Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer

OBJECTIVES:

- Determine the maximum tolerated dose of 3-dimensional conformal radiotherapy when
administered concurrently with paclitaxel and carboplatin in patients with inoperable
stage IIIA or IIIB non-small cell lung cancer. (Phase I) (Closed to accrual as of
01/13/04.)

- Determine the 12-month survival rate in patients treated with this regimen. (Phase II)
(Closed to accrual as of 11/27/07.)

- Determine the toxicity of this regimen in these patients.

- Determine the partial organ tolerance doses for the lung and esophagus in patients
treated with this regimen.

- Determine the complete response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of 3-dimensional conformal
radiotherapy.

- Phase I (closed to accrual as of 01/13/04): Patients undergo 3-dimensional conformal
radiotherapy once daily five days a week for 7-8 weeks. Patients also receive concurrent
chemotherapy comprising paclitaxel IV over 1 hour followed by carboplatin IV over 30
minutes on days 1, 8, 15, 22, 29, 36, and 43.

Cohorts of 7-9 patients receive de-escalating doses of 3-dimensional conformal radiotherapy
until the maximum tolerated dose (MTD) is determined when given in combination with
chemotherapy. The MTD is defined as the highest dose at which no more than 1 patient
experiences dose-limiting toxicity.

- Phase II: Additional patients are accrued and treated as above at the MTD. At least 3
weeks after completing radiotherapy, patients may receive additional chemotherapy
comprising paclitaxel IV over 3 hours once and carboplatin IV over 30 minutes once.
Treatment with paclitaxel and carboplatin may repeat every 3 weeks for up to 2 courses.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months
for 3-5 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 73 patients (up to 27 for phase I [closed to accrual as of
10/28/04] and 46 for phase II) will be accrued for this study within 1-1.5 years.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed unresectable stage IIIB non-small cell lung
cancer

- Squamous cell carcinoma

- Adenocarcinoma

- Large cell carcinoma

- Non-small cell carcinoma not otherwise specified

- All detectable primary tumor and involved regional lymph nodes must be encompassed by
radiotherapy fields

- Measurable disease on 3-dimensional planning CT scan

- No undifferentiated small cell (oat cell or high-grade neuroendocrine) carcinoma

- No stage IV or recurrent disease

- No distant metastases or supraclavicular lymph node involvement

- No significant atelectasis (i.e., atelectasis of an entire lung)

- No pleural effusions, pericardial effusions, or superior vena cava syndrome

- No lung cancer within the past 2 years

- Ineligible for currently open Radiation Therapy Oncology Group (RTOG) phase III lung
protocols

PATIENT CHARACTERISTICS:

Age:

- Not specified

Performance status:

- Zubrod 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin less than 1.5 mg/dL

- Aspartate aminotransferase (AST) less than 2 times upper limit of normal

Renal:

- Creatinine no greater than 2.0 mg/dL

Pulmonary:

- Forced expiratory volume (FEV)_1 at least 1.0 L

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No weight loss greater than 5% in the past 6 months

- No other malignancy within the past year except nonmelanoma skin cancer

- Completed 3D plan with total lung V20 esophageal V55
PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior biologic response modifiers for current lung cancer

- At least 5 years since prior biologic response modifiers

Chemotherapy:

- No prior chemotherapy for current lung cancer

- At least 5 years since prior chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- See Disease Characteristics

- No prior radiotherapy to the thorax

Surgery:

- No prior complete tumor resection