Gefitinib, Docetaxel, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer

OBJECTIVES:

- Determine the maximum tolerated dose of docetaxel that can be safely delivered in
combination with gefitinib and a definitive course of 3-D planned thoracic radiotherapy
in patients with stage III non-small cell lung cancer.

OUTLINE: This is a dose-escalation study of docetaxel.

- Chemoradiotherapy: Patients receive concurrent chemoradiotherapy comprising docetaxel
IV over 30 minutes on day 1 and thoracic radiotherapy once daily on days 1-5 in weeks
1-7 in the absence of disease progression or unacceptable toxicity.

- Consolidation chemotherapy: Beginning 2 weeks after the completion of
chemoradiotherapy, patients receive consolidation chemotherapy comprising docetaxel IV
over 60 minutes on days 1 and 22.

- Gefitinib therapy: Patients also receive oral gefitinib once daily beginning at the
start of chemoradiotherapy and continuing for up to 1 year* in the absence of disease
progression.

NOTE: *Patients continue to receive gefitinib during the 2-week rest period between
chemoradiotherapy and consolidation chemotherapy.

Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.

Tumor tissue is tested to determine correlation between epidermal growth factor receptor
presence and response to treatment.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 45 patients will be accrued in this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC),
including any of the following:

- Squamous cell carcinoma

- Adenocarcinoma (including bronchoalveolar cell)

- Large cell anaplastic carcinoma (including giant and clear cell carcinomas)

- Stage IIIA/B disease

- Unresectable disease

- Tumors adjacent to a vertebral body allowed

- No demonstrable bone invasion

- All gross disease must be able to be encompassed in the radiation boost
field in accordance with the homogeneity criteria

- Contralateral mediastinal disease (N3) allowed if all gross disease can be
encompassed in the radiation boost field in accordance with the homogeneity
criteria

- No scalene, supraclavicular, or contralateral hilar node involvement

- Pleural effusion allowed if it is transudate, cytologically negative, and
non-bloody AND tumor can be encompassed within a reasonable field of
radiotherapy

- No exudative, bloody, or cytologically malignant effusions

- Pleural effusion seen on chest CT scan but not on chest x-ray and too small
to tap allowed

- Measurable disease, defined as lesions that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques
or as ≥ 10 mm with spiral CT scan

- No nonmeasurable disease, including any of the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Tumor lesions situated in a previously irradiated area

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Granulocyte count ≥ 1,500/mm^3

- Hemoglobin > 8.0 g/dL

- Platelet count ≥ 100,000/mm^3

- Bilirubin < 1.5 mg/dL

- Creatinine < 1.5 times upper limit of normal (ULN)

- Meets 1 of the following criteria:

- AST and ALT < 2 times ULN

- AST and ALT ≤ 2.5 times ULN AND alkaline phosphatase (AP) normal

- AST and ALT normal AND AP ≤ 4 times ULN

- FEV_1 ≥ 1.2 L

- No other currently active malignancy except nonmelanoma skin cancers

- Patients are not considered to have another currently active malignancy if they
have completed therapy for the other malignancy and are considered by their
physician to be at < 30% risk of relapse (i.e., after treatment for early-stage
prostate cancer)

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 3 months after
completing treatment

- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80

- No known severe hypersensitivity to gefitinib or any of the excipients of this
product

- No evidence of severe or uncontrolled systemic disease (e.g., unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease)

- No evidence of any other significant clinical disorder or laboratory finding that
would limit compliance with study requirements

- No evidence of clinically active interstitial lung disease (asymptomatic, chronic
stable radiographic changes allowed)

- No peripheral neuropathy ≥ grade 1

PRIOR CONCURRENT THERAPY:

- At least 2 weeks since prior formal exploratory thoracotomy

- No prior chemotherapy or radiotherapy for NSCLC

- No prior epidermal growth factor-targeting drugs (i.e., gefitinib, erlotinib, or
cetuximab)

- No other investigational agent within 30 days of study entry

- No concurrent phenytoin, carbamazepine, rifampicin, barbiturates, or Hypericum
perforatum (St John's wort)

- No other concurrent hormonal therapy or chemotherapy except for the following:

- Steroids for adrenal failure, allergic reactions, or septic shock

- Hormones for nondisease-related conditions (e.g., insulin for diabetes)

- Glucocorticosteroids as anti-emetics