Chemotherapy and Radiation Therapy With or Without Surgery in Treating Patients With Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

A Phase III Trial of Concurrent Radiation and Chemotherapy for Advanced Head and Neck Carcinomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047008
• Other study ID #: RTOG 0129
• Secondary ID: CDR0000257233RTO
• Status: Completed
• Phase: Phase 3
• Start date: July 2002
• Est. completion date: May 20, 2022

Study information

• Verified date: April 2023
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways and combining it with chemotherapy before surgery may kill more tumor cells. It is not yet known which radiation therapy regimen combined with chemotherapy with or without surgery is more effective for head and neck cancer. PURPOSE: Randomized phase III trial to compare two different radiation therapy regimens combined with cisplatin with or without surgery in treating patients who have stage III or stage IV head and neck cancer.

Description:

OBJECTIVES: Primary - Compare overall survival of patients with stage III or IV squamous cell carcinoma of the head and neck treated with conventional vs accelerated radiotherapy and concurrent cisplatin with or without surgical resection. Secondary - Compare local-regional control of disease and disease-free rates in patients treated with these regimens. - Compare the acute and late toxicity of these regimens in these patients. - Compare quality of life, perception of side effects, and performance status of patients treated with these regimens. - Determine whether epidermal growth factor receptor and cyclo-oxygenase-2 expressions are independent prognostic markers in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor site (larynx vs other), nodal stage (N0 vs N1 or N2a or N2b vs N2c or N3), and Zubrod performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients undergo standard fractionation radiotherapy 5 days a week for 7 weeks. Patients also receive cisplatin IV on days 1, 22, and 43. - Arm II: Patients undergo accelerated fractionation radiotherapy 5 days a week for 3.5 weeks and then twice a day, 5 days a week, for 2.5 weeks. Patients also receive cisplatin IV on days 1 and 22. Patients with biopsy-proven relapsed disease more than 3 months after completion of therapy undergo surgical resection of the primary tumor. Quality of life is assessed at baseline, during one of the last 2 weeks of treatment, at 3 and 12 months, and then annually for 4 years. Patients are followed at 6-8 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 720 patients (360 per treatment arm) will be accrued for this study within 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 743
• Est. completion date: May 20, 2022
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
• Stage III or IV (T2, N2-3, M0 or T3-4, any N, M0)
• No metastases below the clavicle or more distant by clinical exam or radiology PATIENT CHARACTERISTICS: Age
• 18 and over Performance status
• Zubrod 0-1 Life expectancy
• Not specified Hematopoietic
• Absolute granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3 Hepatic
• Bilirubin no greater than 1.5 mg/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) no greater than 2 times upper limit of normal Renal
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 50 mL/min
• Calcium normal Cardiovascular
• No symptomatic coronary artery disease (angina)
• No myocardial infarction within the past 6 months Other
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• No simultaneous primary tumors
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy
• Not specified Chemotherapy
• No prior chemotherapy Endocrine therapy
• Not specified Radiotherapy
• No prior radiotherapy to the head and neck except radioactive iodine therapy Surgery
• No prior surgery to the primary tumor or nodes except diagnostic biopsy or nodal sampling of neck disease
• No radical or modified neck dissection

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin
100 mg/m^2 intravenously on days 1, 22

Radiation:
• Standard fractionation RT
Radiation will be delivered in 2 Gy per fraction, five fractions a week. The primary tumor and clinically/radiologically involved nodes will receive 70 Gy in 7 weeks and uninvolved nodes will receive 50 Gy in 5 weeks. The anterior lower neck field will be treated with 2 Gy per fraction at 3-cm depth to a total dose of 50 Gy.
• Accelerated fractionation radiation therapy
Radiation to the initial target volume encompassing the gross and subclinical disease sites will be delivered in 1.8 Gy per fraction, five fractions a week to 54 Gy in 30 fractions over 6 weeks. At 32.4 Gy/18 Fx (i.e., latter part of week 4), the boost volume covering gross tumor and clinically/radiologically involved nodes will receive boost irradiation of 1.5 Gy/Fx as second daily fraction (at least 6 h interval) for a total of 12 treatment days (18 Gy total). The primary tumor and clinically/radiologically involved nodes will receive 72 Gy in 42 fractions over 6 weeks and uninvolved nodes will receive 54 Gy in 6 weeks. Clinically/radiologically negative posterior neck should receive a minimum dose of 50.4 Gy at 3 cm. The anterior lower neck field will be treated with 1.8 Gy per fraction at 3-cm depth to a total dose of 50.4 Gy in 28 fractions in 5.6 weeks.

