PHASE-II STUDY OF HIGH-DOSE CYCLOPHOSPHAMIDE, ETOPOSIDE, AND CARBOPLATIN (CEC) FOLLOWED BY AUTOLOGOUS HEMATOPOIETIC STEM-CELL RESCUE IN WOMEN WITH METASTATIC OR HIGH-RISK NONMETASTATIC BREAST-CANCER - MULTIVARIATE-ANALYSIS OF FACTORS AFFECTING SURVIVAL AND ENGRAFTMENT

Seventy women with high-risk stage II (n = 10), IIIA (n = 12), IIIB (n = 11), or IV (n = 37) breast cancer received cyclophosphamide 6000 mg /m(2), etoposide 2400 mg/m(2), and carboplatin 1200 mg/m(2) followed b y infusion of autologous hematopoietic stem cells (AHSC). Women with h igh-risk stage II disease had eight or more involved axillary lymph no des (n = 9) or axillary and breast relapse following lumpectomy, chemo therapy, and radiation therapy (n = 1). Women with measurable stage II I or stage IV disease were required to demonstrate complete or partial response to conventional-dose chemotherapy prior to transplant. The o verall (complete plus partial) response rate for the 31 patients not i n complete remission at the time of transplant was 55%. With a median follow-up of 545 days, the 2-year actuarial progression-free survival rates for patients with stage n, IIIA, IIIB and IV are 86, 75, 42 and 13%, respectively. Factors independently predictive of longer progress ion-free survival by multivariate analysis included lower stage diseas e, status of disease at transplant (in CR vs not in CR), and positive estrogen receptor status. Factors predictive of more rapid neutrophil engraftment by multivariate analysis included post-transplant administ ration of hematopoietic growth factors, greater number of infused CFU- GM, mobilization with G-CSF or cyclophosphamide/G-CSF (vs mobilization with GM-CSF or no mobilization), and lower stage disease. Only one pa tient (1.4%) died prior to day 100 from any cause. High-dose cyclophos phamide, etoposide, and carboplatin followed by infusion of AHSC const itutes an active and well-tolerated regimen in the treatment of women with high-risk non-metastatic or metastatic breast cancer.