Gemcitabine Hydrochloride and Cisplatin Before Surgery in Treating Patients With Muscle Invasive Bladder Cancer

PRIMARY OBJECTIVES:

I. To assess the rate of complete response (pT0) at cystectomy following preoperative dose
dense gemcitabine and cisplatin (DD GC) in patients with muscle invasive urothelial
carcinoma of the bladder.

SECONDARY OBJECTIVES:

I. To assess the toxicity profile of DD GC when given in the neoadjuvant setting: To define
the number of patients who complete all three cycles of treatment without dose reduction,
and to describe the incidence of toxicity.

II. To assess the 5 year overall and relapse free survival in patients who receive
neoadjuvant DD GC.

TERTIARY OBJECTIVES:

I. To evaluate tissue specimens from patients to assess for molecular markers that correlate
with clinical outcome.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and
cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3
courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks
after chemotherapy, patients undergo radical cystectomy.

After completion of study treatment, patients are followed up for 5 years.

Inclusion Criteria:

- Patients must have histologically confirmed urothelial carcinoma of the bladder or
urethra; patients with urothelial carcinoma of the prostatic urethra only may be
included at primary investigator (PI) discretion; T-stage must be T2 to T4a; patients
with radiographic N0 disease or N1 disease are eligible for the study; patients must
not have radiographic evidence of metastatic disease; mixed histologies which are
predominantly urothelial, such as with squamous or micropapillary differentiation,
are allowed so long as there is no component of small cell histology; histology must
be confirmed by a pathologist at an institution involved in this study

- Patients must be candidates for radical cystectomy with the goal of cure

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT])
=< 2.5 X institutional ULN

- Patients must have adequate renal function defined as creatinine clearance >= 50
mL/min; for eligibility, creatinine clearance may be either calculated using the
Cockcroft-Gault formula or measured with 24 hour urine collection; note that 24 hour
urine collection is required at baseline, but does not have to be used for
eligibility if calculated clearance by Cockcroft-Gault is preferred; nephrostomy or
ureteral stent placement in order to achieve adequate creatinine clearance is allowed

- Women of child-bearing potential (WOCBP) and men with a female partner who is a WOCBP
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) starting prior to beginning treatment and continuing until at
least 3 months after last dose of chemotherapy and surgery; should a woman become
pregnant or suspect she is pregnant while participating in this study or if a female
partner of a man participating in this study becomes pregnant, the treating physician
must be notified immediately; WOCBP must have a negative serum or urine pregnancy
test within 7 days prior to initiating study treatment

- No other active malignancy

- Ability to understand and the willingness to sign written informed consent and Health
Insurance Portability and Accountability Act (HIPAA) documents

Exclusion Criteria:

- Patients who have had intravesicular therapy within 4 weeks of study entry, or those
who have not recovered from adverse effects of such agents administered more than 4
weeks earlier

- Patients may not be receiving any investigational agents within 4 weeks of study
entry

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to gemcitabine or cisplatin or other agents used in the study

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study

- Known human immunodeficiency virus (HIV)-positive patients on combination
antiretroviral therapy are ineligible

- Patients who have undergone prior radiation to greater than or equal to 25% of the
bone marrow within the past year are excluded

- Patients who have received any previous systemic chemotherapy or radiation therapy
for urothelial carcinoma within 1 year of study entry are ineligible