This clinical trial is studying how well erlotinib works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PRIMARY OBJECTIVES:

I. Prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response to OSI-774 (Erlotinib) in this population.

SECONDARY OBJECTIVES:

I. Estimate antitumor objective response rate per RECIST. II. Estimate disease control rate (CR+PR+SD). III. Estimate time to progression and overall survival. IV. Estimate if a grade 2 rash is a predictor of response to OSI-774 (Erlotinib) and of patient survival.

V. Assess safety profile of OSI-774 (Erlotinib) in this population. VI. To determine whether smoking status is linked to outcome for advanced NSCLC patients treated with OSI-774 (Erlotinib).

OUTLINE: This is a pilot, multicenter study.

Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients complete the Smoking Status Survey, a questionnaire regarding smoking habits, at baseline, and then every 3 months during study 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 129 patients will be accrued for this study within 6 months.

Inclusion Criteria:

• Patients must have pathologically confirmed NSCLC

• Patients must have diagnostic specimen available on paraffin-embedded block

• Patients must have advanced NSCLC (stage IIIB with a malignant pleural effusion or IV disease, or recurrent disease)

• Patients must not have received prior chemotherapy or targeted therapy for metastatic disease, including no prior EGFR inhibitor; patient may have received adjuvant chemotherapy for early stage disease (IB-IIIA), or chemo/XRT for stage IIIA or IIIB disease, provided s/he meets all of the following:

  • It has been at least 6 months since completion of patient's adjuvant chemotherapy for early stage disease (IB-IIIA) or chemo/XRT for stage IIIA or IIIB disease
  • Patient now has advanced disease

• Patients must have measurable disease per RECIST criteria; all sites of disease must be assessed within 4 weeks prior to registration

• Creatinine < 1.5 mg/dL or a creatinine clearance of > 50 mL/min

• SGOT(AST) and SGPT(ALT) < 2 x the institution's upper limit of normal

• Bilirubin < 1.5 mg/dL

• ANC > 1500/mm^3

• PLT > 100,000/mm^3

• Patients must have ECOG performance status 0, 1, or 2

• Patients with stable, treated brain metastases are eligible (defined as: patients with brain metastases must have been treated and are asymptomatic and are no longer taking corticosteroids)

• Patients with gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease, are ineligible

• Pregnant and breast feeding women are excluded from the study because the agent used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk

• Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) for the duration of the study

• HIV positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 (Erlotinib)

• Patients must not have had immuno, hormonal or radiation therapy within 2 weeks prior to entering the study; those who have not recovered from adverse events due to agents administered more than 2 weeks earlier are ineligible; previously irradiated areas can be considered "measurable disease" if there has been documented progression

• Patients must not have ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements

• Patients must not have serious non-healing wound, or bone fracture, or major surgical procedure within 21 days prior to study entry

• Patients taking Warfarin are eligible

• If the patient is taking Cyp3A4 inducers or inhibitors, they must be discontinued one week prior to starting OSI-774 (Erlotinib)

• Patients must not be enrolled in any other concurrent clinical trials