OBJECTIVES:

Primary

• Determine the overall survival of patients with chemotherapy-naïve advanced or recurrent non-small cell lung cancer treated with gemcitabine, carboplatin, and bortezomib.

Secondary

• Determine the response rate (confirmed and unconfirmed, complete and partial) and progression-free survival of patients with measurable disease treated with this regimen.
• Determine the quantitative toxic effects of this regimen in these patients.
• Correlate levels of hypoxia-induced secreted proteins and tumor DNA in plasma, levels of apoptosis-associated proteins in tumor tissue, and the change in levels of bortezomib-modulated proteins in peripheral white blood cells with response and survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue to receive bortezomib alone on the above schedule for up to 1 year at the discretion of the treating physician.

Patients are followed every 6 months for up to 3 years after registration.

PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study within 5 months.

DISEASE CHARACTERISTICS:

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

  • One of the following disease stages:

    • Selected stage IIIB (T4 due to malignant pleural effusion, any N, M0)
    • Stage IV (any T, any N, M1 [distant metastases present])
    • Recurrent disease after prior surgery and/or radiotherapy

• Measurable or nonmeasurable disease by CT scan, MRI, or x-ray

  • No pleural effusions, ascites, or laboratory parameters as the only evidence of disease
  • Disease must be outside the prior radiation field or a new lesion formed inside the port
• No known brain metastases
• Must be offered participation in SWOG-S9925

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• SGOT or SGPT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No known hypersensitivity to boron, mannitol, or bortezomib
• No greater than grade 1 peripheral neuropathy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic agents for NSCLC
• No concurrent biologic agents

Chemotherapy

• No prior systemic chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 2 weeks since prior thoracic or other major surgery and recovered

Other

• No other concurrent anticancer agents
• No other concurrent investigational drugs
• No concurrent combination antiretroviral therapy for HIV-positive patients