SU5416 and Doxorubicin in Treating Patients With Stage IIIB or Stage IV Inflammatory Breast Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer.
• Determine the overall response, response rate, and progression-free survival rate of patients treated with this regimen.
• Determine the antiangiogenic effects of this regimen in these patients.
• Assess the relationship of plasma levels of these drugs with safety and efficacy in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive doxorubicin IV continuously over 72 hours on days 1-3 of course 1. For all subsequent courses, patients receive doxorubicin as in course 1 and SU5416 IV over 1 hour twice weekly (on days 1 and 4) beginning on week 2 of course 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. After chemotherapy, all patients undergo a modified radical mastectomy and radiotherapy to the chest wall and regional lymph nodes. Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy.

Cohorts of 3-6 patients receive escalating doses of SU5416 and doxorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 3 patients may be treated at that dose level.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 6-9 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed stage IIIB or IV (supraclavicular lymph node involvement or metastasis) inflammatory breast cancer

• Primary or secondary
• No brain metastases or primary brain tumors
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,500/mm^3
• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 9.0 g/dL

Hepatic:

• Bilirubin normal
• AST and ALT less than 2 times upper limit of normal
• PT and PTT normal OR
• INR less than 1.1

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• LVEF at least 50% by MUGA
• No New York Heart Association class III or IV heart disease
• No uncompensated coronary artery disease
• No myocardial infarction or unstable angina within the past 6 months
• No deep venous or arterial thrombosis within the past 3 months

Pulmonary:

• No history of pulmonary embolism within the past 3 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of diabetes mellitus with severe peripheral vascular disease
• No other prior or concurrent malignancies within the past 10 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No other uncontrolled illnesses

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent epoetin alfa or filgrastim (G-CSF)

Chemotherapy:

• No more than 2 prior chemotherapy regimens allowed
• No prior doxorubicin or other anthracycline

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy allowed

Surgery:

• Not specified