BCG With or Without Gefitinib in Treating Patients With High-Risk Bladder Cancer

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed transitional cell carcinoma (TCC) of the bladder meeting ≥ 1 of the following criteria:
• •* Noninvasive papillary carcinoma (Ta) with ≥ 1 of the following characteristics:
• •* Recurrence of bladder tumor(s) ≥ grade 2 within 6 months after transurethral resection (TUR)
• •* Three or more bladder tumors ≥ grade 2 at the time of TUR
• •* Bladder tumor(s) ≥ 5 cm in size and ≥ grade 2 at the time of TUR
• •* Any grade 3 bladder tumor(s)
• •* Carcinoma in situ (Tis)
• •* At least grade 2 tumor that invades the subepithelial connective tissue (T1)
• •Has undergone TUR of all visible bladder lesions within the past 21 to 60 days with biopsy of the underlying bladder wall for all tumors and cold-cup biopsy of all suspicious areas
• •No metastatic disease as confirmed by negative radiology within the past 16 weeks, including the following:
• •* Chest x-ray
• •* Imaging of the upper urinary tract by 1 of the following methods:
• •* CT scan, MRI, or ultrasound of the abdomen and pelvis
• •* Intravenous pyelogram
• •* Retrograde pyelogram
• •No evidence of TCC of the upper urinary tract
• •No mixed histology of bladder cancer (i.e., TCC and squamous cell carcinoma of the bladder or TCC and small cell carcinoma of the bladder) at the most recent TUR
• •PATIENT CHARACTERISTICS:
• •ECOG performance status 0-2
• •Life expectancy \> 5 years
• •Negative routine urine microscopy and negative urine culture within the past 14 days
• •Willing to complete quality of life questionnaires in English or French
• •* Inability to complete questionnaires due to illiteracy in English or French, loss of sight, or other reason allowed
• •WBC ≥ 3,000/mm³
• •Absolute neutrophil count ≥ 1,500/mm³
• •Platelet count ≥ 100,000/mm³
• •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• •AST and ALT ≤ 1.5 times ULN
• •Alkaline phosphatase ≤ 1.5 times ULN
• •Creatinine ≤ 1.5 times ULN
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception during and for 3 months after study completion
• •No significant history of cardiac disease including, but not limited to, any of the following:
• •* Uncontrolled high blood pressure
• •* Unstable angina
• •* Congestive heart failure
• •* Myocardial infarction within the past year
• •* Cardiac ventricular arrhythmias requiring medication
• •No active urinary tract infection
• •No active infection, including tuberculosis
• •No serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment
• •No febrile illness or gross hematuria
• •No impaired immune response from any cause (congenital, therapy, or disease)
• •No clinically significant or untreated ophthalmologic condition (e.g., Sjögren's syndrome)
• •No gastrointestinal conditions (e.g., Crohn's disease or ulcerative colitis)
• •No history of psychiatric or neurological disorder that would limit study compliance
• •No other malignancies except for adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
• •No contraindications to spinal or general anesthesia as required for a TUR
• •No known hypersensitivity to BCG or gefitinib
• •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs
• •PRIOR CONCURRENT THERAPY:
• •See Disease Characteristics
• •More than 12 months since prior intravesical immunotherapy (including BCG +/- interferon)
• •More than 6 months since prior intravesical chemotherapy (including mitomycin C, thiotepa, doxorubicin hydrochloride)
• •* Single dose of intravesical mitomycin C at the time of the most recent TUR (within the past 21 to 60 days) allowed if considered standard care
• •No other prior or concurrent immune modulator therapy
• •No prior pelvic radiation
• •No prior gefitinib
• •No other concurrent experimental anticancer drugs
• •No concurrent use of drugs that induce CYP3A4 enzymes that have been shown to significantly reduce plasma concentrations of gefitinib (including phenytoin, carbamazepine, barbiturates, rifampin, or Hypericum perforatum \[St. John's wort\])
• •No concurrent grapefruit juice