RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells. Drugs
such as mesna may be effective in preventing some of the side effects of chemotherapy.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy consisting of
etoposide and ifosfamide given with mesna, and cisplatin in treating patients who have
metastatic breast cancer.
- 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
Patients are followed every 3 months.
PROJECTED ACCRUAL: At least 36 patients (16 per stratum) will be accrued over 36 months.
- 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
- Not specified
- Not specified
- ECOG 0-2
- At least 3 months
- Hemoglobin at least 10 g/dL
- WBC at least 4,000/mm3
- Platelet count at least 100,000/mm3
- Bilirubin no greater than 2.0 mg/dL
- Creatinine no greater than 1.5 mg/dL
- No bladder outlet obstruction
- No symptomatic cardiovascular disease (e.g., congestive heart disease) or inability
to tolerate a fluid load
- 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:
- No greater than 1 prior biologic response modifier treatment for metastatic disease
- 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
- Prior medical or surgical hormonal therapy allowed
- 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
- Recovered from effects of major surgery
- At least 7 days since prior nephrotoxic drugs (e.g., aminoglycosides, diuretics,
lithium, intravenous contrast, or nonsteroidal antiinflammatory drugs)
Scot C. Remick, MD
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center