title: Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.
abstract: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation.
  
  
  
  This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery.
  
  
  
  Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases.
  
  
  
  The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.
  
  
  
  Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Cleary
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Mamon
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Bueno
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Choi
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Dean M
authors.initials: DM
authors.lastname: Donahue
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.|University of Arizona Cancer Center, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Panos M
authors.initials: PM
authors.lastname: Fidias
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Henning A
authors.initials: HA
authors.lastname: Gaissert
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Jaklitsch
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Kulke
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lynch
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mentzer
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Swanson
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA. peter_enzinger@dfci.harvard.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Enzinger
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068579:Celecoxib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000379:methods*; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000209:etiology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003680:Deglutition Disorders / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D000077146:Irinotecan; D000068579:Celecoxib; D002945:Cisplatin; D002166:Camptothecin
keywords: Chemoradiation; Cyclooxygenase 2 inhibition; Esophageal cancer; Neoadjuvant therapy