High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

• ClinicalTrials.gov Identifier: NCT00533949
• Recruitment Status: Completed
• First Posted: September 24, 2007
• Results First Posted: May 5, 2017
• Last Update Posted: June 21, 2022
• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); North Central Cancer Treatment Group; Cancer and Leukemia Group B; NRG Oncology
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Study Description

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Radiation Toxicity	Biological: Cetuximab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: 60 Gy RT; Radiation: 74 Gy RT	Phase 3

Detailed Description:

OBJECTIVES:

Primary

• To compare the overall survival of patients with newly diagnosed, unresectable stage IIIA or IIIB non-small cell lung cancer treated with high- versus standard-dose conformal radiotherapy with concurrent and consolidation chemotherapy comprising carboplatin and paclitaxel.
• To compare the overall survival of patients treated with versus without cetuximab in the setting of concurrent chemotherapy

Secondary

• To compare progression-free survival and local-regional tumor control in patients treated with these regimens.
• To compare the toxicity of high- versus standard-dose conformal radiotherapy and concurrent chemotherapy with versus without cetuximab in these patients.
• To investigate the prognostic and predictive effects of gross tumor volume on overall survival of patients treated with these regimens.
• To compare the quality of life of patients treated with these regimens.
• To correlate outcomes (i.e., survival, toxicity, or QOL) in these patients with biological parameters.
• To analyze the predictive value of pre-treatment standardized uptake value (SUV) of positron emission tomography (PET) scan in predicting survival, distant metastasis, and local-regional control in patients treated with these regimens.
• To explore biological markers to predict clinical outcome including survival, distant metastasis, local-regional control, and QOL (including toxicity) in patients treated with these regimens.
• To prospectively collect and bank tissue, blood, and urine specimens for future biomarker analyses in predicting clinical outcome in patients treated with these regimens.
• To investigate associations between epidermal growth factor receptor (EGFR) expression and toxicity, response, overall survival, and progression-free survival.

OUTLINE: This is a multicenter study. Patients are stratified according to PET staging (yes vs no), radiotherapy technique (3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy), Zubrod performance status (0 vs 1), and histology (squamous vs non-squamous). Patients are randomized to 1 of 4 treatment arms. (Arms II and IV closed to accrual effective 6/17/11)

Patients may undergo tumor tissue, blood, and urine collection periodically during study for tissue banking or biomarker correlative studies.

Patients may undergo quality-of-life assessment at baseline and periodically during study.

After completion of study therapy, patients are followed periodically for 5 years and then annually thereafter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 544 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This study was revised 06/18/08 to a 2x2 factorial design to evaluate the addition of cetuximab to the radiation therapy regimens.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy With Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients With Stage IIIA/IIIB Non-Small Cell Lung Cancer
• Study Start Date: November 2007
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 60 Gy RT; 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin	Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Name: Paraplatin; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Abraxane; Radiation: 60 Gy RT; Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks.; Other Name: RT
Experimental: 74 Gy RT; 74 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin	Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Name: Paraplatin; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Abraxane; Radiation: 74 Gy RT; Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7.5 weeks.
Experimental: 60 Gy RT + Cetuximab; 60 Gy Radiation therapy with concurrent cetuximab, paclitaxel, and carboplatin followed by consolidation cetuximab, paclitaxel, and carboplatin	Biological: Cetuximab; Loading dose: 400 mg/m2, IV, one week prior to start of radiation therapy (RT). Then, beginning day 1 of RT, 250 mg/m2, IV, weekly; for 60 Gy arm for 15 weeks, for 74 Gy arm for 16 weeks.; Other Name: Erbitux; Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Name: Paraplatin; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Abraxane; Radiation: 60 Gy RT; Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks.; Other Name: RT
Experimental: 74 Gy RT + Cetuximab; 74 Gy Radiation therapy with concurrent cetuximab, paclitaxel, and carboplatin followed by consolidation cetuximab, paclitaxel, and carboplatin	Biological: Cetuximab; Loading dose: 400 mg/m2, IV, one week prior to start of radiation therapy (RT). Then, beginning day 1 of RT, 250 mg/m2, IV, weekly; for 60 Gy arm for 15 weeks, for 74 Gy arm for 16 weeks.; Other Name: Erbitux; Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Name: Paraplatin; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Abraxane; Radiation: 74 Gy RT; Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7.5 weeks.

