Neoadjuvant Gemcitabine and Fractionated, Weekly Cisplatin For Muscle Invasive Bladder Cancer and Patients Not Candidates For High Dose Cisplatin

Inclusion Criteria:

1. Pathologically confirmed muscle-invasive urothelial (transitional cell) carcinoma of
the bladder or upper genitourinary tract.

2. Stage T2-T4a. Patients may have nodal disease but there must be no evidence of
distant metastases and patients must be candidates for radical cystectomy as
determined by urologic surgeon (note from/confirmation by surgeon required).

3. No prior systemic therapy for urothelial carcinoma. Prior intravesical therapy is
allowed.

4. Patients are determined by their treating oncologist to not be a candidate high dose
cisplatin (> 70mg/m2) due to medical comorbidities.

5. Creatinine Clearance (CrCL or eCCr)) > 25 mL/min calculated using the Cockcroft-Gault
formula

6. Patients without serious medical risk factors involving any of the major organ
systems such that the investigator considers it unsafe for the patient to receive the
protocol treatment of this study with gemcitabine and weekly fractionated cisplatin.

7. Preexisting neuropathy < grade 2.

8. No prior invasive malignancy within the prior two years. However, prior history of
non-muscle invasive bladder cancer and patients with an early stage malignancy that
is not expected to require treatment in the next 2 years (such as early stage,
resected breast cancer, or asymptomatic prostate cancer) are eligible.

9. ECOG performance status 0 or 1.

10. Age ≥ 18 years of age.

11. Not pregnant and not nursing. Women of child bearing potential must have a negative
serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of
HCG) within 7 days prior to beginning of treatment. Post-menopausal women (surgical
menopause or lack of menses >12 months) do not need to have a pregnancy test, please
document status.

12. Required Initial Laboratory Values:

- Neutrophils ≥ 1,000/μl

- Platelet count ≥ 100,000/μl

- Total bilirubin ≤ 1.5 x ULN.

- AST (SGOT) & ALT (SGPT) ≤ 3.0 x ULN

Exclusion Criteria:

1. Metastatic disease.

2. Prior hypersensitivity to platinums that in the investigators opinion would put the
patient at risk if re-exposed

3. Small cell cancer of the bladder or pure adenocarcinoma. Patients with mixed
histologies such as urothelial carcinoma with sarcomatoid features, squamous
differentiation or adenocarcinoma are allowed as long as transitional cell cancer is
the predominant pathologic subtype.