Gemcitabine Hydrochloride and Cisplatin in Treating Patients with High-Grade Urothelial Cancer

Inclusion Criteria

• Histologically confirmed high-grade upper tract transitional cell carcinoma at Memorial Sloan-Kettering Cancer Center (MSKCC) or a participating site and/or 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 a participating site attending urologic oncologist
• Karnofsky performance status >= 70%
• Age >= 18 years of age
• Absolute neutrophil count >= 1500 cells/mm^3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin >= 9.0 g/dL
• Bilirubin =< 1.2
• Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2.5 x upper limit of normal (ULN) for the institution
• Alkaline phosphatase =< 2.5 x ULN for the institution
• Serum creatinine =< 1.3 mg/dL if male or =< 1.1 mg/dL if female OR calculated creatinine clearance >= 55 ml/min/1.73 m^2
• 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 resectable
• Presence of carcinoma in situ (CIS)
• Prior systemic chemotherapy (prior intravesical therapy is allowed)
• Prior radiation therapy to the bladder
• Evidence of New York Heart Association (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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade >= 2
• 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; supportive care trials or non-treatment trials, e.g. quality of life (QOL), are allowed
• Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin (low dose warfarin up to 2 mg orally [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 MSKCC and participating site principal investigator (PI); male patients must be surgically sterile or agree to use effective contraception