Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed transitional cell carcinoma of the urothelium
• •* Pure or mixed histology
• •* Upper or lower urinary tract
• •Radiologically evaluable\* locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy, meeting any 1 of the following criteria:
• •* T4b, any N, any M
• •* Any T, N2-3, any M
• •* Any T, any N, M1
• •NOTE: \*Patients enrolled in the phase II portion of the trial must have radiologically measurable disease.
• •No transitional cell cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease
• •No history of CNS metastases
• •PATIENT CHARACTERISTICS:
• •WHO performance status 0-2
• •Life expectancy ≥ 3 months
• •Absolute neutrophil count ≥ 1.5 x 10\^9/L
• •Platelet count ≥ 100 x 10\^9/L
• •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• •ALT and ALP ≤ 2.5 times ULN
• •PT or INR ≤ 1.5
• •GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •Fit to receive cisplatin-containing combination chemotherapy
• •No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer
• •No known HIV positivity or chronic hepatitis B or C infection
• •No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III or IV disease), or uncontrolled or symptomatic cardiac arrhythmia
• •No clinically significant bacterial or fungal infection
• •PRIOR CONCURRENT THERAPY:
• •At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume
• •At least 1 month since prior investigational drug
• •No prior systemic therapy for locally advanced or metastatic disease
• •* Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression are eligible
• •No concurrent anticoagulant therapy with warfarin or unfractionated heparin
• •* Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin
• •No concurrent medications which have known adverse interactions with the treatment used on this trial (e.g., CYP3A4 inhibitors or inducers in phase I of this trial)
• •No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, Bacille Calmette-Guérin \[BCG\], yellow fever, varicella, and TY21a typhoid vaccines)
• •No concurrent grapefruit juice