RATIONALE: Biological therapies use different ways to stimulate the immune system and stop
cancer cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells
from dividing so they stop growing or die. It is not yet known whether keyhole limpet
hemocyanin is more effective than doxorubicin for bladder cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of keyhole limpet
hemocyanin with that of doxorubicin in treating patients who have bladder cancer that has
not responded to BCG or in those patients who cannot tolerate BCG.
- 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
- 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
- 18 and over
- ECOG 0-2 OR
- Karnofsky 60-100%
- Not specified
- WBC greater than 4,000/mm^3
- Platelet count greater than 100,000/mm^3
- Hemoglobin greater than 11 g/dL
- Bilirubin normal
- SGOT/SGPT normal
- Creatinine no greater than 1.5 times upper limit of normal
- No severe cardiovascular disease
- 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:
- See Disease Characteristics
- No prior keyhole limpet hemocyanin immune activator
- No prior doxorubicin
- At least 3 months since prior mitomycin
- No other concurrent chemotherapy
- No concurrent steroids
- At least 4 months since prior radiotherapy
- See Disease Characteristics
- At least 4 weeks since prior intravesical therapy
- At least 3 months since prior investigational agents
- No concurrent cytotoxic immunosuppressive agents