Adjuvant Stage 2-3A Breast Cancer With Positive Lymph Nodes

A Phase II Study Of Safety And Tolerability Of Adjuvant Chemotherapy With Continuous Infusion Paclitaxel And Dose Intense Cyclophosphamide And Hematopoietic Growth Factor Support Followed By Doxorubicin For Stage II-IIIA Breast Cancer Involving Greater Than or Equal to 10 Lymph Nodes

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to damage tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with filgrastim and radiation therapy works in treating patients with stage II or stage IIIA breast cancer.

OBJECTIVES:

• Determine the feasibility of administering adjuvant paclitaxel, dose-intensive cyclophosphamide, and filgrastim (G-CSF), followed by doxorubicin and then radiotherapy in patients with stage II or IIIA breast cancer involving > 4 lymph nodes.
• Determine the incidence of febrile neutropenia in these patients during the first course of therapy.
• Compare the incidence of febrile neutropenia and duration of neutropenia in patients treated with this regimen with that seen in patients treated on protocol CWRU-4194.
• Determine the disease-free and overall survival of patients treated with this regimen.
• Evaluate the quality of life of these patients.
• Correlate HER-2/neu overexpression with disease-free and overall survival in these patients.

OUTLINE: Patients receive paclitaxel IV continuously and cyclophosphamide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until day 14 or until blood counts recover. Treatment repeats every 21 days for 3 courses. Patients then receive doxorubicin IV on day 1 and G-CSF SC on days 2-11 every 21 days for 4 courses.

Patients with hormone receptor positive disease also receive oral tamoxifen daily for 5 years beginning at the completion of chemotherapy.

Beginning 3-6 weeks after the completion of chemotherapy, patients receive radiotherapy 5 days a week for 6-7 weeks.

Quality of life is assessed days 1 and 4 of the first course of chemotherapy, day 1 of the second course, the last day of the final course, and at 6 months after the completion of treatment.

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

PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage II or IIIA breast cancer

  • At least 5 axillary lymph nodes
  • No T4 or N3 disease

• No distant metastases by CT scan of the chest, abdomen, and pelvis; bone scan; and bone marrow evaluation

• No more than 8 weeks since prior lumpectomy or mastectomy with axillary node dissection

  • Negative surgical margins

• Hormone receptor status:

  • Hormone receptor status known

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No poorly controlled ischemic heart disease or congestive heart failure

Pulmonary:

• No severe chronic obstructive or restrictive pulmonary disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No severe diabetes mellitus
• No other severe concurrent medical or psychiatric illness that would preclude study participation
• No other malignancy within past 5 years except curatively treated ductal carcinoma in situ, lobular carcinoma in situ, or breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics