Fenretinide in Treating Patients Who Have Undergone Surgery for Bladder Cancer

OBJECTIVES:

- Determine the efficacy, mechanism of action, and toxicity of fenretinide in patients at
risk of recurrent superficial bladder cancer after complete resection of initial tumor.

- Determine the treatment effects in modulating the expression of retinoid receptors,
chromosomal abnormalities (numerical chromosomal abnormalities and DNA ploidy),
apoptosis, and autocrine motility factor receptor (intermediate endpoint markers of
recurrent disease) in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lesion
type (multifocal vs solitary). Patients are randomized to one of two treatment arms.

Patients receive either oral fenretinide or placebo on days 1-25. Courses repeat every 28
days for up to 1 year in the absence of disease progression, unacceptable toxicity, or
development of a second primary cancer requiring therapy.

Patients are followed every 3 months for 15 months.

PROJECTED ACCRUAL: A total of 178 patients (89 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically proven solitary or multifocal superficial (stage Ta, grades 1-2)
transitional cell carcinoma (TCC) of the bladder meeting 1 of the following criteria:

- Newly diagnosed and no more than 4 weeks since resection

- Secondary after being tumor free (including carcinoma in situ) for more than 12
months with no intravesical therapy within that 12 months OR

- Histologically proven Ta, T1, or Tis TCC of the bladder previously treated with
Bacillus Calmette-Guerin (BCG).

- Must have received 6 weeks of induction BCG followed by no evidence of disease by
cystoscopy and cytology and then further treatment with 3 weekly doses of BCG.

- Visible tumor totally resected within 4 weeks prior to study entry and no further
surgery, intravesical therapy, or systemic therapy planned

- No prostatic, prostatic urethral, or upper tract TCC involvement by the index tumor at
resection

- No metastatic disease

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Zubrod (Eastern Cooperative Oncology Group (ECOG)) 0-2

Life expectancy:

- At least 2 years

Hematopoietic:

- white blood count (WBC) greater than 3,000/mm^3

- Platelet count greater than 100,000/mm^3

- Hemoglobin greater than 11.0 g/dL

Hepatic:

- serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase
(SGPT) less than 1.5 times upper limit of normal (ULN)

Renal:

- Creatinine less than 2.0 mg/dL

Other:

- Triglyceride level less than 2.5 times ULN

- No other concurrent malignancy except nonmelanomatous skin cancer

- No other malignancy within the past 5 years unless currently disease free, at least 6
months since prior therapy, no current or planned active therapy, and expected
disease-free survival at least 2 years

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 1 year after the
study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- No concurrent systemic biologic therapy

Chemotherapy:

- See Disease Characteristics

- No prior systemic cytotoxic chemotherapy for bladder cancer

- At least 1 year since prior cytotoxic chemotherapy for nonbladder cancer

- No concurrent systemic chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- No prior radiotherapy to the bladder

- No concurrent radiotherapy

Surgery:

- See Disease Characteristics

Other:

- At least 3 months since prior high-dose vitamin A (greater than 25,000 IU) or beta
carotene (at least 30 mg/day)

- At least 3 months since prior retinoid therapy