Procedure:
• Conventional surgery for select patients
Surgical removal (salvage resection) of the primary tumor should be performed if biopsy-proven cancer remains more than three months after completion of therapy. The nature of the surgical resection should be dictated by the extent of tumor at the initial evaluation. The operation should be conducted using accepted criteria for primary surgical treatment of the cancer. A planned neck dissection for patients with multiple neck nodes or with lymph nodes exceeding 3 cm in diameter (N2a, N2b, N3) is mandatory, regardless of the clinical and/or radiographic response. A neck dissection is required for patients with N1 disease if a palpable or worrisome radiographic abnormality persists in the neck six weeks after completion of therapy. Surgery should be performed within 2 weeks once the decision for neck dissection is made.

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Akron City Hospital at Summa Health System	Akron	Ohio
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Harrington Cancer Center	Amarillo	Texas
United States	Rose Ramer Cancer Clinic at Anderson Area Medical Center	Anderson	South Carolina
United States	St. John's Cancer Center at St. John's Medical Center	Anderson	Indiana
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Randolph Hospital	Asheboro	North Carolina
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Baton Rouge General Regional Cancer Center	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	St. Francis Hospital and Health Centers	Beech Grove	Indiana
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Cancer Treatment Center at the Medical Center - Bowling Green	Bowling Green	Kentucky
United States	New York Methodist Hospital	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Cancer Institute of New Jersey at the Cooper University Hospital	Camden	New Jersey
United States	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio
United States	Cancer Institute of Cape Girardeau	Cape Girardeau	Missouri
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	John B. Amos Community Cancer Center	Columbus	Georgia
United States	Danville Regional Medical Center	Danville	Virginia
United States	CCOP - Dayton	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Care Center at Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa
United States	John Smith, Jr./Dalton McMichael Cancer Center at Morehead Memorial Hospital	Eden	North Carolina
United States	Alexian Brothers Cancer Care Center	Elk Grove Village	Illinois
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital Cancer Center at Union Hospital	Elkton	Maryland
United States	Hudner Oncology Center at Saint Anne's Hospital	Fall River	Massachusetts
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	21st Century Oncology - Fort Myers	Fort Myers	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Shands Cancer Center at the University of Florida - Jacksonville	Gainesville	Florida
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center	Green Bay	Wisconsin
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Saint Rose Hospital	Hayward	California
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital	Inglewood	California
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	University of Florida Shands Cancer Center	Jacksonville	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Rappahannock General Hospital	Kilmarnock	Virginia
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	St. Rita's Medical Center	Lima	Ohio
United States	Valley Memorial Hospital	Livermore	California
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Medical Center	Manitowoc	Wisconsin
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Middletown Regional Hospital	Middletown	Ohio
United States	South Jersey Healthcare Regional Cancer Center	Millville	New Jersey
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	St. Mary's Cancer Center at Columbia St. Mary's Hospital - Milwaukee Campus	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Providence Holy Cross Cancer Center	Mission Hills	California
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Fox Chase Virtua Health Cancer Program - Marlton	Mount Holly	New Jersey
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Cancer Center at Medical Center of Louisiana - New Orleans	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Summit Medical Center	Oakland	California
United States	Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska
United States	Gulf Coast Cancer Treatment Center	Panama City	Florida
United States	Cancer Center at Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Foundation for Cancer Research and Education	Phoenix	Arizona
United States	Mercy Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York
United States	Saint Joseph Regional Medical Center - Plymouth Campus	Plymouth	Indiana
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	South Suburban Oncology Center	Quincy	Massachusetts
United States	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Annie Penn Cancer Center	Reidsville	North Carolina
United States	Washoe Cancer Services at Washoe Medical Center - Reno	Reno	Nevada
United States	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Radiological Associates of Sacramento Medical Group, Inc.	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center	Saint George	Utah
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Naval Medical Center - San Diego	San Diego	California
United States	J.C. Robinson, M.D. Regional Cancer Center	San Pablo	California
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona
United States	Scottsdale Healthcare - Shea	Scottsdale	Arizona
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn	Scottsdale	Arizona
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Community Memorial Health Center	South Hill	Virginia
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Community Medical Center	Toms River	New Jersey
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	LaFortune Cancer Center at St. John Health System	Tulsa	Oklahoma
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	St. John Macomb Hospital	Warren	Michigan
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	St. Francis Hospital	Wilmington	Delaware
United States	Wilson Medical Center	Wilson	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center	Yakima	Washington
United States	Washington Hematology - Oncology Specialists	Yakima	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

