A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.

Inclusion criteria

• . Age < or = 18 years, patients aged 75 years or more will benefit from a geriatric assessment.
• . Advanced or metastatic urothelial cancer confirmed histologically or cytologically.
• . Patients liable to receive a first -line chemotherapy for advanced or metastatic urothelial carcinoma.
• . Measurable disease according to RECIST criteria V1.1.
• . Patients who received neoadjuvant or adjuvant chemotherapy based on platinum salt must have completed treatment at least 6 months before entering the study.
• . Performance status < or = 2.
• . Life expectancy > 3 months.
• . Patients with creatinine clearance between 40 and 60 ml / min ( according to Cockcroft and Gault ).
• . Patients having no contra-indication to overhydration.
• . Satisfactory hematological tests: Neutrophils > 1.5 G / l Platelets > 150 G / l , hemoglobin ≥ 10 g / dl.
• . Satisfactory liver function tests: total bilirubin < 1.5 x ULN (upper limit of normal), AST (aspartate aminotransferase) and ALT (alanine aminotransferase)<or = 2.5 x ULN (or 5 x ULN if liver metastases).
• . In case of prior radiotherapy, a minimum of 14 days must relapse between the end of radiotherapy and study entry.
• . For women of childbearing age , use an effective contraceptive method to study entry and for the duration of the study and 6 months after the last dose of study treatment ; For sexually active fertile men having a partner of childbearing age using effective contraception for the duration of the study and 6 months after the last dose of study treatment.
• . Patient affiliated to a social security system in France.
• . Patient signed informed consent before inclusion in the study and before any specific procedure for the study.

Exclusion criteria

• . Any concomitant or previous malignancy within 5 years prior to the study ( with the exception of basal cell or squamous cell carcinoma in situ).
• . Pregnant or lactating women.
• . Patients with brain metastases or meningeal or symptoms suggestive of such secondary locations.
• . Bisphosphonate or Denosumab treatment initiated within 28 days prior to randomization into the study or patient who have started such treatment during the study ( a bisphosphonate or denosumab treatment initiated within a period longer than 28 days before randomization may be continued without change during the study ).
• . Other concomitant cancer (radiation therapy, radiopharmaceutical agent chemotherapy).
• . Patients with uncontrolled infection.
• . Patients with peripheral neuropathy grade> 1, whatever the origin or patients with hearing loss.
• . Patient with unstable disease (eg: unstable diabetes, poorly controlled hypertension , congestive heart failure or myocardial infarction within 3 months prior to study entry).
• . Known hypersensitivity to study drugs.
• . Treatment with any other investigational drug within 30 days before inclusion.
• . Any psychological condition , familial, sociological or geographical not to comply with medical monitoring and / or procedures in the study protocol.
• . Patient protected by law.