A Phase I Dose Intensification Study Using Gated Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Patients With Inoperable, Non-Small Cell Lung Cancer

Inclusion Criteria:

- Patients with histologically-proven, by biopsy or cytology, unresectable lung cancer
of the following histologic types: squamous cell carcinoma, adenocarcinoma, large
cell carcinoma, non-small cell carcinoma, not otherwise specified.

- Patient with AJCC Stage IIIA-IIIB, if all detectable tumor can be encompassed by
radiation therapy fields, including both the primary tumor and the involved regional
lymph nodes.

- 18-fluoro-2-deoxyglucose positron emission tomography required for staging and image
fusion for treatment planning.

- Atelectasis, if present, must be less than one lung.

- Patients must have granulocytes >1500/µl; platelets >100,000/µl; bilirubin < 1.5
mg/dl; AST(SGOT) < 2 ULN; serum creatinine < 2.0 mg/dl.

- Zubrod Score 0-1.

- FEV1 must be >1.0 L.

- Patients must sign a study-specific informed consent form prior to study entry

- Patients must have measurable disease on the planning CT.

- Patient must have a completed the IMRT plan and the attending physician must have
reviewed and approved the dose volume histograms as follows (based on treatment
planning to the Phase 4 dose level): total lung V20 < 30%, mean esophageal dose < 34
Gy, the esophageal V55 < 30%, the heart V40 < 50%.

- No prior or concurrent malignancy except non-melanomatous skin cancer unless
disease-free for one year or more; no prior lung cancer within last two years.

- No prior RT to thorax.

- No previous chemotherapy or previous biologic response modifiers for current lung
cancer or within the past five (5) years.

- No distant metastases or supraclavicular lymph node involvement or significant
atelectasis.

- No clinically significant pleural effusions, pericardial effusions or superior vena
cava syndrome.

Exclusion Criteria:

- Undifferentiated small cell (oat cell or high grade neuroendocrine) carcinoma, any
stage.

- Stage I, II or IV NSCLC.

- Complete tumor resection, recurrent disease, or those patients eligible for
definitive surgery.

- Concurrent malignancy except non-melanomatous skin cancer or prior cancer unless
disease-free for one year or more.

- Prior radiation therapy to the thorax.

- Previous chemotherapy or previous biologic response modifiers for current lung cancer
or within the past five (5) years.

- Distant metastases or supraclavicular lymph node involvement, or atelectasis of an
entire lung.

- Patients who have not had the pre-treatment evaluations in Section 4.0 or evaluations
performed > 8 weeks prior to study entry.

- Patients with clinically significant pleural effusions, pericardial effusions or
superior vena cava syndrome.

- Prior lung cancer within the last two years.

- Patients who have significant atelectasis and in whom the CT definition of the gross
tumor volume(GTV) is difficult to determine.

- Pregnant or lactating females. It is not known what effects this treatment may have
on the developing fetus.