• To determine the safety of administering continuous infusion paclitaxel with dose intense cyclophosphamide [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
  Paclitaxel 160 mg/m2 given over 72 hours by continuous infusion days 1-3 given concurrently with cyclophosphamide 700 mg/m2 daily for 3 day every 3 weeks cycles 1-3. Patients will be observed in the outpatient treatment area during the first 2 hours of the paclitaxel infusion for allergic reactions. Epinephrine, hydrocortisone, and IV antihistamine will be available.
  
  
• To determine the incidence of febrile neutropenia with the first cycle of therapy. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  A specific objective of this trial is to estimate the incidence of febrile neutropenia. The observed incidence of febrile neutropenia with the first cycle of cyclophosphamide and paclitaxel, as well as the observed number of days of grade ¾ neutropenia during the first treatment cycle, will be reported along with 95% confidence intervals.
  
  

Biological: filgrastim
Neupogen (G-CSF) given at a dose of 10 ugm/kg subcutaneously starting on day 5 and continuing until ANC > 10,000/uL x1 day after the nadir cycles 1-3.
Other Names:
• G-CSF, Neupogen®
• recominant-methionyl human granulocyte-colony stimulating factor
• granulocyte colony stimulating factor
• r-methHuG-CSF
Drug: cyclophosphamide
cyclophosphamide 700 mg/m2 daily for 3 day every 3 weeks cycles 1-3
Other Names:
• Cytoxan®
• CTX
• CPM
• Neosar®
Drug: doxorubicin hydrochloride
Patients then receive doxorubicin IV on day 1.
Drug: paclitaxel
Paclitaxel 160 mg/m2 given over 72 hours by continuous infusion days 1-3
Other Name: Taxol®
Drug: tamoxifen citrate
tamoxifen at a dose of 20 mg daily for 5 years after chemotherapy is completed
Procedure: adjuvant therapy
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.
Radiation: radiation therapy
Beginning 3-6 weeks after the completion of chemotherapy, patients receive radiotherapy 5 days a week for 6-7 weeks.

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.

Treatment continues in the absence of disease progression or unacceptable toxicity.

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.