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