OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy.
• Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of bortezomib, etoposide, and carboplatin.

Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients with newly diagnosed, chemotherapy-naive extensive stage small cell lung cancer, and 6 patients with other tumor types, are treated at that dose.

PROJECTED ACCRUAL: A total of 12-27 patients will be accrued for this study within 6-14 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor cancer for which no curative therapy exists

• Clinically stable CNS disease is allowed provided the following criteria are met:

  • No uncontrolled brain metastases or CNS involvement
  • No active seizures
  • On stable dose of antiseizure or steroid medication for at least 7 days before study enrollment

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No other serious concurrent systemic disorders (including other malignancy)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow or peripheral blood stem cell transplantation
• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior carboplatin and/or etoposide allowed
• No more than 2 prior courses of mitomycin

Endocrine therapy:

• See Disease Characteristics
• No concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• Palliative radiotherapy involving less than 35% bone marrow reserve allowed if completed at least 2 weeks before study enrollment
• No prior wide-field radiotherapy to 35% or more of bone marrow
• No prior pelvic radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• At least 28 days since prior investigational agents
• No other concurrent experimental medications