Paclitaxel or Docetaxel in Treating Women With Advanced Breast Cancer

OBJECTIVES:

• Compare the response rate in women with metastatic or locally advanced, inoperable adenocarcinoma of the breast treated with docetaxel vs paclitaxel.
• Compare the toxicity of these regimens in these patients.
• Compare the time to disease progression, duration of response, quality of life, and survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive paclitaxel IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and after courses 4 and 6.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 400 patients (200 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven metastatic or locally advanced, inoperable adenocarcinoma of the breast

• Clinically evident metastases (e.g., clearly malignant lesions on chest x-ray or CT or abdominal CT do not require histologic confirmation)
• Hot spots on bone scan not shown to be malignant on plain x-rays are not adequate evidence of malignant disease in the absence of other lesions
• Must meet 1 of the following conditions:

• Disease progression after 1 prior chemotherapy regimen for locally advanced or metastatic disease (which may or may not have followed a separate adjuvant regimen using chemotherapy or hormonal therapy)
• Locally advanced or metastatic disease during or after 1 adjuvant or neoadjuvant chemotherapy regimen
• One of the above chemotherapy regimens must have contained an anthracycline (e.g., doxorubicin, but not mitoxantrone)
• Single drug substitution (e.g., methotrexate for doxorubicin) during prior combination chemotherapy allowed
• Bidimensionally measurable
• No clinical or radiographic evidence of brain or leptomeningeal disease
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Karnofsky 60-100% OR
• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin normal
• SGOT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• No uncontrolled hypercalcemia

Cardiovascular:

• No myocardial infarction within the past 6 months
• No history of arrhythmia requiring treatment
• No heart block
• No clinical evidence of congestive heart failure
• No unstable angina (e.g., new onset, crescendo, or rest angina)
• Stable exertional angina allowed

Other:

• No current symptomatic grade 2 or greater peripheral neuropathy
• No history of hypersensitivity to products containing Cremophor EL (e.g., cyclosporine or teniposide) or Polysorbate 80 (e.g., IV etoposide)
• No serious infection
• No significant psychiatric disease that would preclude study
• No other malignancy within the past 5 years except nonmelanomatous skin cancer or completely excised carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow or stem cell transplantation

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (2 weeks for oral cyclophosphamide or 6 weeks for nitrosoureas or mitomycin)
• No prior high-dose chemotherapy given with ablative intent
• No prior taxoids
• No other concurrent antineoplastic therapy

Endocrine therapy:

• See Disease Characteristics
• Prior hormonal therapy as adjuvant therapy or for metastatic disease allowed
• At least 1 week since prior hormonal therapy
• No concurrent corticosteroids except:

• Prophylaxis or treatment for acute hypersensitivity reactions
• Chronic therapy (more than 6 months) at low doses (20 mg/day or less of methylprednisolone or equivalent)

Radiotherapy:

• At least 4 weeks since prior radiotherapy to major bone marrow areas
• No prior high-dose radiotherapy given with ablative intent
• No concurrent radiotherapy except limited palliative radiotherapy (e.g., for a solitary rib fracture) during objective response

Surgery:

• See Disease Characteristics
• More than 2 weeks since prior surgery except simple biopsy or placement of venous access device

Other:

• At least 4 weeks since prior investigational drugs
• Concurrent medications known to alter cardiac conduction (e.g., digoxin, beta blockers, or calcium channel blockers) allowed
• No concurrent ketoconazole
• No concurrent bisphosphonates unless initiated more than 3 months before randomization
• No concurrent experimental drug or therapy