title: SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma.
abstract: OBJECTIVE
  The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen.
  
  
  METHODS
  Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m(2) intravenously on days 1 and 8) and capecitabine (1,500 mg/m(2) per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m(2) per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively.
  
  
  RESULTS
  A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage.
  
  
  CONCLUSIONS
  This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY. edgar.ben-josef@uphs.upenn.edu.
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Guthrie
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: El-Khoueiry
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lowy
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Thomas
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Micetich
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Thomas
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Abby B
authors.initials: AB
authors.lastname: Siegel
authors.affiliation: Edgar Ben-Josef, University of Pennsylvania, Philadelphia, PA; Katherine A. Guthrie, Fred Hutchinson Cancer Research Center, Seattle, WA; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Andrew M. Lowy, University of California San Diego Moores Cancer Center, La Jolla, CA; Christopher L. Corless, Oregon Health and Science University Knight Diagnostic Laboratories; Charles R. Thomas Jr and Charles D. Blanke, Oregon Health and Science University Knight Cancer Institute, Portland, OR; Mark M. Zalupski, University of Michigan, Ann Arbor, MI; Steven R. Alberts, Mayo Clinic, Rochester, MN; Laura A. Dawson, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Kenneth C. Micetich, Loyola University Medical Center, Maywood, IL; Melanie B. Thomas, Medical University of South Carolina, Charleston, SC; and Abby B. Siegel, Columbia University, New York, NY.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017734:Bile Ducts, Extrahepatic / Q000473:pathology; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine