Inclusion Criteria:
- Histologically or cytologically confirmed breast cancer
- Metastatic disease
- Measurable disease
- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
OR ≥ 10 mm by spiral CT scan
- The following are not considered measurable disease:
- Bone disease only
- Pleural effusion
- Peritoneal effusion
- Must have received prior anthracycline (doxorubicin or epirubicin) and/or taxane
(paclitaxel or docetaxel) as adjuvant therapy or for advanced disease
- Therapy with high-dose regimens or bone marrow transplantation is considered 1
prior regimen
- No known brain metastases
- Hormone receptor status:
- Not specified
- Male or female
- Performance status - ECOG 0-1
- Performance status - Karnofsky 70-100%
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- WBC ≥ 3,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin normal
- AST or ALT ≤ 2.5 times upper limit of normal
- Creatinine normal
- Creatinine clearance ≥ 60 mL/min
- QTc < 500 msec
- No New York Heart Association class III or IV congestive heart failure
- No myocardial infarction within the past year
- No uncontrolled dysrhythmia
- No poorly controlled angina
- No other significant cardiac disease
- No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular
fibrillation ≥ 3 beats in a row)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to FR901228
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No concurrent biologic agents
- No more than 1 prior chemotherapy regimen for metastatic disease
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered
- No prior FR901228 (depsipeptide)
- No other concurrent chemotherapy
- Prior hormonal therapy for metastatic disease or as adjuvant therapy allowed
- More than 4 weeks since prior radiotherapy and recovered
- No concurrent radiotherapy
- More than 2 weeks since prior minor surgery and recovered
- More than 4 weeks since prior major surgery and recovered
- Concurrent bisphosphonates allowed provided therapy was initiated ≥ 3 months ago
- No concurrent agents that cause QTc prolongation
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent drugs known to have histone deacetylase activity (e.g., valproic acid)
- No other concurrent investigational agents
- No other concurrent anticancer therapy