• Efficacy of Leukine & Neupogen to prevent grade 3 & 4 neutropenia in patients receiving cisplatin & gemcitabine: assessed before cycles 3 & 5, then at end of treatment.
  
• Safety of Leukine & Neupogen: evaluated before each cycle & blood work is evaluated weekly throughout the study.
  

• Reduction of grade 3 & 4 hematologic toxicities: evaluated weekly throughout the study.
  
• Reduction of clinical hematologic toxicity including the # of: hospital days required for febrile neutropenia, transfusions & bleeding events, & days of outpatient antibiotics: evaluated throughout the study treatment and until resolved.
  
• Reduction of non-hematologic toxicities: evaluated prior to each cycle.
  
• Enhancement of anti-tumor effects (CR & PR, time to progression, OS & DFS): assessed before cycles 3 & 5, then on day 22 of cycle 6.
  
• Dose intensity as planned vs administered: assessed during each treatment.
  
• Quality of life: evaluated at baseline, pre-cylces 3 & 5, & end of treatment.
  

Objectives: To compare the efficacy of Leukine and Neupogen in the treatment of patients receiving cisplatin and gemcitabine for regionally advanced or metastatic urothelial cancer in regard to reduction of grade 3 and 4 neutropenia. Secondary objectives include a comparison of: hematologic and non-hematologic toxicities, anti-tumor effects, dose intensity, and quality of life in each treatment arm.

Methodology: The study will be a multi-institutional, randomized, phase III study in patients with regionally advanced or metastatic urothelial cancer. All patients will receive chemotherapy with cisplatin plus gemcitabine for six 21-day cycles. Patients will receive hematopoietic growth factor support with either Leukine (Arm A), or Neupogen (Arm B). Rates of anti-tumor responses and the incidence of toxicities in each treatment arm will provide a comparison of efficacy and safety for the hematopoietic support regimens.

Patient Population: Patients to be enrolled (n=100) in this study will have received a diagnosis of regionally advanced or metastatic urothelial cancer of the bladder, ureter, or renal pelvis and will have not undergone previous systemic chemotherapy. Approximately 50 patients will be enrolled into each treatment arm.

Main Criteria for Inclusion: Inclusion criteria for this study specify that patients have evaluable, biopsy-proven, surgically unresectable, regionally advanced, or metastatic urothelial cancer of the bladder, ureter, or renal pelvis. Additionally, patients must have an Eastern Cooperative Oncology Group performance status of 0-2 and adequate bone marrow, renal, and hepatic function. Patients who have undergone previous systemic chemotherapy will be excluded from this study.

Test Product, Dose, Mode of Administration: All patients will receive chemotherapeutic treatment with cisplatin (70 mg/kg) intravenously on Day 1 and gemcitabine (1000 mg/m2) intravenously on Days 1, 8, and 15 of each 21-day cycle. Patients will be randomized to receive either Leukine (250 µg/m2) or Neupogen (5 µg/kg) subcutaneously on Days 2-6, 9-13, and 16-20 of each cycle.

Duration of Treatment: Patients will receive a maximum of six 21-day cycles of treatment. The overall trial, including follow-up, is expected to be 3 years in duration.

Criteria for Evaluation: Efficacy will be assessed by, incidence of grade 3 and 4 toxicities, evaluation of complete and partial response, time to progression, overall and disease specific survival, planned vs administered doses, and quality of life. Safety will be assessed by, vital signs, physical examinations, clinical laboratory evaluations, and the reporting of adverse events.