Epirubicin, Docetaxel, and Pegfilgrastim in Treating Women With Locally Advanced or Inflammatory Breast Cancer

RATIONALE: Drugs used in chemotherapy such as epirubicin and docetaxel use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as pegfilgrastim 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.

PURPOSE: Phase I/II trial to study the effectiveness of combining epirubicin and docetaxel with pegfilgrastim in treating women who have locally advanced or inflammatory breast cancer.

OBJECTIVES:

* Determine the maximum tolerated dose and recommended phase II dose of docetaxel and epirubicin when given with pegfilgrastim in women with locally advanced or inflammatory breast cancer. (Phase I, group 1 closed to accrual as of 9/13/04 and Phase II, group 1 closed to accrual as of 5/10/06)
* Determine the toxicity of this regimen in these patients.
* Determine the clinical and pathological response rate and duration of response in patients treated with this regimen.
* Determine drug sensitivity and resistance in patients treated with this regimen.
* Determine prognostic and predictive markers in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter, dose-escalation study of docetaxel and epirubicin.

* Phase I:

Group 1 (21-day regimen) (closed to accrual as of 09/13/04): Patients receive epirubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with objective response after 6 courses may receive additional therapy at the discretion of the physician.

Group 2 (14-day regimen): Patients receive epirubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with objective response after 8 courses may receive additional therapy at the discretion of the physician.

Cohorts of 3-6 patients receive escalating doses of epirubicin and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Phase II:

Group 1 (21-day regimen) (closed to accrual as of 5/10/06): Patients receive treatment as in phase I with epirubicin and docetaxel at the recommended Phase II dose.

Group 2 (14-day regimen): Patients receive treatment as in phase I with epirubicin and docetaxel at the recommended Phase II dose.

Patients are followed at 1 month, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 90 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed invasive adenocarcinoma of the breast, meeting any of the following criteria:

  * T4, NX, M0
  * Any T, N2-N3, M0
  * Inflammatory breast cancer (redness over at least one-third of the breast), M0
* No evidence of metastatic disease by chest x-ray, abdominal ultrasound or CT scan and bone scan
* Diagnosed within the past 8 weeks
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age

* 16 and over

Sex

* Female

Menopausal status

* Not specified

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute granulocyte count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic

* Bilirubin less than upper limit of normal (ULN)
* Must meet criteria for 1 of the following:

  * ALT and AST no greater than 1.5 times ULN AND alkaline phosphatase no greater than 2.5 times ULN
  * ALT and AST normal AND alkaline phosphatase no greater than 5 times ULN

Renal

* Creatinine no greater than 1.5 times ULN

Cardiovascular

* Resting LVEF normal by MUGA or echocardiogram
* No congestive heart failure
* No angina pectoris
* No myocardial infarction within the past year
* No uncontrolled hypertension
* No uncontrolled arrhythmias

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective non-hormonal contraception
* No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
* No symptomatic peripheral neuropathy grade 2 or greater
* No active infection
* No history of significant neurological or psychiatric disorders, including dementia or seizures
* No peptic ulcer
* No unstable diabetes mellitus
* No contraindication to dexamethasone
* No known sensitivity to E. coli-derived or polyethylene glycol products
* Willing to undergo core biopsies once prior to registration and core biopsies at 2 other timepoints while on study
* Geographically accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior immunotherapy for breast cancer

Chemotherapy

* No prior chemotherapy for breast cancer

Endocrine therapy

* No prior hormonal therapy for breast cancer
* No concurrent corticosteroids except for premedication or hypersensitivity reaction
* No concurrent oral contraception

Radiotherapy

* No prior radiotherapy for breast cancer

Surgery

* No prior surgery for breast cancer other than biopsy

Other

* No prior systemic therapy for breast cancer
* No other concurrent investigational drugs or anticancer treatment
* No concurrent preventative IV antibiotics