OBJECTIVES:

• Compare the efficacy of BCI-ImmuneActivator™ (keyhole limpet hemocyanin) versus doxorubicin in BCG refractory or intolerant patients with carcinoma in situ with or without resected superficial papillary bladder cancer.
• Compare the toxicity and safety of these treatments in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and prior BCG response (refractory vs intolerant). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive a sensitizing dose of keyhole limpet hemocyanin (KLH) intradermally at week -2 followed by induction KLH IV once weekly at weeks 1-6. Patients with partial or no response receive IV KLH reinduction therapy once weekly at weeks 13-18. Patients with complete response receive IV KLH maintenance therapy monthly at weeks 13, 17, and 21, and then at months 6-12.
• Arm II: Patients receive doxorubicin IV once weekly at weeks 1-6. Patients with complete response receive maintenance therapy comprising doxorubicin IV at weeks 13, 17, and 21 and months 6-12.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1.5 years, and then every 6 months for 1 year. (Patient total participation in this study may last as long as 42 months.)

PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed carcinoma in situ of the bladder with or without resected superficial papillary tumor

  • Biopsy within 3 months of study with or without positive urinary cytology within 6 weeks of study
• Cystoscopy within 3 months of study
• Negative imaging study of the ureters and kidneys within 6 months of study

• BCG refractory disease

  • Received and failed at least 1 prior induction course consisting of BCG weekly for 6 weeks OR

• BCG intolerant

  • Unable to receive an adequate course of intravesical BCG due to extreme toxicity
• Opted against or medically contraindicated to cystectomy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 4,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 11 g/dL

Hepatic

• Bilirubin normal
• SGOT/SGPT normal

Renal

• Creatinine no greater than 1.5 times upper limit of normal

Cardiovascular

• No severe cardiovascular disease

Other

• No other severe disease
• No other malignancy within the past 5 years except basal or squamous cell skin cancer or noninvasive cancer of the cervix
• No evidence of autoimmune disease, known immune deficiency, or immunosuppression
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior keyhole limpet hemocyanin immune activator

Chemotherapy

• No prior doxorubicin
• At least 3 months since prior mitomycin
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent steroids

Radiotherapy

• At least 4 months since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 4 weeks since prior intravesical therapy
• At least 3 months since prior investigational agents
• No concurrent cytotoxic immunosuppressive agents