Cisplatin, Pemetrexed Disodium, and Radiation Therapy Followed by Docetaxel in Treating Patients With Stage III Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Assess 1-year survival of stage III non-small cell lung cancer (NSCLC) patients treated with cisplatin, pemetrexed disodium, and concurrent thoracic radiotherapy followed by consolidation therapy with docetaxel.

Secondary

• Assess the progression-free survival and overall survival.
• Assess the toxicity of this regimen.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over 60 minute on day 1. Treatment repeats every 21 days for 3 courses in the absence of unacceptable toxicity. Patients also receive concurrent thoracic radiotherapy in weeks 1-7. Between 3-8 weeks after completion of chemoradiotherapy, patients with no progressive disease receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for 3 courses.

After completion of study therapy, patients are followed at 1 month and periodically thereafter.

PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria:

• Stage IIIA disease, meeting all of the following criteria:

• Mediastinal lymph node involvement

• Greater than one mediastinal lymph node enlarged on CT scan, confirmed by positron emission tomography (PET) scan
• Paralyzed left vocal cord with separate lung primary distinct from the aorto-pulmonary lymph nodes on the CT scan
• Stage IIIB disease, meeting all of the following criteria:

• N3 lymph node involvement

• Enlarged N3 lymph nodes on CT scan confirmed by PET scan

• Lymph node involvement may not extend to cervical lymph nodes other than supraclavicular lymph nodes
• Right-sided primary tumor with left vocal cord paralysis
• Evidence of tumor extension into the mediastinum and/or mediastinal structures by mediastinoscopy, bronchoscopy, or CT scan
• No evidence of malignant pleural effusion unless effusion is only evident on CT scan
• No more than 1 parenchymal lesions on the same or opposite sides of the lung
• No brain metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

• SWOG performance status 0 or 1
• Platelet count ≥ 100,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Creatinine clearance ≥ 45 mL/min
• Bilirubin normal
• Transaminases (SGOT and/or SGPT) ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Total lung volume (i.e., right and left lung minus the gross tumor volume) receiving greater than 20 Gy of radiation ≤ 40%
• FEV_1 ≥ 70% of predicted
• DLCO ≥ 50 mL/min
• No other concurrent malignancy

• Prior malignancy allowed provided it is in clinical control and is not likely to impact clinical outcome in the opinion of the treating physician
• No peripheral neuropathy ≥ grade 2
• No serious medical illness, including, but not limited to, any of the following:

• Uncontrolled congestive heart failure
• Uncontrolled angina
• Myocardial infarction
• Cerebrovascular event within the past 6 months
• History of chronic active hepatitis
• History of HIV infection
• Active bacterial infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be willing and able to take folic acid, cyanocobalamin (vitamin B12), or dexamethasone

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for NSCLC
• No concurrent participation in another therapeutic investigational study
• Concurrent ibuprofen (400 mg four times daily) allowed during pemetrexed disodium administration provided the patient has normal renal function
• No concurrent aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) 2 days before, during, and for 2 days after pemetrexed disodium administration

• Patients on long-acting NSAIDs (e.g. naproxen sodium, diflunisal, nabumetone, or celecoxib) must be willing or able to discontinue usage 5 days prior to, during, and for 2 days after pemetrexed disodium administration