Outcome Measures

Primary Outcome Measures :

1. Overall Survival [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
   Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

Secondary Outcome Measures :

1. Progression-free Survival [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
   A failure for progression-free survival (PFS) is the first occurrence of local or regional progression, distant metastases, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Time is measured from the date of randomization to the date of first failure. Patients without failure are censored at the date of last follow-up.
2. Local-regional Failure (Reported as Two-year Estimates) [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
   A failure for local-regional failure is the first occurrence of local or regional progression. Time is measured from the date of randomization to the date of first failure. Patients alive without local or regional failure at the time of last follow-up are censored. Patients who died without local or regional failure are considered as having competing risk at the time of death. Local-regional failure was estimated by the cumulative incidence method and 2 year estimates are reported.
3. Percentage of Participants With Grade 3-5 Esophagitis and Pneumonitis Adverse Events as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
   Treatment-related esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.
4. Percentage of Participants With Other Grade 3-5 Adverse Events as Assessed by NCI CTCAE v3.0 [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
   Treatment-related adverse events other than esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.
5. Death During or Within 30 Days of Discontinuation of Protocol Treatment [ Time Frame: From start of protocol treatment to 24 months. ]
   Deaths regardless of cause and occuring during or within 30 days of discontinuation of protocol treatment were evaluated.
6. Percentage of Patients With Decline From Baseline to 3 Months in the Lung Cancer Subscale (LCS) of the Functional Assessment of the Cancer Therapy Trial Outcome Index (FACT-TOI). [ Time Frame: At baseline and 3 months. ]
   A decline of 2 points in the LCS from baseline to 3 months was considered a clinically meaningful change indicating a decline in quality of life. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.
7. Patient-reported Swallowing Score (Area Under the Curve) [ Time Frame: From randomization to 6 weeks after start of radiation therapy (6-10 weeks from randomization) ]
   Patients completed a swallowing diary prior to the start of treatment and then daily during treatment. Patients recorded a score to indicate problems with swallowing on that day (1-None, 2-Mild soreness only, 3-Can swallow solids with some difficulty, 4-Cannot swallow solids, 5-Cannot swallow liquids). These scores were then plotted across time and the area under the curve from baseline until the end of week 6 was calculated. A lower area under the curve indicates better swallowing ability. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.
8. EuroQoL (EQ5D) Visual Analog Scale (VAS) Through One Year (Area Under the Curve) [ Time Frame: From randomization to one year ]
   The visual analogue scale is a self-assessment of current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The area under the curve of each subject's EQ5D visual analog scale (VAS) response trajectory within 1 year was calculated. The EQ5D VAS utility was normalized by the baseline score. The trajectory included all available time points through one year. If a subject died within one year, the EQ5D VAS was reduced to 0 at the time of death. If subject was censored within one year, the EQ5D utility curve was truncated at the time of censoring. The scores were plotted across time and the area under the curve was calculated. A greater area under the curve indicates a better health state. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation
9. Overall Survival and Local-regional Failure by Epithelial Growth Factor Receptor (EGFR) Group [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
   EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells. EGFR H-Score is a measure of staining intensity ranging from 0 to 300 where a higher value indicates greater intensity of EGFR. Available tumor samples were evaluated for EGFR and given an H-Score. Patients were divided into two groups based on H-Score values dichotomized at 200. All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method. A local-regional event is the first development of progressive disease locally or regionally, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are reported.
10. Percentage of Patients With Grade 3+ Adverse Events by Epithelial Growth Factor Receptor (EGFR) Group [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
    EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells. EGFR H-Score is a measure of staining intensity ranging from 0 to 300 where a higher value indicates greater intensity of EGFR. Available tumor samples were evaluated for EGFR and given an H-Score. Patients were divided into two groups based on H-Score values dichotomized at 200. Worst toxicity as determined by adverse events was used as a measure of a patient's quality of life (QOL). Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Highest grade (worst) adverse event (AE) per subject was counted.
11. Prognostic and Predictive Effects of Gross Tumor Volume (GTV) on Overall Survival [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
    Gross tumor volume (GTV) is defined as the combined volume (cubic centimeters) of the primary tumor and clinically positive lymph nodes seen either on the planning computed tomography (CT) scan or the pretreatment positron emission tomography (PET) scan. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. GTV was evaluated as a continuous variable therefore overall survival time is not summarized by GTV. "Prognostic" refers to the main effect and "predictive" refers to the interaction between GTV and treatment arm.
12. Prognostic Value of Pre-treatment Standardized Uptake Value (SUV) of Positron Emission Tomography (PET) Scan in Predicting Survival, Distant Metastasis, and Local-regional Failure [ Time Frame: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months. ]
    Standardized uptake value (SUV) is a simple way of determining activity in PET imaging. It is a mathematically derived ratio of tissue radioactivity concentration at a point in time and the injected dose of radioactivity per kilogram of the patient's body weight. All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method. Local-regional and distant metastasis events are the first development of progressive disease locally/regionally or distant metastasis, respectively, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are presented. PET SUV was evaluated as a continuous variable therefore the outcome variables are not summarized by PET SUV.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

