Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. Assess the safety and tolerability of this regimen in these patients. II. Determine the
median time to progression in patients treated with this regimen.

III. Determine the median survival duration in patients treated with this regimen.

IV. Assess the safety and efficacy of pegfilgrastim in these patients.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin hydrochloride intravenous (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.

Inclusion Criteria:

- 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

- Patients must sign an informed consent indicating that they are aware of the
investigational nature of this study, in keeping with the policies of the institution.

- 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)

- 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

- All patients must be evaluated in the Department of Genitourinary Medical Oncology at
M. D. Anderson Cancer Center or participating CCOP center prior to signing informed
consent.

- No prior systemic chemotherapy including, adjuvant or neoadjuvant therapy

- Prior intravesicular chemotherapy allowed

Exclusion Criteria:

- No brain metastases

- Not pregnant or nursing

- 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 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

- No uncontrolled severe hypertension

- Renal insufficiency that requires hemodialysis or renal insufficiency that is
reversible in patients with tumor confined to the primary site (i.e., that is
potentially resectable with neoadjuvant chemotherapy).