Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Cisplatin/Gemcitabine in Patients With Metastatic or Locally Advanced Urothelial Cancer Without Prior Systemic Therapy

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed stage IV transitional cell carcinoma of the urothelium (pure
or mixed) including bladder, urethra, ureter, and renal pelvis

- T4b, any N OR any T, N2-3 OR M1

- Ineligible for surgery or radiotherapy with curative intent

- Measurable or evaluable disease

- No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- WHO 0-1

Life expectancy:

- At least 12 weeks

Hematopoietic:

- WBC at least 3,000/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 10 g/dL

Hepatic:

- Bilirubin less than 1.25 times normal

- AST or ALT less than 2.5 times normal

Renal:

- Glomerular filtration rate at least 60 mL/min

- Calcium normal or clinically insignificant

Cardiovascular:

- No clinically significant cardiac arrhythmia

- No congestive heart failure

- No complete bundle branch block

- No New York Heart Association class III or IV heart disease

Other:

- Not pregnant or nursing

- Negative pregnancy test

- 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 compliance

- No grade 3 or 4 infection without neutropenia

- No other serious concurrent systemic disorder that would preclude study therapy

- No mental disorder that would preclude study compliance

- No grade II or greater neuropathy

- No other prior or concurrent malignancy except appropriately treated carcinoma in
situ of the cervix, basal cell carcinoma of the skin, or incidental prostate cancer
(T1, Gleason score no greater than 6, and PSA less than 0.5 ng/mL)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior investigational biologic agents (e.g., antiangiogenic products, signal
transduction pathway inhibitors, immunomodulators, or monoclonal antibody therapy)

- At least 4 weeks since prior immunotherapy

Chemotherapy:

- No prior systemic chemotherapy

- At least 4 weeks since prior local intravesical chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- See Disease Characteristics

- No more than 1 prior course of radiotherapy

- At least 4 weeks since prior radiotherapy and recovered

Surgery:

- See Disease Characteristics

- Prior urological procedures to relieve urinary tract obstruction and improve renal
function allowed (e.g., ureteral stent or percutaneous nephrostomy)