Combination Chemotherapy and Trastuzumab in Treating Women With Metastatic Breast Cancer

OBJECTIVES:

• Compare the response rate associated with two different treatment schedules of paclitaxel, carboplatin, and trastuzumab (Herceptin) in women with overexpressed HER-2 growth factor receptor and metastatic breast cancer. (Schedule A closed to accrual effective 05/16/2003).
• Compare the time to progression and median survival in patients treated with these schedules.
• Compare the toxicity of these treatment schedules in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior adjuvant therapy (none vs less than 6 months vs at least 6 months), estrogen receptor (ER) status and progesterone receptor (PR) status at initial diagnosis (ER positive/PR positive or unknown vs ER positive/PR negative vs ER positive or unknown/PR negative), menopausal status (pre vs post), and performance status (0 or 1 vs 2). Patients are assigned to 1 of 2 treatment schedules.

• Schedule A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes and then trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression. (Schedule A closed to accrual effective 05/16/2003).
• Schedule B: Patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 15 minutes on day 1 of weeks 1-3 and trastuzumab IV over 90 minutes immediately after carboplatin on day 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 36-92 patients (18-46 per treatment schedule) will be accrued for this study within 7-18.5 months. (Schedule A closed to accrual effective 05/16/2003).

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic adenocarcinoma of the breast
• Strong overexpression of HER-2 by immunohistochemistry (3+)

• 0-2+ tumors allowed if demonstrate amplification by FISH
• Bidimensionally measurable disease
• Brain metastasis must not represent sole site of disease
• No untreated brain metastasis receiving radiotherapy
• Previously treated brain metastases in continued response to radiotherapy and/or surgery for at least 2 months allowed
• Hormone receptor status:

• Positive or negative

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure or unstable angina
• No clinically significant pericardial effusion or arrhythmia

Other:

• No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No active uncontrolled infection
• No prior allergic reaction to Cremophor EL, anesthetics, or muscle relaxants
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF)

Chemotherapy:

• Prior adjuvant chemotherapy allowed
• Prior taxane therapy allowed
• No prior cisplatin or carboplatin
• No prior chemotherapy for metastatic disease

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to more than 25% of marrow
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior surgery and recovered

Other:

• At least 7 days since prior parenteral antibiotics