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