combination chemotherapy in treating patients with high-risk breast cancer

Conditions: Breast Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: this randomized phase ii trial is studying two different regimens of combination chemotherapy and comparing them to see how well they work in treating patients with high-risk primary stage ii or stage iii breast cancer.

objectives: * compare the toxic effects of doxorubicin, cyclophosphamide, and paclitaxel vs cyclophosphamide, thiotepa, and carboplatin in patients with high-risk primary breast cancer. (arm i closed to accural as of 4/6/2006.) * compare the efficacies of these regimens followed by peripheral blood stem cell rescue in these patients. * determine the efficacy of a bisphosphonate to prevent relapse/metastasis after high-dose chemotherapy in these patients. outline: this is a randomized study. patients are stratified by stage of disease. peripheral blood stem cells (pbsc) are collected after mobilization with filgrastim (g-csf), administered subcutaneously or iv, twice daily beginning 3 days before collection and continuing until collection is complete. all patients receive conventional-dose adjuvant chemotherapy, probably comprising doxorubicin iv, cyclophosphamide iv, and fluorouracil iv over 1 hour on days 1, 22, 43, and 64. patients are then randomized to receive 1 of 2 treatment arms of high-dose chemotherapy. (arm i closed to accrual as of 4/6/2006.) * arm i (act) (closed to accrual as of 4/6/2006): patients receive doxorubicin iv over 24 hours on days -9 to -6, cyclophosphamide iv over 2 hours on day -5, and paclitaxel iv over 24 hours on day -2. pbsc are reinfused on days -2 and 0. g-csf is administered beginning on day 0 and continuing until blood counts recover. * arm ii (stamp v): patients receive cyclophosphamide iv, carboplatin iv, and thiotepa iv over 24 hours on days -7 to -4. pbsc are reinfused and g-csf is administered as in arm i. within 4-6 weeks of day 0 of high-dose chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen twice daily for 5 years. patients are also randomized to receive a bisphosphonate comprising pamidronate iv every 4 weeks for 2 years. quality of life is assessed before therapy, at 30 days after high-dose chemotherapy, and at 6 and 12 months. patients are followed every 3 months for 1 year and then every 6 months for at least 10 years. projected accrual: a total of 100 patients will be accrued for this study within 3 years.

Eligibility criteria:
disease characteristics: * histologically proven high-risk primary breast cancer with less than 60% chance of progression-free survival of 3 years from diagnosis * stage ii with at least 10 positive axillary nodes or * stage iiia or iiib * no histologically proven bone marrow metastasis * no cns metastasis * hormone receptor status: * hormone receptor status known patient characteristics: age: * physiological age 60 or under menopausal status: * not specified performance status: * karnofsky 80-100% life expectancy: * see disease characteristics hematopoietic: * neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl * sgot or sgpt no greater than 2 times upper limit of normal * hepatitis b antigen negative renal: * creatinine no greater than 1.2 mg/dl * creatinine clearance at least 70 ml/min * no prior hemorrhagic cystitis cardiovascular: * ejection fraction at least 55% by muga * no prior significant valvular heart disease or arrhythmia pulmonary: * fev_1 at least 60% of predicted * po_2 at least 85 mm hg on room air * pco_2 at least 43 mm hg on room air * dlco at least 60% lower limit of predicted other: * no other prior malignancy except squamous cell or basal cell skin cancer or stage i or carcinoma in situ of the cervix * no cns dysfunction that would preclude compliance * hiv negative * no sensitivity to e. coli-derived products * not pregnant * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * not specified chemotherapy: * at least 4 weeks since prior chemotherapy * no prior doxorubicin of total dose exceeding 240 mg/m\^2 * no prior paclitaxel of total dose of at least 750 mg/m\^2 * no more than 12 months since prior conventional-dose adjuvant chemotherapy endocrine therapy: * at least 4 weeks since prior hormonal therapy radiotherapy: * at least 4 weeks since prior radiotherapy * no prior radiation to the left chest wall surgery: * not specified

Keywords: stage ii breast cancer stage iiia breast cancer stage iiib breast cancer