• Overall response rate (complete and partial response) at 6 and 12 weeks [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Median time to progression [ Designated as safety issue: No ]
  
• Median survival duration [ Designated as safety issue: No ]
  
• Safety [ Designated as safety issue: Yes ]
  
• Efficacy [ Designated as safety issue: No ]
  
• Frequency of neutropenic fever [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Assess the efficacy of gemcitabine hydrochloride, paclitaxel, doxorubicin hydrochloride, and pegfilgrastim, in terms of response rate, in patients with metastatic or unresectable transitional cell carcinoma of the bladder or urinary tract and renal insufficiency.

Secondary

• Assess the safety and tolerability of this regimen in these patients.
• Determine the median time to progression in patients treated with this regimen.
• Determine the median survival duration in patients treated with this regimen.
• Assess the safety and efficacy of pegfilgrastim in these patients.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin hydrochloride IV over 20 minutes, paclitaxel IV over 60 minutes, gemcitabine hydrochloride IV over 90 minutes, and pegfilgrastim subcutaneously on day 1. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 3 years.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed transitional cell carcinoma (TCC) of the bladder, urethra, or upper urinary tract

  • Mixed TCC and variant histologies (i.e., small cell, squamous cell, adenocarcinoma, or sarcoma) allowed if present in < 50% of the biopsy specimen
• Metastatic or unresectable disease

• Measurable disease

  • Measurable disease may include radiographic detection of metastases in lymph nodes (≥ 1.5 cm) or liver or lung (≥ 1.0 cm) OR pelvic mass palpable on examination under anesthesia

• Creatinine clearance < 60 mL/min

  • No renal insufficiency that requires hemodialysis
  • No renal insufficiency that is reversible in patients with tumor confined to the primary site (i.e., that is potentially resectable with neoadjuvant chemotherapy)
• No brain metastases

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• Zubrod performance status 0-2
• Platelet count > 100,000/mm^3
• Absolute granulocyte count > 1,500/mm^3
• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 2 times upper limit of normal
• LVEF > 40% OR normal EKG and no history of cardiac disease
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No severe or uncontrolled infection
• No New York Heart Association class III-IV congestive heart failure, unstable angina, or history of myocardial infarction within the past 6 months
• No peripheral neuropathy ≥ grade 2
• No uncontrolled severe hypertension
• No persistently uncontrolled diabetes mellitus
• No chronic liver disease
• No HIV positivity
• No other malignancy except nonmelanoma skin cancer unless disease-free for the past 3 years
• No overt psychosis, mental disability, or other condition that would preclude giving informed consent
• No known sickle cell disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy including, adjuvant or neoadjuvant therapy

  • Prior intravesicular chemotherapy allowed