Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer

City of Hope Medical Center72 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer

Interventions

filgrastimBIOLOGICAL

Given IV or subcutaneously

carboplatinDRUG

Given IV

cyclophosphamideDRUG

Given IV

doxorubicin hydrochloride

Eligibility

Sex: ALLMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (2)

Banner Good Samaritan Medical Center

Phoenix, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Outcomes

Primary Outcomes

Five-Year Relapse-free Survival

RFS events included death or disease recurrence. Patients who did not experience disease recurrence or death were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method.

Time frame: Five years

Secondary Outcomes

Five-Year Overall Survival

Patients who were still alive were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method.

Time frame: Five Years

Data from ClinicalTrials.gov

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