Inclusion Criteria

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