OBJECTIVES:

• Determine the objective response rate in patients with metastatic breast cancer treated with etoposide, ifosfamide with mesna, and cisplatin.
• Determine the tolerability and toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to number of prior chemotherapy courses for metastatic disease (0 vs 1).

Patients receive etoposide IV over 60-90 minutes, cisplatin IV over 30 minutes, and ifosfamide IV over 30 minutes on days 1-3. Mesna is administered IV over 15 minutes 30 minutes prior to and 4 hours after ifosfamide, then orally at 8 hours post infusion. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months.

PROJECTED ACCRUAL: At least 36 patients (16 per stratum) will be accrued over 36 months.

DISEASE CHARACTERISTICS:

• Histologically proven progressive metastatic breast cancer

• Measurable disease

  • Any lesion measurable in 2 dimensions
  • Hepatic metastases if the sum of the measurements below the costal margin in the midclavicular line and the tip to the xiphoid process is greater than 5 cm during quiet respiration
  • Hepatic defects that are clearly measurable by radionuclide, CAT, or MRI scans
  • Bone metastases are not considered measurable disease
  • Evaluable disease allowed if measurable disease also present
• No brain metastases, carcinomatous meningitis, or spinal cord compression

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• Not specified

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Hemoglobin at least 10 g/dL
• WBC at least 4,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL
• No bladder outlet obstruction

Cardiovascular:

• No symptomatic cardiovascular disease (e.g., congestive heart disease) or inability to tolerate a fluid load

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No prior malignancies except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No greater than 1 prior biologic response modifier treatment for metastatic disease

Chemotherapy:

• No greater than 1 prior chemotherapy regimen for metastatic disease allowed
• Patients who relapsed during or within 6 months after adjuvant chemotherapy are considered to have failed 1 regimen
• Patients who relapsed more than 6 months after adjuvant chemotherapy are considered to not have had a prior regimen
• Greater than 4 weeks since prior chemotherapy (greater than 6 weeks for mitomycin or nitrosoureas) and recovered
• No prior cisplatin, etoposide, or ifosfamide

Endocrine therapy:

• Prior medical or surgical hormonal therapy allowed

Radiotherapy:

• Prior radiation therapy to areas of measurable disease allowed if indicator lesion increased in size by greater than 25% after treatment
• Recovered from effects of prior radiotherapy

Surgery:

• Recovered from effects of major surgery

Other:

• At least 7 days since prior nephrotoxic drugs (e.g., aminoglycosides, diuretics, lithium, intravenous contrast, or nonsteroidal antiinflammatory drugs)