title: Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234.
abstract: OBJECTIVE
  To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features.
  
  
  METHODS
  Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m(2) or docetaxel 15 mg/m(2) once per week.
  
  
  RESULTS
  Between April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors. Grade 3 to 4 myelosuppression was observed in 28% of patients in the cisplatin arm and 14% in the docetaxel arm; mucositis was observed in 56% and 54%, respectively. DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial (Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck), which had a hazard ratio of 0.76 for the cisplatin arm versus control (P = .05) and 0.69 for the docetaxel arm versus control (P = .01), reflecting absolute improvement in 2-year DFS of 2.5% and 11.1%, respectively.
  
  
  CONCLUSIONS
  The delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial.
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO. harari@humonc.wisc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Harari
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Harris
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Jordan
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Foote
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Machtay
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Marvin
authors.initials: M
authors.lastname: Rotman
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuntia
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: William
authors.initials: W
authors.lastname: Straube
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Paul M. Harari, University of Wisconsin Hospital, Madison, WI; Jonathan Harris and Qiang Zhang, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Merrill S. Kies, Jeffrey N. Myers, and Kian Ang, MD Anderson Cancer Center, Houston, TX; Richard C. Jordan, University of California San Francisco, San Francisco; Deepak Khuntia, Varian Medical Systems, Palo Alto, CA; Maura L. Gillison, The Ohio State University, Columbus; Mitchell Machtay, Case Western Reserve University, Cleveland, OH; Robert L. Foote, Mayo Clinic, Rochester, MN; Marvin Rotman, State University of New York Downstate Medical Center, Brooklyn, NY; and William Straube, Washington University, St. Louis, MO.
authors.forename: Kian
authors.initials: K
authors.lastname: Ang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000068818:Cetuximab; D059186:Chemoradiotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011182:Postoperative Care; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin