S0353, Gemcitabine in Treating Patients With Recurrent Bladder Cancer That Has Not Responded to Previous Bacillus Calmette-Guerin

OBJECTIVES:

- Determine the 8-12 week efficacy of intravesical gemcitabine, in terms of complete
response rate, in patients with recurrent superficial transitional cell carcinoma of
the bladder that have progressed despite prior intravesical Bacillus Calmette-Guerin
(BCG).

- Determine the recurrence-free, worsening-free, progression-free, and overall survival
of patients treated with this drug.

- Evaluate the toxicity of this drug in these patients.

- Correlate, preliminarily, expression levels of genes or genetic polymorphisms involved
in the gemcitabine pathway and angiogenesis with clinical toxicity, response, and
relapse-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive gemcitabine intravesically once a week for 6 weeks
(weeks 1-6) in the absence of disease progression or unacceptable toxicity. Patients
achieving a complete response proceed to maintenance therapy at week 14.

- Maintenance therapy: Patients receive gemcitabine intravesically once in weeks 14, 18,
22, 26, 30, 34, 38, 42, 46, and 50 in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-45 patients will be accrued for this study within 6-12
months.

DISEASE CHARACTERISTICS:

- Histologically confirmed superficial transitional cell carcinoma (TCC) of the bladder
meeting 1 of the following stage criteria:

- Stage T1, grade 2-3

- Stage Tis

- Stage Ta, grade 3-4 or multifocal (> 2 lesions)

- Must have received and failed ≥ 2 courses of intravesical Bacillus Calmette-Guerin
(BCG) (one 6-week course, plus one 3-week course, or fewer weeks if BCG was
discontinued due to side effects) within the past 3 years

- Recurrent disease

- Must have had a transurethral resection of the bladder tumor (TURBT) or bladder
biopsy within the past 60 days documenting tumor recurrence and tumor stage and
grade

- TURBT or biopsy must have been performed ≥ 6 weeks after the completion of
BCG and/or other immunotherapy treatment (or ≥ 14 days after completion of
intravesical chemotherapy treatment)

- All visible tumor must have been resected at the time of the last biopsy

- No evidence of urethral or renal pelvis TCC by upper tract radiological imaging
(e.g., intravenous pyelogram, CT urogram, or retrograde pyelogram) within the past 2
years

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-2

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Not specified

Other

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No other 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 that is in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- Prior intravesical interferon alfa allowed, alone or in combination with Bacillus
Calmette-Guerin (BCG)

Chemotherapy

- See Disease Characteristics

- No more than 1 course of intravesical chemotherapy (e.g., thiotepa, mitomycin, or
doxorubicin) within the past year, defined as 6 or more weekly instillations, with or
without monthly maintenance instillations

- No prior gemcitabine

Endocrine therapy

- Not specified

Radiotherapy

- No prior pelvic radiotherapy

- No concurrent radiotherapy to any other area of the body

Surgery

- See Disease Characteristics

- Recovered from prior surgery