Dose Dense MVAC for Muscle Invasive Bladder Cancer

Primary Objective To assess the rate of complete response (pT0) at cystectomy or ureterectomy following preoperative dose dense MVAC (DD-MVAC) in patients with muscle invasive urothelial carcinoma of the bladder or high grade upper tract urothelial carcinoma. Secondary Objectives To assess the toxicity profile of DD-MVAC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to compare incidence of toxicity to the historical standard described by Grossman et al. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD-MVAC. To compare complete response rates between the following subgroups of study patients: Among bladder patients: Clinical N0 versus N1 (Appendix B) Among bladder patients: T2 stage without high risk features versus T2 with high risk features plus those with \> T2 stage. Three 14 day cycles of: Methotrexate 30 mg/m2 IV push or infusion over 2-3 minutes. Day 1 Vinblastine 3 mg/m2 Slow IV push or infusion over Day 1 Doxorubicin 30 mg/m2 Slow IV push or infusion over 15 minutes Day 1 Cisplatin 70 mg/m2 IV infusion over 4 hours Note: May divide dose over two sequential days (35 mg/m2/d x 2 days) if creatinine clearance 50-59 mL/min Day 1\* (or divided over Day 1 and Day 2) Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy. Followed in 4-8 weeks by radical cystectomy/ureterectomy.