title: CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers.
abstract: To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data.
  
  
  
  Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma.
  
  
  
  This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death.
  
  
  
  In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested.
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH. peter_enzinger@dfci.harvard.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Enzinger
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Barbara Ann
authors.initials: BA
authors.lastname: Burtness
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Kathe
authors.initials: K
authors.lastname: Douglas
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: David H
authors.initials: DH
authors.lastname: Ilson
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Victoria Meucci
authors.initials: VM
authors.lastname: Villaflor
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Alan
authors.initials: A
authors.lastname: Venook
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Al Bowen
authors.initials: AB
authors.lastname: Benson
authors.affiliation: Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University, Durham, NC; David H. Ilson, Memorial Sloan Kettering Cancer Center and Alliance for Clinical Trials in Oncology, New York, NY; Victoria Meucci Villaflor, University of Chicago Medicine and Alliance for Clinical Trials in Oncology; Al Bowen Benson III, Northwestern University Feinberg School of Medicine, Chicago, IL; Alan Venook, University of California San Francisco Helen Diller Family Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, San Francisco, CA; and Richard M. Goldberg, Ohio State University James Comprehensive Cancer Center and Alliance for Clinical Trials in Oncology, Columbus, OH.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D000068818:Cetuximab / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D015251:Epirubicin; D000077146:Irinotecan; D000068818:Cetuximab; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin