High-Dose Chemotherapy and Autologous Blood Cell Transplantation in Treating Patients With Primary, Locally Advanced, or Stage IV Breast Cancer

OBJECTIVES: I. Determine the maximum tolerated doses of mitoxantrone and cyclophosphamide when administered in combination with thiotepa, autologous blood cells, and amifostine in patients with primary, locally advanced, or metastatic breast cancer, and determine whether amifostine, a cytoprotection agent, allows administration of high dose chemotherapy. II. Determine the dose limiting toxicities of this regimen when administered to patients with primary, locally advanced, or metastatic breast cancer. III. Evaluate the toxicities of amifostine, a cytoprotection agent, when administered in multiple doses to breast cancer patients receiving high dose chemotherapy and autologous blood cell transplantation. IV. Document the antitumor efficacy of this regimen versus freedom from recurrence and overall survival after autologous blood cell transplantation. V. Assess the contribution of disease, treatment, and personal characteristics affecting the quality of life in these patients and the patient's primary caregiver.

OUTLINE: This is a dose escalation study. Autologous blood cells are collected after completion of neoadjuvant/induction chemotherapy (and salvage mastectomy, if indicated). Patients receive IV amifostine, mitoxantrone, and thiotepa on day -7. On day -6, patients receive IV amifostine, thiotepa, and cyclophosphamide treatment. On days -5, -4, and -3, IV amifostine and cyclophosphamide are administered to participants. Following high dose chemotherapy treatment, patients rest on days -2 and -1. On day 0, patients undergo autologous blood cell transplantation. Cohorts of 3 patients each receive escalating doses of mitoxantrone and cyclophosphamide. If 1 of 3 patients at a given dose level experiences dose limiting toxicity (DLT), an additional 3 patients are treated at that dose. If at least 3 of 6 patients experience DLT at a given dose level, then the maximum tolerated dose is the previous dose level. Patients are followed at day 100, then every 6 months for 2 years, then annually until death.

PROJECTED ACCRUAL: A total of 30 patients will be accrued.