1. Pathologically proven (either histologic or cytologic) diagnosis of Stage IIIA or IIIB non-small cell lung cancer (NSCLC); excluding patients with N3 disease based on supraclavicular or contralateral hilar adenopathy, [according to American Joint Committee on Cancer (AJCC) Staging, 6th edition; see appendix III] within 12 weeks of registration; patients who present with N2 or N3 disease and an undetectable NSCLC primary tumor also are eligible.

2. Patients must be considered unresectable or inoperable; Note: Patients who have had a nodal recurrence after surgery for an early-stage NSCLC are eligible if the following criteria are met:

   • Nodal recurrence must be N1 or N2; N3 is not eligible.
   • The initial primary must have been staged as T1-2, N0, M0.
   • The node must be biopsied within 12 weeks of registration.
   • The node must be measurable.
   • The patient must not have received prior chemotherapy or radiation for this lung cancer.
   • Prior curative surgery must have been at least 6 months prior to the nodal recurrence.
   • The exception to a prior invasive malignancy does not apply to the initial lung primary.

3. Stage III A or B disease, including no distant metastases, based upon the following minimum diagnostic workup are acceptable:

   • History/physical examination, including documentation of height, weight, body surface area (BSA), and vital signs within 8 weeks prior to registration;
   • Computed tomographic (CT)/Magnetic Resonance Imaging (MRI) imaging of the lung and upper abdomen through the adrenal glands within 6 weeks prior to registration;
   • An MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 6 weeks prior to registration; Note: The use of intravenous contrast is required for the MRI or CT. An MRI without contrast is only permitted if the patient has a contrast allergy.
   • Whole-body fluorodeoxyglucose (FDG) - Positron Emission Tomography(PET) or PET/CT or if no PET is available, a bone scan is required within 6 weeks prior to registration; Note: If a PET is done that shows clear adrenals and lungs, then a CT scan of chest only is permitted.

4. If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (incurable T4 disease):

   • When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
   • Exudative pleural effusions are excluded, regardless of cytology;
   • Effusions that are minimal (i.e. not visible on chest x-ray) that are too small to safely tap are eligible.
5. Patients must have measurable or evaluable disease.
6. Patients with post-obstructive pneumonia are eligible.
7. Patients must be at least 3 weeks from prior thoracotomy (if performed).
8. Zubrod Performance Status 0-1;
9. Age ≥ 18;
10. Pulmonary function tests (PFTs) including forced expiratory volume in one second (FEV1) within 12 weeks prior to registration; for FEV1, the best value obtained pre- or post bronchodilator must be ≥ 1.2 liters/second or ≥ 50% predicted.

11. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows:

    • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
    • Platelets ≥ 100,000 cells/mm3;
    • Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.)
12. Serum creatinine within normal institutional limits or creatinine clearance ≥60 ml/min;
13. Bilirubin must be within or below normal institutional limits;
14. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2.5 x the institutional upper limit of normal (IULN);
15. Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria:

1. N3 supraclavicular disease;
2. Greater than minimal, exudative, or cytologically positive pleural effusions;
3. Involved contralateral hilar nodes (i.e. greater than 1.5 cm on short axis or positive on PET scan);
4. ≥ 10% weight loss within the past month;
5. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.
6. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable.
7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
8. Prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway;
9. Prior severe infusion reaction to a monoclonal antibody;

10. Severe, active co-morbidity, defined as follows:

    • Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
    • Transmural myocardial infarction within the last 6 months;
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
    • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    • Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
11. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
12. Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin;
13. Uncontrolled neuropathy grade 2 or greater regardless of cause.

