S0031, ZD 1839 in Treating Patients With Advanced Cancer of the Urinary Tract

RATIONALE: Biological therapies such as ZD 1839 may interfere with the growth of the tumor cells and slow the growth of cancer of the urinary tract.

PURPOSE: Phase II trial to study the effectiveness of ZD 1839 in treating patients who have advanced cancer of the urinary tract.

OBJECTIVES:

* Determine the 6-month progression-free survival rate of patients with advanced transitional cell carcinoma of the urothelium treated with ZD 1839.
* Determine the overall survival and response (confirmed complete and partial response) in these patients treated with this regimen.
* Determine the qualitative and quantitative toxicity of this regimen in these patients.
* Evaluate the changes in growth factor protein kinase expression before and after treatment and at the time of disease progression in these patients treated with this regimen.

OUTLINE: Patients receive oral ZD 1839 once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 30-55 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed transitional cell carcinoma (TCC) of the urothelium (bladder, renal pelvis, ureter, or urethra) not curable by surgery or radiotherapy

  * Any T, N0-3, M1 or unresectable M0
  * Poorly differentiated TCC, predominant TCC with rare foci of squamous differentiation, or rare foci of adenocarcinoma allowed
* Measurable disease

  * At least 1 lesion accessible for biopsy
  * Soft tissue disease that has been irradiated within the past 2 months not considered measurable disease
* Progressive or recurrent disease after only 1 prior systemic chemotherapy regimen for advanced disease
* No adenocarcinoma, small cell carcinoma, sarcoma, squamous cell carcinoma, or mixed histology

PATIENT CHARACTERISTICS:

Age:

* Any age

Performance status:

* Zubrod 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Platelet count at least 100,000/mm3
* Absolute granulocyte count at least 1,200/mm3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* SGOT no greater than 2 times ULN

Renal:

* Creatinine no greater than 2 times ULN

Other:

* No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent filgrastim (G-CSF)

Chemotherapy:

* See Disease Characteristics
* No prior adjuvant chemotherapy
* At least 28 days since prior chemotherapy and recovered

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics
* At least 28 days since prior radiotherapy and recovered

Surgery:

* See Disease Characteristics
* At least 28 days since prior surgery and recovered

Other:

* No prior systemic therapy between biopsy and study entry
* At least 28 days since prior intravesical therapy and recovered
* No concurrent agents that induce CYP3A4 (e.g., nafcillin, rifampin, carbamazepine, phenobarbital, phenytoin, or St. John's Wort)