References & Publications (6)

Ang K, Pajak T, Rosenthal DI, et al.: A phase III trial to compare standard versus accelerated fractionation in combination with concurrent cisplatin for head and neck carcinomas (RTOG 0129): report of compliance and toxicity. [Abstract] Int J Radiat Onco

Ang K, Zhang Q, Wheeler RH, et al.: A phase III trial (RTOG 0129) of two radiation-cisplatin regimens for head and neck carcinomas (HNC): impact of radiation and cisplatin intensity on outcome. [Abstract] J Clin Oncol 28 (Suppl 15): A-5507, 2010.

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 J — View Citation

Gillison ML, Harris J, Westra W, et al.: Survival outcomes by tumor human papillomavirus (HPV) status in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129. [Abstract] J Clin Oncol 27 (Suppl 15): A-6003, 2009.

Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012 Jun 10;30(17):2102-11. doi: 10.1200/JCO.2011.38.4099. Epub 2012 May 7. — View Citation

Wuthrick EJ, Zhang Q, Machtay M, et al.: The influence of institutional head and neck cancer (HNC) clinical trial accrual on overall survival (OS): An analysis of RTOG 0129. [Abstract] J Clin Oncol 30 (Suppl 15): A-5530, 2012.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (Percentage of Participants Alive)	Overall survival time is defined as time from randomization to the date of death (failure) or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Secondary	Local-regional Failure (Percentage of Participants With Local-regional Failure)	Local-regional failure time is defined as time from randomization to persistent disease in the primary tumor or regional nodes (considered an event at day 1), relapse/progression in either of those sites (considered an event at the time of relapse/progression), death (competing event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Secondary	Local-regional Failure (Alternate Definition) [Percentage of Participants With Local-regional Failure]	Local-regional failure time is defined as time from randomization to relapse/progression in the primary tumor or regional nodes (event), death due to study cancer or unknown causes (event), death due to other causes (competing event), distant metastasis (competing event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Secondary	Disease-free Survival (Percentage of Participants Alive Without Disease)	Disease-free survival time is defined as time from randomization to persistent disease in the primary tumor or regional nodes (considered an event at day 1), relapse/progression in either of those sites (considered an event at the time of relapse/progression), distant metastasis (event), second primary tumor (event), death (event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Secondary	Progression-free Survival (Alternate Definition of Disease-free Survival) [Percentage of Participants Alive Without Progression]	Progression-free survival time is defined as time from randomization to relapse/progression in the primary site or regional nodes (event), distant metastasis (event), death (event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Secondary	Percentage of Participants With Toxicity Grade 3 or Higher	Acute radiation therapy toxicities (within 90 days from start of radiation therapy) and systemic effects at any time were scored using Common Toxicity Criteria (CTC) version 2.0. Late RT toxicities (> 90 days from start of radiation therapy) were scored by the Radiation Therapy Oncology Group (RTOG)/European Organisation for. Research and Treatment of Cancer (EORTC) criteria. Both criteria grades toxicity severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event/toxicity data.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Performance Status Scale for Head and Neck Cancer (PSS-HN) Normalcy of Diet Score - Area Under the Curve (AUC) at One Year	The PSS-HN is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet (this outcome measure), Public Eating, and Understandability of Speech. Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pre-treatment) and one year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
Secondary	PSS-HN Public Eating Score - AUC at One Year	The Performance Status Scale for Head and Neck Cancer (PSS-HN) is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet , Public Eating (this outcome measure), and Understandability of Speech. Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pretreatment) and one year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
Secondary	PSS-HN Understandability of Speech Score - AUC at One Year	The Performance Status Scale for Head and Neck Cancer (PSS-HN) is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet , Public Eating, and Understandability of Speech (this outcome measure). Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pretreatment) and one year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
Secondary	Head and Neck Radiotherapy Questionnaire (HNRQ) - AUC at One Year	The HNRQ is a patient-reported questionnaire administrated through a paper format; it measures radiation-related side effects and the overall well-being of head and neck cancer patients in the past week. The overall score is the mean of the 22 questions, with a range of 1 to 7. Higher scores indicate better quality of life. Treatment effect was analyzed as time-weighted average between baseline (pre-treatment) and 1 year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
Secondary	Correlation of Epidermal Growth Factor Receptor(EGFR) With Outcomes		From randomization to date of death or last follow-up
Secondary	Correlation of COX-2 With Outcomes		From randomization to date of death or last follow-up