Neoadjuvant Dose Dense MVAC in MIBC and Locally Advanced Urothelial Carcinoma

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed urothelial cancer of bladder.
2. Locally advanced status for planning surgical treatment (Bladder, confirm muscle invasiveness using TURBT, or cT3-4a and N1-3 using imaging studies)
3. Age 18 years or older
4. Eastern Cooperative Oncology Group performance status 0-1
5. Adequate organ and bone marrow function for cisplatin based chemotherapy

   A. Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9 g/dL)

   B. Adequate renal function: creatinine \< 1.5 x upper normal limit (UNL) or creatinine clearance(Ccr) using Cockroft and Gault formula ≥ 50 ml/min

   C. Adequate hepatic function: bilirubin \< 1.5 x UNL, AST/ALT levels \<5.0 x UNL, alkaline phosphatase \< 5 x UNL (except in case of bone metastasis without any liver disease)
6. Women should use contraceptive medication for 6 months after the end of the study or she would be post-menopause status. Men should consent with the contraception for 6 months after the end of the study or he would be infertile.
7. Patients should sign a written informed consent before study entry.

Exclusion Criteria:

1. Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
2. Excess of 4 weeks after initial imaging studies. But, allow the patients to enrollment of study if they is reassessed and reconfirm the localized status using subsequent imaging studies. In this case, clinical stage is decided as following imaging studies.
3. Prior systemic chemotherapy (But prior intravesical chemotherapy was allowed)
4. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
5. History of treatment with drugs of another clinical trial within 30 days before enrollment.
6. Concomitant severe medical, surgical, or psychiatric disease or problems which can affect the results of the clinical trial or have possibilities of unexpected medical problems caused be the drug of clinical trial

   A. Unstable angina, myocardial infarction, uncontrolled arrhythmias, symptomatic angina pectoris, cardiac failure within the previous 6 months

   B. Active infection which would compromise the patients

   C. Liver cirrohosis or chronic active hepatitis

   D. Poor pulmonary function (DLCO ≤ 50% of normal or resting O2 saturation ≤ 90%)

   E. Clinically significant hemoptysis or gastrointestinal bleeding within previous 6 months

   F. Major psychiatric disorders or other inadequate psychiatric problems according to the physicians decision
7. History of another malignancy (but treated malignancy at least two years before enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid carcinoma are allowed even diagnosed less than 2 years before enrollment).
8. Pregnant or lactating women, women of childbearing potential not employing adequate contraception