Phase II trial to study the effectiveness of irofulven in treating patients who have
metastatic breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells
from dividing so they stop growing or die.
I. Evaluate the response rate and time to treatment failure in patients with refractory
metastatic adenocarcinoma of the breast treated with irofulven.
II. Assess the qualitative and quantitative toxic effects of this drug in these patients.
III. Determine the population pharmacokinetics and the pharmacokinetics-pharmacodynamic
relationships of this drug in these patients.
OUTLINE: This is a multicenter study.
Patients receive irofulven IV over 30 minutes on days 1 and 15. Treatment continues every 28
days in the absence of disease progression or unacceptable toxicity.
- Histologically confirmed metastatic adenocarcinoma of the breast
- Measurable disease outside previously irradiated area or occurred/progressed after
completion of radiotherapy
- Must have received 1 or 2 prior chemotherapy regimens for metastatic disease
- More than 3 prior regimens allowed
- No active brain metastases or meningeal breast cancer involvement
- Male or female
- SWOG 0-2
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- SGOT or SGPT no greater than 3 times ULN (5 times ULN for liver metastases)
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
- No history of myocardial infarction or unstable angina within the past 6 months
- No uncontrolled congestive heart failure
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Prior diagnosis of cancer allowed (must be off cancer therapy and have no evidence of
- No history of retinopathy and/or macular degeneration
PRIOR CONCURRENT THERAPY:
- No prior irofulven