A RANDOMIZED TRIAL OF 2 DOSES OF CYCLOPHOSPHAMIDE WITH ETOPOSIDE AND G-CSF FOR MOBILIZATION OF PERIPHERAL-BLOOD STEM-CELLS IN 318 PATIENTS WITH STAGE-II-STAGE-III BREAST-CANCER

The purpose of this study was to develop a less toxic outpatient chemo therapy regimen for mobilizing peripheral blood stem cells (PBSC). Thr ee hundred eighteen patients with newly diagnosed stage II-III breast cancer who had received conventional dose adjuvant chemotherapy were r andomized to receive intermediate-dose cyclophosphamide (2 g/m(2)), et oposide (600 mg/m(2)), and granulocyte colony-stimulating factor (G-CS F) 6 mu g/kg/day (ID-Cy, n = 162) or high-dose cyclophosphamide (4 g/m (2)) and the same doses of etoposide and G-CSF (HD-Cy, n = 156) follow ed by collection of PBSC. Three hundred seventeen of 318 patients had apheresis performed, and 315 received high-dose chemotherapy (HDC) fol lowed by PBSC support. The median numbers of CD34+ cells collected in a median of two aphereses following ID-Cy and HD-Cy were 19.9 and 22.2 x 10(6)/kg, respectively (p = 0.04). The fractions of patients achiev ing CD34+ cell doses greater than or equal to 2.5 or greater than or e qual to 5.0 x 10(6)/kg were not different between the two regimens. Mo re patients receiving HD-Cy had grade 3-4 nausea (p = 0.001), vomiting (p = 0.03), and mucositis (p = 0.04). The fractions of patients havin g a neutrophil nadir <0.5 x 10(9)/L following ID-CST and HD-Cy were 0. 83 and 0.95, respectively (p <0.001). The fractions of patients having a platelet nadir <25 x 10(9)/L following ID-Cy and HD-Cy were 0.13 an d 0.51, respectively (p= <0.001). More patients in the HD-Cy group rec eived platelet (p < 0.001) and red blood cell (p < 0.001) transfusions and were admitted to the hospital more frequently (p = 0.03) than pat ients receiving ID-Cy. Three hundred fifteen patients received HDC fol lowed by infusion of PBSC. There were no significant differences in th e incidence of transplant-related death or early survival between pati ents receiving ID-Cy or HD-Cy followed by HDC. It was concluded that a regimen of Cy 2 g/m(2) with etoposide and G-CSF was effective for mob ilization of PBSC with low morbidity and resource utilization in patie nts with limited prior chemotherapy exposure.