Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed transitional cell carcinoma of the urothelium

- Pure or mixed histology

- Upper or lower urinary tract

- Radiologically evaluable* locally advanced and/or metastatic disease not amenable to
curative treatment with surgery or radiotherapy, meeting any 1 of the following
criteria:

- T4b, any N, any M

- Any T, N2-3, any M

- Any T, any N, M1

- NOTE: *Patients enrolled in the phase II portion of the trial must have
radiologically measurable disease.

- No transitional cell cancer for which subsequent radical treatment is being
considered with a view to possibly cure the disease

- No history of CNS metastases

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and ALP ≤ 2.5 times ULN

- PT or INR ≤ 1.5

- GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Fit to receive cisplatin-containing combination chemotherapy

- No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the
cervix, or incidental localized prostate cancer

- No known HIV positivity or chronic hepatitis B or C infection

- No symptomatic coronary artery disease, myocardial infarction within the past 6
months, congestive cardiac failure (NYHA class III or IV disease), or uncontrolled or
symptomatic cardiac arrhythmia

- No clinically significant bacterial or fungal infection

PRIOR CONCURRENT THERAPY:

- At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of
total bone marrow volume

- At least 1 month since prior investigational drug

- No prior systemic therapy for locally advanced or metastatic disease

- Patients who have received prior neoadjuvant or adjuvant chemotherapy for
urothelial cancer (up to 4 courses), completed at least 6 months prior to first
documented disease progression are eligible

- No concurrent anticoagulant therapy with warfarin or unfractionated heparin

- Patients requiring anticoagulation may be entered on study after successful
conversion to low molecular weight heparin

- No concurrent medications which have known adverse interactions with the treatment
used on this trial (e.g., CYP3A4 inhibitors or inducers in phase I of this trial)

- No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio,
Bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)

- No concurrent grapefruit juice