Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To evaluate the safety of adding oral soy isoflavone to concurrent chemotherapy and radiotherapy for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC).

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

GROUP I (SQUAMOUS CELL HISTOLOGY): Patients receive etoposide intravenously (IV) over 1 hour on days 1-5 and 29-33, cisplatin IV over 1 hour on days 1, 8, 29, and 36, and undergo radiation therapy (RT) 5 days a week for 6.6 weeks. Within 48 hours of initiating treatment, patients receive soy isoflavones orally (PO) daily on days 1-90.

GROUP II (NON-SQUAMOUS CELL HISTOLOGY): Patients receive pemetrexed disodium IV over 10 minutes on days 1, 22, and 43 and cisplatin IV over 1 hour on days 1, 22, and 43. Patients also undergo RT and receive soy isoflavones as in Group I.

After completion of study treatment, patients are followed up at 4 weeks and then every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

Inclusion criteria

• Histologic or cytologic diagnosis of stage III non-small cell lung cancer; patients will need to meet the following criteria for stage IIIA or IIIB diagnosis:

• IIIA

• Histologic or cytologic diagnosis of ipsilateral mediastinal lymph node involvement, or
• Tumors greater than 7 cm or with chest wall invasion, or involvement of one of the following diaphragm, phrenic nerve, mediastinal pleura or parietal pericardium with hilar or mediastinal lymph node involvement
• More than one mediastinal lymph node enlarged on computed tomography (CT) scan and the same lymph nodes positive on positron emission tomography (PET) scans or
• Paralyzed left vocal cord with separate lung primary distinct from the aorto-pulmonary lymph nodes on the CT scan
• IIIB

• Histologic or cytologic diagnosis of N3 lymph node involvement; or
• Enlarged N3 lymph nodes on CT scan that are positive on PET scan as well; patient must not have extension of lymph node involvement to cervical lymph nodes other than supraclavicular lymph nodes; or
• Right sided primary with left vocal cord paralysis; or
• Evidence of tumor extension into the mediastinum and/or mediastinal structures either at the time of mediastinoscopy, bronchoscopy or on CT scans
• Patients with a nodules in the same lung but no other areas of involvement
• Patients with prior surgically resected stage I NSCLC who did not receive any adjuvant therapy, who now have stage IIIA or B NSCLC will be eligible
• Southwestern Oncology Group (SWOG) performance status 0 or 1
• Absolute neutrophil count of > 1.5 x 10^9/L
• Platelet count > 100,000 x 10^9/L
• Serum creatinine =< 1.5 times the institutional upper limit of normal (ULN)
• Calculated creatinine clearance (Cockcroft-Gault formula) of >= 45mL/min
• Serum bilirubin > ULN
• Transaminases (serum glutamic oxaloacetic transaminase [SGOT] and/or serum glutamate pyruvate transaminase [SGPT]) > 1.5 times institutional ULN
• Alkaline phosphatase >= 2.5 times ULN
• Forced expiratory volume in one second (FEV1) of >= 1 liter and diffusion capacity of carbon monoxide (DLCO) >= 40% of predicted
• Patient should undergo brain imaging (CT scan or magnetic resonance imaging [MRI ]) to rule out brain metastases
• Signed informed consent that details the investigational nature of the study according to institutional and federal guidelines
• Registered with Clinical Trials Office at Karmanos Cancer Institute/Wayne State University

Exclusion criteria

• Prior chemotherapy, radiation for any malignancy in which they received any thoracic radiotherapy
• Patients with concurrent malignancy; patients with prior or concurrent malignancy will be allowed as long as the treating physician considers it unlikely to impact the clinical outcome of the patient
• Patients with peripheral neuropathy > 2
• Serious medical illness including but not limited to uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction or cerebrovascular event with 6 months of registration, history of chronic active hepatitis or history of human immunodeficiency virus (HIV) or an active bacterial infection will not be eligible
• Inability or unwillingness to take folic acid or vitamin B12 or dexamethasone
• Pregnant or lactating women; all pre-menopausal and peri-menopausal women should have a urine test for pregnancy within a week of starting therapy; all patients of child bearing potential should agree to use an effective contraceptive method
• Patients should not participate in any other therapeutic investigational study while taking part in this study
• Patients on warfarin will not be allowed on the study; patient on low molecular heparin or anti direct factor Xa inhibitor (Xa) drugs will be allowed
• Patients with a soy allergy will be excluded