Inclusion Criteria:

- Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC
or Penn State Hershey Medical Center radiographically visible tumor stage T2-T4a N0/X
M0 disease with positive selective urinary cytology. Hydronephrosis associated with
tumor on imaging or biopsy will be considered invasive by definition.

- Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per
MSKCC or Penn State Hershey Medical Center attending urologic oncologist

- Karnofsky Performance Status ≥ 70%

- Age ≥ 18 years of age

- Required Initial Laboratory Values:

- Absolute neutrophil count ≥ 1500 cells/mm3

- Platelets ≥ 100,000 cells/mm3

- Hemoglobin ≥ 9.0g/dL

- Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution

- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the
institution

- Alkaline phosphatase ≤ 2.5 x ULN for the institution

- Serum creatinine ≤ 1.5 mg/dL and calculated creatinine clearance ≥ 55 If female
of childbearing potential, serum pregnancy test is negative.

- Patients with reproductive potential must use an effective method to avoid pregnancy
for the duration of the trial.

ml/min/1.73m2 using the formula: CKD epi : GFR = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209
X 0.993Age X 1.018 [if female] X 1.159 [if black]

- Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for
females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max
indicates the maximum of Scr/k or 1.

- If female of childbearing potential, serum pregnancy test is negative.

- Patients with reproductive potential must use an effective method to avoid pregnancy
for the duration of the trial

Exclusion Criteria:

- Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and
surgically unresectable.

- Presence or history of carcinoma in situ (CIS)

- Prior systemic chemotherapy (prior intravesical therapy is allowed)

- Prior radiation therapy to the bladder

- Evidence of NYHA functional class III or IV heart disease.

- Serious intercurrent medical or psychiatric illness, including serious active
infection.

- Preexisting sensory grade 3 neuropathy

- Major surgery or radiation therapy < 4 weeks of starting study treatment.

- Concomitant use of any other investigational drugs

- Any of the following within the 6 months prior to study drug administration:

myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
attack, or pulmonary embolism.

- Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2.

- Prolonged QTc interval on baseline EKG (>450 msec for males and >470 msec for
females).

- Uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy).

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection. Patients with HIV but no evidence
of AIDS will be considered candidates.

- Concurrent treatment on another clinical trial involving an intervention which may
affect the primary endpoint. Supportive care trials or non-treatment trials, e.g.
QOL, are allowed.

- Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin
(low dose warfarin up to 2 mg po daily or use of subcutaneous low molecular weight
heparin for thromboembolic prophylaxis is allowed).

- Pregnancy or breast-feeding. Patients must be surgically sterile or be
postmenopausal, or must agree to use effective contraception during the period of
therapy. The definition of effective contraception will be based on the judgment of
the principal investigator or a designated associate. Male patients must be
surgically sterile or agree to use effective contraception