OBJECTIVES:

Primary

• Determine the efficacy of bortezomib, in terms of the response rate, in patients with previously treated advanced transitional cell carcinoma of the urothelium.

Secondary

• Determine the duration of objective response in patients treated with this drug.
• Determine the progression-free and overall survival of patients treated with this drug.
• Determine the safety and toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with a solitary site of disease (i.e., lung or nodal metastases) and who have a partial response (PR) may be considered for surgical resection. Patients with a PR with residual disease after salvage surgery are eligible to continue study therapy. Patients who achieve a complete response, either through resection or bortezomib therapy, receive 2 additional courses of study therapy.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 15-40 patients will be accrued for this study within 13-17 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis

• Previously treated with 1 prior systemic chemotherapy* for advanced or metastatic disease

  • Progressive disease during or after chemotherapy regimen

  • Must have included at least 1 of the following agents:

    • Cisplatin
    • Carboplatin
    • Paclitaxel
    • Gemcitabine
    • Docetaxel NOTE: *Neoadjuvant and adjuvant combination chemotherapy is considered a systemic chemotherapy, while radiosensitizing single-agent chemotherapy is not

• Unidimensionally measurable disease

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  • Nonmeasurable disease includes the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Primary bladder masses
• No known active brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 8 g/dL

Hepatic

• Bilirubin less than 1.8 g/dL
• AST and ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 2.5 mg/dL OR
• Creatinine clearance greater than 30 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study treatment
• Standard chemistry panel normal
• No peripheral neuropathy greater than grade 1

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy

• No concurrent hormonal therapy except for the following:

  • Steroids for adrenal failure
  • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
  • Intermittent dexamethasone as an antiemetic

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent palliative radiotherapy

Surgery

• Not specified

Other

• No prior bortezomib or other proteasome inhibitors

• No prior investigational agents as a single-agent therapy

  • Prior investigational agents incorporated into prior systemic chemotherapy allowed