• Duration of survival [ Designated as safety issue: No ]
  

• Response as assessed by RECIST criteria [ Designated as safety issue: No ]
  
• Toxicity as assessed by CTC v2 [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Compare the antitumor activity of gemcitabine and carboplatin vs methotrexate, carboplatin, and vinblastine in patients with transitional cell cancer of the urothelium who are ineligible for cisplatin-based chemotherapy.
• Compare the toxicity and acute and intermediate (1-2 years) side effects of these regimens in these patients.
• Compare the complete response rates, progression-free survival, and overall survival of patients treated with these regimens.
• Compare the symptoms and quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive methotrexate* IV and vinblastine IV on days 1, 15, and 22 and carboplatin IV over 1 hour on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: * Methotrexate is omitted for patients with pleural effusion or ascites until complete resolution and for patients with a glomerular filtration rate less than 30 mL/min or creatinine greater than 2 mg/dL

Patients in either arm who achieve a complete response (CR) receive 2 additional courses of chemotherapy beyond CR.

Quality of life is assessed at baseline, after every 2 courses of chemotherapy, and within 6 weeks of completion of therapy.

Patients are followed within 6 weeks, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 156 patients (78 per treatment arm) will be accrued for the phase II portion of this study. A total of 225 patients will be accrued for the phase II + III portions of this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell cancer of the urothelium, including the renal pelvis, ureters, urinary bladder, and urethra, meeting 1 of the following criteria:

  • Unresected positive lymph node
  • Distant metastases (M1, stage IV)
  • Unresectable primary bladder cancer (T3-4)
• Measurable disease

• Ineligible for cisplatin-based chemotherapy and presenting with the following:

  • WHO performance status 2 AND/OR
  • Glomerular filtration rate greater than 30 mL/min but less than 60 mL/min
• No brain metastases or other CNS lesions

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• See Disease Characteristics

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 125,000/mm^3

Hepatic:

• Bilirubin no greater than 1.25 times normal
• AST/ALT no greater than 3 times normal (5 times normal if liver metastases are present)

Renal:

• See Disease Characteristics
• Calcium normal

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after study participation
• No psychological, familial, sociological, or geographical condition that would preclude study participation
• No other prior or concurrent malignancy except cured basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior systemic biologic therapy

Chemotherapy:

• See Disease Characteristics
• No prior systemic cytotoxic therapy (including adjuvant and neoadjuvant chemotherapy)

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 months since prior radiotherapy
• Prior radiotherapy to study lesions allowed if there is evidence of disease progression

Surgery:

• Not specified