OBJECTIVES:

• Determine the overall response rate in patients with metastatic transitional cell carcinoma of the urothelium treated with cisplatin, gemcitabine, and gefitinib.
• Determine the time to progression, progression-free survival, and overall survival in patients treated with this regimen.
• Determine the effect of epidermal growth factor receptor expression level on overall response rate and progression-free survival in patients treated with this regimen.
• Determine the toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Patients also receive oral gefitinib once daily beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission, partial remission, or maintain stable disease continue oral gefitinib once daily for 5 years or until disease progression or unacceptable toxicity occurs.

Patients are followed at least every 3 months for 1 year and then at least every 6 months until disease progression or relapse.

PROJECTED ACCRUAL: A total of 12-50 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the urothelium (bladder, ureter, renal pelvis or urethra)

  • Metastatic disease (N2, N3, or M1)
  • Histologic confirmation of metastatic/recurrent disease is not required
• Not amenable to potentially curative surgery or radiotherapy

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Bladder not considered a site of measurable disease

  • Nonmeasurable lesions include:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
• No evidence of brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.25 times upper limit of normal (ULN)
• AST/ALT less than 2 times ULN
• No active severe chronic liver disease

Renal:

• Creatinine clearance greater than 50 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No pre-existing sensory or motor neuropathy greater than grade 1
• No ongoing or active infection
• No active severe chronic gastrointestinal disorders, including diarrheal or emetic disorders or malabsorptive conditions causing nausea or diarrhea
• No active severe chronic desquamative cutaneous disorders
• No active severe corneal disease or inflammatory ocular disorders
• No other concurrent active malignancy except nonmelanoma skin cancer
• HIV negative
• No psychiatric illness or social situations that would preclude compliance
• No other uncontrolled concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior systemic therapies for advanced carcinoma of the urothelium, including investigational agents targeting the HER2/neu, signal transduction, angiogenic, immune, and cell cycle pathways
• No concurrent immunotherapy

Chemotherapy:

• No prior systemic chemotherapy except single-agent chemotherapy used as a radiosensitizer
• No prior adjuvant or neoadjuvant chemotherapy
• Prior intravesical chemotherapy allowed
• More than 4 weeks since prior intravesical chemotherapy and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• More than 7 days since prior dexamethasone

• No concurrent hormonal therapy except:

  • Steroids for adrenal failure
  • Hormones for nondisease-related conditions (e.g., insulin for diabetes)
  • Intermittent use of dexamethasone as an antiemetic

Radiotherapy:

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy, including palliative radiotherapy

Surgery:

• More than 4 weeks since prior major surgery and recovered

Other:

• No prior gefitinib
• No prior investigational epidermal growth factor receptors for advanced carcinoma of the urothelium
• More than 7 days since prior CYP3A4 inducers, including phenytoin, carbamazepine, barbiturates, rifampin, Hypericum perforatum, modafinil, or rifapentine
• No concurrent CYP3A4 inducers, including phenytoin, carbamazepine, barbiturates, rifampin, Hypericum perforatum, modafinil, or rifapentine
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational therapy