Phase II Trial of Neoadjuvant Dose Dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer

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 PI discretion. T-stage must be T2 to T4a. Patients with clinical N0 disease or cN1 disease are eligible for the study. Patients should have no 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.
• Age >18 years.
• ECOG performance status of 0 or 1
• Patients must have normal hepatic and marrow function as defined below:

leukocytes ≥ 3,000/mcL absolute neutrophil count ≥ 1,500/mcL platelets ≥ 100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(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 Cockroft-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 Cockroft-Gault is preferred. Neprostomy or ureteral stent placement in order to achieve adequate creatinine clearance is allowed.
• The effects of DD-GC on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because the chemotherapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men with female partner who are WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting at or before the pre-study pregnancy test and continuing until at least 3 months after last study both chemotherapy and surgery. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. WOCBP must have a negative serum or urine pregnancy test within 7 days prior to study entry.
• No other active malignancy.
• Ability to understand and the willingness to sign written informed consent and 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 due to the potential for teratogenic or abortifacient effects of cytotoxic chemotherapy.
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Patients who have undergone prior radiation to greater than or equal to 25% of the bone marrow within the past year are excluded due to risk of life threatening myelosuppression.
• Patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma within 1 year of study entry are ineligible.