• Efficacy and tolerability of 2 schedules of docetaxel and bortezomib [ Designated as safety issue: Yes ]
  

• Time to progression [ Designated as safety issue: No ]
  
• 1-year and overall survival [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Pharmacokinetics [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the efficacy and tolerability of sequential vs concurrent docetaxel and bortezomib in patients with previously treated, progressive or recurrent, advanced non-small cell lung cancer (NSCLC).

Secondary

• Compare time to progression in patients with previously treated NSCLC treated with these regimens.
• Compare 1-year and overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Determine the pharmacokinetics of docetaxel in the context of this study.

Tertiary

• Determine levels of expression of molecular markers regulated by docetaxel and bortezomib and correlate with clinical response and overall survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1) and number of prior chemotherapy treatments (1 vs ≥ 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Tumor and blood samples are collected periodically for biomarker analysis and pharmacokinetic assays. Immunohistochemistry is used to assess Bcl-2, Bcl-xL, Bax, and NF-kB. Immunoenzyme techniques are used to examine hypoxia-inducible factor 1 (HIF-1), OPN, vascular endothelial growth factor, and PAI-1.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

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

• Progressive or recurrent NSCLC after treatment with 1 prior platinum-based chemotherapy regimen for metastatic disease

  • Prior neoadjuvant/adjuvant chemotherapy and/or concurrent chemoradiation for early-stage disease allowed

• Measurable disease* with ≥ 1 unidimensionally objectively measurable lesion, including any of the following:

  • Lung mass (measurable on chest x-ray, tomograms, or CT scan)
  • Cutaneous nodule
  • Enlarged lymph nodes
  • Liver metastasis (measurable as a discrete focal lesion on radionuclide or CT scan, or ultrasound)
  • Metastatic abdominal mass (measurable on CT scan with ≥ 1 perpendicular diameter ≥ the distance between cuts)

  • Measurable disease must be outside the previous radiation field or a new lesion must be present

    • Progressive disease within a previously radiated field allowed NOTE: *Measurable disease DOES NOT include bone metastases or non-focal liver metastases

• No symptomatic or untreated brain metastasis requiring steroids

  • Asymptomatic, previously treated (surgical resection or radiotherapy) brain metastasis allowed provided they are neurologically stable and ≥ 4 weeks since prior steroids

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine clearance ≥ 50 mL/min
• Creatinine ≤ 1.6 mg/dL
• Bilirubin normal
• AST ≤ 2 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No peripheral neuropathy ≥ grade 2
• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
• No prior docetaxel or bortezomib
• Prior epidermal growth factor receptor inhibitor therapy allowed
• Prior paclitaxel allowed
• At least 4 weeks since prior radiotherapy and recovered
• At least 4 weeks since prior major surgery and recovered
• At least 2 weeks since prior and no concurrent enzyme-inducing anticonvulsants

• No concurrent hormonal therapy, biologic therapy, or radiotherapy to measurable lesions

  • Concurrent palliative radiotherapy to small-field nonindicator lesions (e.g., painful bony metastases) allowed