Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer

Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer

A Phase I Study of Gemcitabine, Carboplatin or Gemcitabine, Paclitaxel and Radiation Therapy Followed by Adjuvant Chemotherapy for Patients With Favorable Prognosis Inoperable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, carboplatin, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining combination chemotherapy with radiation therapy in treating patients who have stage IIIA or stage IIIB non-small cell lung cancer.

OBJECTIVES: Determine the maximum tolerated dose (MTD) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage IIIA or IIIB non-small cell lung cancer. Determine the MTD of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients. OUTLINE: This is a multicenter, dose-escalation study of gemcitabine and paclitaxel. Patients are sequentially assigned to 1 of 3 treatment regimens. Regimen A: Patients receive gemcitabine IV over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1. Regimen B (closed to accrual as of 5/13/03): Patients receive gemcitabine and thoracic radiotherapy as in regimen A and carboplatin IV over 30 minutes on days 1, 8, 22, 29, and 43. Regimen C: Patients receive gemcitabine and thoracic radiotherapy as in regimen A and paclitaxel IV over 1 hour on days 1, 8, 22, 29, and 43. At 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine IV over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin IV over 30 minutes on days 71 and 92. The first 6 patients enrolled receive regimen A to determine the safety of the initial dose of gemcitabine. After completion of regimen A, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen B (closed to accrual as of 5/13/03) until the maximum tolerated dose (MTD) is determined. In a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen C until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity. Patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 29 months.

To determine the maximum tolerated dose of gemcitabine with carboplatin-based chemotherapy and radiation therapy

To determine the maximum tolerated dose of gemcitabine with paclitaxel-based chemotherapy and radiation therapy

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria: Medically inoperable stage IIIA Unresectable stage IIIA or IIIB Measurable disease on three-dimensional planning CT scan No post-resection intrathoracic tumor recurrence No pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure No evidence of small cell histology No evidence of hematogenous or distant metastases PATIENT CHARACTERISTICS: Age: Not specified Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Platelet count at least 100,000/mm^3 Absolute granulocyte count at least 2,000/mm^3 Hemoglobin at least 8.0 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL Serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease) Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No myocardial infarction within the past 6 months No symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia Pulmonary: Forced expiratory volume (FEV)_1 greater than 1,000 mL Other: No other invasive malignancy within the past 3 years except nonmelanoma skin cancer No weight loss of more than 10% in 3 months prior to diagnosis 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 thoracic or neck radiotherapy Surgery: See Disease Characteristics No prior complete or subtotal tumor resection

Choy H, Jain AK, Moughan J, Curran W, Whipple G, Demas WF, Ettinger DS. RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by adjuvant chemotherapy for patients with favorable prognosis inoperable stage IIIA/B non-small cell lung cancer. J Thorac Oncol. 2009 Jan;4(1):80-6. doi: 10.1097/JTO.0b013e318191503f.

Choy H, Swann S, Curran W, et al.: A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: an RTOG 0017 study. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-70, S42, 2005.

Choy H, Swann S, Walter C, et al.: A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: an RTOG study. [Abstract] J Clin Oncol 23 (Suppl 16): A-7103, 646s, 2005.