Pemetrexed or Erlotinib as Second-Line Therapy in Treating Patients With Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

• Histologically confirmed non-small cell lung cancer (NSCLC), either oninitial diagnosis or at the time of disease recurrence/progression

  • Mixed histology allowed if all components are consistent with NSCLC
• Recurrent or progressive disease

• Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques or as ≥ 1.0 cm by spiral CT scan

  • Measurable disease must be outside of any previously irradiated treatment field(s) unless there is disease progression or recurrence within the irradiated field(s)

  • No nonmeasurable disease only, defined as any of the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
    • Single disease site in prior radiotherapy field
• Tumor tissue samples must be available and adequate for epidermal growth factor receptor (EGFR) evaluation by FISH

• Previously treated with only one cytotoxic chemotherapy regimen for advanced disease

  • Neoadjuvant/adjuvant cytotoxic chemotherapy administered< 12 months (from date chemotherapy was started) prior to study entry will be counted as one prior treatment
  • Neoadjuvant/adjuvant chemotherapy administered ≥ 12 months prior to study entry and use of targeted agents (e.g., monoclonal antibodies) will not be counted as one prior treatment
• No symptomatic serosal effusion (≥ grade 2 dyspnea as measured by CTCAE v3.0) that is not amenable to drainage

• No brain metastasis, unless the following criteria are met:

  • Brain metastasis is stable and has been previously treated with either whole-brain radiotherapy or gamma-knife surgery
  • More than 14 days since prior steroid treatment
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Total bilirubin normal (ULN) OR direct bilirubinnormal
• AST and ALT ≤ 2.5 times ULN
• INR ≤ 1.5
• Creatinine clearance ≥ 45 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take folic acid, vitamin B_12 supplementation, and dexamethasone
• No known HIV positivity
• No clinically significant infection
• No impaired gastrointestinal (GI) function, inability to swallow pills in the absence of a feeding tube, or GI disease that may significantly alter absorption of oral medications (e.g., ulcerative disease, uncontrolled nausea and vomiting, malabsorption syndromes, or bowel obstruction)
• No serious condition that, in the opinion of the investigator, would preclude the patient's ability to complete the study therapy or increase the risk for serious adverse events

• No other invasive malignant solid tumor or hematologic malignancy, except for any of the following:

  • Prior carcinoma in situ, regardless of organ involvement, or nonmelanoma cutaneous carcinoma that was definitively treated ≥ 3 years ago with no subsequent evidence of recurrence

  • Other prior malignancy diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence

    • Prior breast cancer that was definitively treated > 5 years ago allowed provided patient is not receiving aromatase inhibitors

    • Prio rlow-grade (Gleason score ≤ 6) localized prostate cancer that was diagnosed < 3 years ago allowed

      • Concurrent medications to maintain disease remission allowed

• No concurrent severe and/or uncontrolled medical condition, including any of the following:

  • Angina pectoris
  • Congestive heart failure within the past 3 months, unless ejection fraction > 40%
  • Myocardial infarction within the past 6 months
  • Cardiac arrhythmia
  • Diabetes mellitus
  • Hypertension
  • Any other severe underlying disease that, in the judgment of the investigator, would preclude study entry
• No respiratory symptoms > CTCAE grade 1
• No significant traumatic injury within the past 4 weeks
• No concurrent prophylactic colony-stimulating factors
• Recovered from prior radiotherapy, except for alopecia
• No prior radiotherapy to > 25% of bone marrow
• No prior EGFR tyrosine kinase inhibitors or pemetrexed disodium
• More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
• More than 2 weeks since prior immunotherapy, gene therapy, or other biologic therapy
• More than 2 weeks since prior limited-field radiotherapy (4 weeks for full-field radiotherapy)
• More than 2 weeks since prior minor surgery*
• More than 4 weeks since prior major surgery (i.e., laparotomy)* or open biopsy
• More than 4 weeks since prior hormonal therapy
• More than 4 weeks since prior and no other concurrent ancillary therapy considered investigational (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation)
• No aspirin dose ≥ 1.3 g/day for ≥ 10days before, during, and for ≥ 10 days after treatment with pemetrexed disodium

• No other concurrent chemotherapy, immunotherapy, hormonal therapy, or radiotherapy

  • Radiotherapy for symptom palliation (e.g., painful pre-existing bony metastasis) allowed
• No other concurrent anticancer therapy
• No concurrent major surgery
• No concurrent antiretroviral therapy