RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of bryostatin 1 in treating patients with
stage IV breast cancer.
- Determine the clinical response of patients with stage IV breast cancer to bryostatin
- Determine the efficacy of this regimen in these patients.
- Estimate the pharmacokinetic parameters of bryostatin 1 when given as 24 hour infusion.
- Determine the ability of this regimen to regulate lymphocyte function in these
- Determine the effect of this regimen on platelet function and protein kinase C activity
in these patients.
OUTLINE: Patients receive bryostatin 1 IV over 24 hours. Treatment continues weekly in the
absence of disease progression or unacceptable toxicity.
Patients are followed every 4-8 weeks for tumor response.
PROJECTED ACCRUAL: A total of 14-25 patients will be accrued for this study.
- Unequivocal diagnosis of metastatic breast cancer
- Bidimensionally measurable disease
- No uncontrolled CNS metastases
- No disease that is evaluable only, including blastic bone disease, malignant ascites,
and malignant pleural effusion
- Hormone receptor status:
- Not specified
- 18 and over
- Not specified
- SWOG 0-2 OR
- Karnofsky 60-100%
- At least 18 weeks
- Platelet count at least 50,000/mm^3
- PT and PTT within normal limits
- Neutrophil count at least 2,000/mm^3
- Bilirubin no greater than 1.2 mg/dL
- Transaminases no greater than 3 times normal
- Creatinine no greater than 1.6 mg/dL OR
- Creatinine clearance at least 70 mL/min
- No active infections requiring antibiotics
- No viral hepatitis allowed
- Seronegative for hepatitis B or C
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 2 months following
PRIOR CONCURRENT THERAPY:
- No concurrent immunotherapy
- 2 prior chemotherapy regimens for metastatic disease allowed as adjuvant therapy or
for advanced disease (may include high dose chemotherapy with stem cell support)
- At least 4 weeks since prior chemotherapy
- At least 6 weeks since prior nitrosourea or mitomycin therapy
- No other concurrent chemotherapy
- 2 prior hormonal therapy regimens for metastatic disease as adjuvant therapy or for
advanced diseases allowed
- At least 2 weeks since prior hormonal therapy (at least 4 weeks in case of disease
progression while receiving hormonal therapy after initial response)
- No concurrent hormonal therapy except oral contraceptives
- No concurrent use of steroids except for management of severe or life- threatening
toxic effects arising from bryostatin 1
- At least 2 weeks since prior radiotherapy
- No concurrent radiotherapy
- Not specified
- No concurrent use of drugs known to interfere with platelet function, such as aspirin
or NSAIDs (including ibuprofen)
- No concurrent use of anticoagulants
- At least 2 weeks since prior use of aspirin
- At least 2 days since prior use of NSAIDS
- Concurrent use of acetaminophen to control pain is allowed
- If acetaminophen inadequate for pain control, concurrent use of oral narcotics such
as codeine or oxycodone is allowed