Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer

OBJECTIVES:

- Determine the maximum tolerated dose of radiotherapy in combination with carboplatin
and paclitaxel in patients with unresectable non-small cell lung cancer.

- Determine the 2-year survival of patients treated with this regimen.

- Determine the progression-free local control rate in patients treated this regimen.

- Determine the tolerability of this regimen in these patients.

- Assess the quality of life of patients treated with this regimen.

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

Patients undergo radiotherapy* once daily 5 days a week for 7 weeks and 2 days (a total of
37 fractions). Patients concurrently receive paclitaxel IV over 3 hours and carboplatin IV
over 30 minutes once weekly for 7 weeks. Treatment continues in the absence of disease
progression or unacceptable toxicity.

NOTE: *No prophylactic nodal radiotherapy is administered

Cohorts of 3-6 patients receive escalating doses of radiotherapy until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12
additional patients are treated at that dose level in the phase II portion of the study.

Beginning 3 weeks after completion of radiotherapy, patients receive paclitaxel and
carboplatin as above. Treatment repeats every 21 days for 3 courses in the absence of
disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, once during the last week of radiotherapy, and then
every 3 months for 2 years.

Patients are followed at 3 weeks, every 3 months for 21 months, and then every 6 months for
3 years.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Stage I, II, or III NSCLC that is unresectable due to tumor extent or other
medical reasons

- Measurable disease

- Tumor must not exceed volume that would require radiation volumes greater than those
allowed on this study

- No more than blunting of the costophrenic angle on chest x-ray due to pleural
effusions

- No more than small effusions seen on chest CT scan only

- No supraclavicular adenopathy

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-1

Life expectancy:

- At least 12 weeks

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

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

Hepatic:

- Total bilirubin no greater than 1.5 times upper limit of normal (ULN) OR

- Direct bilirubin no greater than 1.5 times ULN

- AST no greater than 3 times ULN

Renal:

- Creatinine clearance at least 40 mL/min

Cardiovascular:

- No New York Heart Association class III or IV heart disease

Pulmonary:

- FEV_1 at least 1 L or 35% of predicted

Other:

- No grade 2 or greater peripheral neuropathy

- No weight loss of 10% or more within the past 3 months

- No uncontrolled infection

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, adequately treated noninvasive carcinoma (carcinoma in
situ), or localized prostate cancer

- No other severe underlying disease that would preclude study participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic:

- No prior biologic therapy for NSCLC

- No concurrent biologic therapy

- No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy:

- No prior chemotherapy for NSCLC

- No other concurrent chemotherapy

Endocrine therapy:

- No prior endocrine therapy for NSCLC

Radiotherapy:

- No prior radiotherapy for NSCLC

Surgery:

- No prior surgery for NSCLC