Study.
abstract: OBJECTIVE
  Pancreatic cancer remains one of the deadliest cancer diagnoses and is the fourth leading cause of cancer-related deaths in the U.S. Surgery is the mainstay of treatment for the 20% for whom the tumor is resectable, however, controversy exists over the appropriate adjuvant therapy where local recurrence rates remain strikingly high (50-85%). We aimed to evaluate the safety and efficacy of adding capecitabine (a known radiosensitizer by direct and abscopal effects) to concurrent radiation in the adjuvant setting after resection of pancreatic adenocarcinoma.
  
  
  METHODS
  We conducted a retrospective study of 63 patients diagnosed from 2004-2013 with histopathologically-confirmed stage I/II pancreatic cancer treated with a surgical resection followed by adjuvant concurrent chemoradiation to at least 45 Gy using 3D planning and capecitabine at 1,600 mg/m(2)/day (Monday-Friday) for 6 weeks. This was combined with either 4 months of gemcitabine at 1,000 mg/m(2) weekly for 3 out of 4 weeks or capecitabine at 2,000 mg/m(2) for 14 days every 3 weeks for a total of 4 months.
  
  
  RESULTS
  The majority of patients were over 65 years old (71%), male (60%), had negative surgical margins (79%), had pancreatic head or neck involvement (71%), Eastern Cooperative Oncology Group performance score of 1 (71%), and a cancer antigen 19-9 in the range of 11-100 U/ml at the time of diagnosis (51%). Of the 63 patients reviewed, 61 patients (97%) completed concurrent chemoradiotherapy. Treatment was halted in one patient due to gastritis and a second for gastrointestinal bleeding. Otherwise, adverse reactions during concurrent chemoradiotherapy were well-tolerated and the majority were Common Terminology Criteria for Adverse Events grades 1 and 2. Grade 3 toxicity was anorexia (n=2) and hand and foot syndrome (n=2) and GI bleeding (n=1). The only grade 4 toxicities were anorexia (n=1) and fatigue (n=1). The median follow-up of patients at the time of analysis was 36 months. The median survival of the entire cohort was 23.5 (range=8.5-42) months. The 1-, 2- and 3-year survival rates were 80%, 35% and 25%, respectively.
  
  
  CONCLUSIONS
  Concurrent chemoradiation using capecitabine as a radiosensitizer in the adjuvant setting for pancreatic cancer was completed by the vast majority of patients in this series. Treatment was relatively well-tolerated, and its efficacy seems comparable to that for historical controls. This study probably represents the largest yet reported using capecitabine in this setting. Future studies including an increased sample size are required.
authors.affiliation: Tufts University School of Medicine, Tufts Medical Center, Boston, MA, U.S.A.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Abrams
authors.affiliation: Tufts University School of Medicine, Tufts Medical Center, Boston, MA, U.S.A.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Huber
authors.affiliation: Hofstra North Shore LIJ School of Medicine, North Shore LIJ Health System, New Hyde Park, New York, NY, U.S.A.
authors.forename: Jonathan P S
authors.initials: JP
authors.lastname: Knisely
authors.affiliation: Torrance Memorial Medical Center, Torrance, CA, U.S.A.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Chang
authors.affiliation: CWRU School of Medicine, University Hospitals, Cleveland, OH, U.S.A.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Russo
authors.affiliation: Tufts University School of Medicine, Tufts Medical Center, Boston, MA, U.S.A. wsaif@tuftsmedicalcenter.org.
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
mesh_terms: D000368:Aged; D000069287:Capecitabine / Q000009:adverse effects / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D011838:Radiation-Sensitizing Agents; D000069287:Capecitabine
keywords: Chemotherapy; adjuvant therapy; pancreatic neoplasms