epirubicin, docetaxel, and pegfilgrastim in treating women with locally advanced or inflammatory breast cancer

Conditions: Breast Cancer

Summary: 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

Keywords: stage iiia breast cancer stage iiib breast cancer stage iiic breast cancer inflammatory breast cancer