Contacts and Locations

Locations

United States, Alabama

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States, 35294

United States, Arizona

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States, 85259-5499

Arizona Oncology - Tucson

Tucson, Arizona, United States, 85704

United States, California

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, United States, 95608

Enloe Cancer Center at Enloe Medical Center

Chico, California, United States, 95926

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, United States, 94524-4110

Saint Agnes Cancer Center at Saint Agnes Medical Center

Fresno, California, United States, 93720

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States, 92093-0658

Memorial Medical Center

Modesto, California, United States, 95355

St. Joseph Hospital Regional Cancer Center - Orange

Orange, California, United States, 92868

Feather River Hospital Cancer Center

Paradise, California, United States, 95969

Radiation Oncology Center - Roseville

Roseville, California, United States, 95661

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, United States, 95815

University of California Davis Cancer Center

Sacramento, California, United States, 95817

Saint Helena Hospital

Saint Helena, California, United States, 94574

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94115

Stanford Cancer Center

Stanford, California, United States, 94305-5824

United States, Colorado

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, United States, 80933

Swedish Medical Center

Englewood, Colorado, United States, 80110

Poudre Valley Radiation Oncology

Fort Collins, Colorado, United States, 80528

North Suburban Medical Center

Thornton, Colorado, United States, 80229

United States, Delaware

CCOP - Christiana Care Health Services

Newark, Delaware, United States, 19713

United States, District of Columbia

Washington Cancer Institute at Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

