Lapatinib, Cisplatin, Gemcitabine as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urothelial Cancer

DISEASE CHARACTERISTICS:

• Histologically proven transitional cell carcinoma of the urothelial tract
• Metastatic or locally advanced disease
• Measurable disease according to RECIST
• Involvement of at least one target not in previously irradiated fields
• Overexpressing HER1 and/or HER2 receptors (HER2 3+ by IHC OR HER2 FISH or CISH positive)
• No clinical signs of CNS involvement

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• ANC ≥ 1,500/mm³
• Thrombocytes > 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST/ALT ≤ 3 times ULN
• Creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 3 months after completion of study treatment
• Cardiac ejection fraction normal
• Normal 12 lead ECG
• No serious cardiac illness or medical condition within the past 6 months including, but not limited to, any of the following:
• Documented congestive heart failure
• High-risk uncontrolled arrhythmias
• Angina pectoris requiring antianginal medication
• Clinically significant valvular heart disease
• Evidence of transmural infarction on ECG
• Poorly controlled hypertension (e.g., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
• No peripheral neuropathy > grade 1
• Able to swallow and retain oral medication
• No other malignancy within the past 3 years except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• No active or uncontrolled infections, serious illnesses, malabsorption syndrome or medical conditions, hepatitis, HIV, and/or cirrhosis
• No psychological, familial, sociological, or geographical condition potentially hampering study protocol compliance or follow-up schedule
• No current active hepatic or biliary disease (with the exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver metastases or stable chronic liver disease)

PRIOR CONCURRENT THERAPY:

• Recovered from any effects of surgery
• Intravesicle therapy for superficial disease allowed
• Prior neoadjuvant or adjuvant chemotherapy allowed
• Must have a minimum interval of six months between the completion of neoadjuvant or adjuvant chemotherapy and the diagnosis of metastatic disease
• No prior chemotherapy for metastatic disease
• No radiotherapy within the past 4 weeks
• No drugs and herbal inducers or inhibitors of CYP3A4 (e.g., bergamottin or glabridin) within 10 days prior to study treatment and while receiving lapatinib ditosylate therapy
• No other concurrent anticancer therapy or investigational agents
• No other concurrent anticancer agents
• No concurrent treatment with other investigational therapy for other diseases or conditions
• No concurrent prophylactic antibiotics
• No concurrent prophylactic filgrastim (G-CSF)
• At least 14 days since prior and no concurrent herbal or dietary supplements
• No concurrent consumption of grapefruit juice