S0031, ZD 1839 in Treating Patients With 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.

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)