Broward General Medical Center Cancer Center

Fort Lauderdale, Florida, United States, 33316

University of Florida Shands Cancer Center

Gainesville, Florida, United States, 32610-0232

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, United States, 33021

Integrated Community Oncology Network

Jacksonville Beach, Florida, United States, 32250

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States, 32207

Integrated Community Oncology Network at Southside Cancer Center

Jacksonville, Florida, United States, 32207

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States, 32224

Baptist Medical Center South

Jacksonville, Florida, United States, 32258

Ella Milbank Foshay Cancer Center at Jupiter Medical Center

Jupiter, Florida, United States, 33458

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States, 33140

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States, 33176

Integrated Community Oncology Network - Orange Park

Orange Park, Florida, United States, 32073

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, United States, 32806

Florida Cancer Center - Palatka

Palatka, Florida, United States, 32177

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States, 32504

Flagler Cancer Center

Saint Augustine, Florida, United States, 32086

United States, Georgia

Georgia Cancer Center for Excellence at Grady Memorial Hospital

Atlanta, Georgia, United States, 30303

Emory Crawford Long Hospital

Atlanta, Georgia, United States, 30308

Piedmont Hospital

Atlanta, Georgia, United States, 30309

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States, 30322

Charles B. Eberhart Cancer Center at DeKalb Medical Center

Decatur, Georgia, United States, 30033

United States, Idaho

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

Boise, Idaho, United States, 83706

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States, 83712

United States, Illinois

University of Chicago Cancer Research Center

Chicago, Illinois, United States, 60637-1470

Creticos Cancer Center at Advocate Illinois Masonic Medical Center

Chicago, Illinois, United States, 60657

Community Cancer Center

Normal, Illinois, United States, 61761

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, United States, 61554

Methodist Medical Center of Illinois

Peoria, Illinois, United States, 61636

OSF St. Francis Medical Center

Peoria, Illinois, United States, 61637

United States, Indiana

Radiation Oncology Associates Southwest

Fort Wayne, Indiana, United States, 46804

Parkview Regional Cancer Center at Parkview Health

Fort Wayne, Indiana, United States, 46805

Center for Cancer Care at Goshen General Hospital

Goshen, Indiana, United States, 46526

Central Indiana Cancer Centers - East

Indianapolis, Indiana, United States, 46219

Community Regional Cancer Care at Community Hospital East

Indianapolis, Indiana, United States, 46219

Community Regional Cancer Care at Community Hospital North

Indianapolis, Indiana, United States, 46256

Cancer Center at Ball Memorial Hospital

Muncie, Indiana, United States, 47303-3499

United States, Iowa

Mercy Regional Cancer Center at Mercy Medical Center

Cedar Rapids, Iowa, United States, 52403

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, United States, 50309

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, United States, 50314

Mercy Cancer Center at Mercy Medical Center - North Iowa

Mason City, Iowa, United States, 50401

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States, 51101

United States, Kentucky

Central Baptist Hospital

Lexington, Kentucky, United States, 40503-9985

United States, Louisiana

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, United States, 71315-3198

Mary Bird Perkins Cancer Center - Baton Rouge

Baton Rouge, Louisiana, United States, 70809

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States, 70112

CCOP - Ochsner

New Orleans, Louisiana, United States, 70121

United States, Maryland

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States, 21201

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States, 21229

Shore Regional Cancer Center at Memorial Hospital - Easton

Easton, Maryland, United States, 21601

Peninsula Regional Medical Center

Salisbury, Maryland, United States, 21801

United States, Massachusetts

Baystate Regional Cancer Program at D'Amour Center for Cancer Care

Springfield, Massachusetts, United States, 01107

United States, Michigan

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States, 48106-0995

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201-1379

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States, 48202

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States, 49503

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States, 48236

West Michigan Cancer Center

Kalamazoo, Michigan, United States, 49007-3731

St. Mary Mercy Hospital

Livonia, Michigan, United States, 48154

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, United States, 48060

United States, Minnesota

Fairview Ridges Hospital

Burnsville, Minnesota, United States, 55337

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, United States, 55109

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States, 55407

Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, United States, 55422-2900

Mayo Clinic Cancer Center

Rochester, Minnesota, United States, 55905

CentraCare Clinic - River Campus

Saint Cloud, Minnesota, United States, 56303

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, United States, 55101

United States, Mississippi

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States, 39216

Regional Cancer Center at Singing River Hospital

Pascagoula, Mississippi, United States, 39581

United States, Missouri

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Saint Louis, Missouri, United States, 63110

Barnes-Jewish West County Hospital

Saint Louis, Missouri, United States, 63141

Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters

Saint Peters, Missouri, United States, 63376

United States, Montana

Billings Clinic - Downtown

Billings, Montana, United States, 59107-7000

United States, Nebraska

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, United States, 68848-1990

Saint Elizabeth Cancer Institute at Saint Elizabeth Regional Medical Center

Lincoln, Nebraska, United States, 68510

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States, 68114

United States, Nevada

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States, 89106

Renown Institute for Cancer at Renown Regional Medical Center

Reno, Nevada, United States, 89502

Saint Mary's Regional Medical Center

Reno, Nevada, United States, 89503

United States, New Hampshire

Payson Center for Cancer Care at Concord Hospital

Concord, New Hampshire, United States, 03301

Center for Cancer Care at Exeter Hospital

Exeter, New Hampshire, United States, 03833

Elliot Regional Cancer Center at Elliot Hospital

Manchester, New Hampshire, United States, 03103

United States, New Jersey

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

Marlton, New Jersey, United States, 08053

UMDNJ University Hospital

Newark, New Jersey, United States, 07103

J. Phillip Citta Regional Cancer Center at Community Medical Center

Toms River, New Jersey, United States, 08755

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees, New Jersey, United States, 08043

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131-5636

United States, New York

New York Oncology Hematology, PC at Albany Regional Cancer Care

Albany, New York, United States, 12206

Veterans Affairs Medical Center - Albany

Albany, New York, United States, 12208

Sands Cancer Center

Canandaigua, New York, United States, 14424

St. Luke's - Roosevelt Hospital Center - St.Luke's Division

New York, New York, United States, 10025

Highland Hospital of Rochester

Rochester, New York, United States, 14620

University Radiation Oncology at Parkridge Hospital

Rochester, New York, United States, 14626

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States, 14642

SUNY Upstate Medical University Hospital

Syracuse, New York, United States, 13210

United States, North Carolina

Alamance Cancer Center at Alamance Regional Medical Center

Burlington, North Carolina, United States, 27216

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States, 27599-7295

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States, 28232-2861

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States, 28233-3549

Kinston Medical Specialists

Kinston, North Carolina, United States, 28501

FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center

Pinehurst, North Carolina, United States, 28374

Cancer Centers of North Carolina - Raleigh

Raleigh, North Carolina, United States, 27607

United States, North Dakota

CCOP - MeritCare Hospital

Fargo, North Dakota, United States, 58122

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, United States, 58201

Trinity CancerCare Center

Minot, North Dakota, United States, 58701

United States, Ohio

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, United States, 44307

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States, 44309-2090

Barberton Citizens Hospital

Barberton, Ohio, United States, 44203

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, United States, 44710-1799

Adena Regional Medical Center

Chillicothe, Ohio, United States, 45601

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States, 45267

Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44106-5065

Cleveland Clinic Cancer Center at Fairview Hospital

Cleveland, Ohio, United States, 44111

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States, 44195

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, United States, 43214-3998

Cleveland Clinic Cancer Center

Independence, Ohio, United States, 44131

Hillcrest Cancer Center at Hillcrest Hospital

Mayfield Heights, Ohio, United States, 44124

Southwest General Health Center

Middleburg Heights, Ohio, United States, 44130

UHHS Chagrin Highlands Medical Center

Orange Village, Ohio, United States, 44122

St. Charles Mercy Hospital

Oregon, Ohio, United States, 43616

North Coast Cancer Care, Incorporated

Sandusky, Ohio, United States, 44870

Flower Hospital Cancer Center

Sylvania, Ohio, United States, 43560

St. Anne Mercy Hospital

Toledo, Ohio, United States, 43623

UHHS Westlake Medical Center

Westlake, Ohio, United States, 44145

Cleveland Clinic - Wooster

Wooster, Ohio, United States, 44691

United States, Oklahoma

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States, 73104

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, United States, 74136

United States, Oregon

Willamette Valley Cancer Center - Eugene

Eugene, Oregon, United States, 97401

United States, Pennsylvania

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, United States, 18105

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States, 19010

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States, 17822-0001

Northeast Radiation Oncology Center

Dunmore, Pennsylvania, United States, 18512

Dale and Frances Hughes Cancer Center at Pocono Medical Center

East Stroudsburg, Pennsylvania, United States, 18301

Regional Cancer Center - Erie

Erie, Pennsylvania, United States, 16505

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033-0850

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, United States, 19301-1792

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States, 19107-5541

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States, 19111-2497

Frankford Hospital Cancer Center - Torresdale Campus

Philadelphia, Pennsylvania, United States, 19114

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States, 19141

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

Reading, Pennsylvania, United States, 19612-6052

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, United States, 18711

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States, 19096

United States, South Carolina

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Cancer Centers of the Carolinas - Faris Road

Greenville, South Carolina, United States, 29605

CCOP - Greenville

Greenville, South Carolina, United States, 29615

Cancer Centers of the Carolinas - Seneca

Seneca, South Carolina, United States, 29672

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States, 29303

United States, South Dakota

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States, 57117-5039

United States, Tennessee

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

Kingsport, Tennessee, United States, 37662

United States, Texas

Harrington Cancer Center

Amarillo, Texas, United States, 79106

Texas Oncology, PA at Texas Cancer Center - Arlington South

Arlington, Texas, United States, 76014

Texas Oncology, PA at Harris Center HEB

Bedford, Texas, United States, 76022

Texas Oncology, PA at Texas Cancer Center - Denton South

Denton, Texas, United States, 76210

Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital

Fort Worth, Texas, United States, 76104

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States, 77030-4009

Longview Cancer Center

Longview, Texas, United States, 75601

West Texas Cancer Center

Odessa, Texas, United States, 79761

Cancer Care Centers of South Texas - Northeast

San Antonio, Texas, United States, 78217

Texas Oncology, PA at Texas Cancer Center - Sherman

Sherman, Texas, United States, 75090

Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land

Sugar Land, Texas, United States, 77479

Tyler Cancer Center

Tyler, Texas, United States, 75702

United States, Utah

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States, 84157

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States, 84604

Dixie Regional Medical Center - East Campus

Saint George, Utah, United States, 84770

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, United States, 84106

United States, Vermont

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States, 05401

United States, Virginia

University of Virginia Cancer Center

Charlottesville, Virginia, United States, 22908

United States, Washington

CCOP - Virginia Mason Research Center

Seattle, Washington, United States, 98101

Cancer Care Northwest - Spokane South

Spokane, Washington, United States, 99202

United States, Wisconsin

Theda Care Cancer Institute

Appleton, Wisconsin, United States, 54911

Midelfort Clinic - Luther

Eau Claire, Wisconsin, United States, 54703-1510

Luther Midlelfort Hospital

Eau Claire, Wisconsin, United States, 54703

Bellin Memorial Hospital

Green Bay, Wisconsin, United States, 54301

St. Mary's Hospital Medical Center - Green Bay

Green Bay, Wisconsin, United States, 54303

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States, 54307-3508

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, United States, 54601

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, United States, 54143

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States, 53226

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, United States, 53295

D.N. Greenwald Center

Mukwonago, Wisconsin, United States, 53149

All Saints Cancer Center at Wheaton Franciscan Healthcare

Racine, Wisconsin, United States, 53405

Door County Cancer Center at Door County Memorial Hospital

Sturgeon Bay, Wisconsin, United States, 54235-1495

Waukesha Memorial Hospital Regional Cancer Center

Waukesha, Wisconsin, United States, 53188

Riverview UW Cancer Center at Riverview Hospital

Wisconsin Rapids, Wisconsin, United States, 54494

Canada, Alberta

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada, T2N 4N2

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Ontario

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada, H2L 4M1

Canada, Saskatchewan

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, Canada, S4T 7T1

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada, S7N 4H4

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

North Central Cancer Treatment Group

Cancer and Leukemia Group B

NRG Oncology

Investigators

• Principal Investigator: Jeffrey Bradley, MD; Mallinckrodt Institute of Radiology at Washington University Medical Center
• Study Chair: Hak Choy, MD; Simmons Cancer Center
• Study Chair: Gregory A. Masters, MD; CCOP - Christiana Care Health Services
• Study Chair: Steven E. Schild, MD; Mayo Clinic
• Study Chair: Alex A. Adjei, MD, PhD; Roswell Park Cancer Institute
• Study Chair: Jeffrey A. Bogart, MD; State University of New York - Upstate Medical University
• Study Chair: Arthur William Blackstock, MD; Wake Forest University Health Sciences
• Study Chair: Mark A. Socinski, MD; UNC Lineberger Comprehensive Cancer Center
• Study Chair: George Blumenschein, MD; M.D. Anderson Cancer Center
• Study Chair: Ritsuko Komaki, MD; M.D. Anderson Cancer Center
• Study Chair: Jeff Sloan, PhD, HSR; Mayo Clinic
• Study Chair: Mark Dobelbower, MD PhD; University of Alabama Medical Center
• Study Chair: Tien Hoang, MD; University of Wisconsin, Madison
• Study Chair: Ken Forster, PhD; H. Lee Moffitt Cancer Center
• Study Chair: Benjamin Movsas, MD; Henry Ford Hospital
• Study Chair: Joe Y. Chang, MD PhD; M.D. Anderson Cancer Center
• Study Chair: Joseph O. Deasy, PhD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive. 

Publications of Results:

Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. doi: 10.1200/JCO.19.01162. Epub 2019 Dec 16.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Movsas B, Hu C, Sloan J, Bradley J, Komaki R, Masters G, Kavadi V, Narayan S, Michalski J, Johnson DW, Koprowski C, Curran WJ Jr, Garces YI, Gaur R, Wynn RB, Schallenkamp J, Gelblum DY, MacRae RM, Paulus R, Choy H. Quality of Life Analysis of a Radiation Dose-Escalation Study of Patients With Non-Small-Cell Lung Cancer: A Secondary Analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial. JAMA Oncol. 2016 Mar;2(3):359-67. doi: 10.1001/jamaoncol.2015.3969.

Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. doi: 10.1016/S1470-2045(14)71207-0. Epub 2015 Jan 16.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00533949
• Other Study ID Numbers: RTOG 0617; CDR0000564240; NCCTG-N0628; CALGB-30609; NCI-2013-01762 ( Registry Identifier: CTRP (Clinical Trials Reporting Program) )
• First Posted: September 24, 2007
• Results First Posted: May 5, 2017
• Last Update Posted: June 21, 2022
• Last Verified: May 2022

Keywords provided by Radiation Therapy Oncology Group:

radiation toxicity; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Paclitaxel; Carboplatin; Cetuximab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological