A Randomized Trial of Two Doses of Cyclophosphamide with Etoposide and G-CSF for Mobilization of Peripheral Blood Stem Cells in 318 Patients with Stage II-III Breast Cancer

Abstract

The purpose of this study was to develop a less toxic outpatient chemotherapy regimen for mobilizing peripheral blood stem cells (PBSC). Three hundred eighteen patients with newly diagnosed stage II-III breast cancer who had received conventional dose adjuvant chemotherapy were randomized to receive intermediate-dose cyclophosphamide (2 g/m²), etoposide (600 mg/m²), and granulocyte colony-stimulating factor (G-CSF) 6 μg/kg/day (ID-Cy, n = 162) or high-dose cyclophosphamide (4 g/m²) and the same doses of etoposide and G-CSF (HD-Cy, n = 156) followed by collection of PBSC. Three hundred seventeen of 318 patients had apheresis performed, and 315 received high-dose chemotherapy (HDC) followed 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 10⁶/kg, respectively (p = 0.04). The fractions of patients achieving CD34+ cell doses ≥2.5 or ≥5.0 X 106/kg were not different between the two regimens. More 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 having a neutrophil nadir <0.5 X 10⁹/L following ID-Cy and HD-Cy were 0.83 and 0.95, respectively (p = <0.001). The fractions of patients having a platelet nadir <25 X 10⁹/L following ID-Cy and HD-Cy were 0.13 and 0.51, respectively (p = <0.001). More patients in the HD-Cy group received platelet (p < 0.001) and red blood cell (p < 0.001) transfusions and were admitted to the hospital more frequently (p = 0.03) than patients receiving ID-Cy. Three hundred fifteen patients received HDC followed by infusion of PBSC. There were no significant differences in the incidence of transplant-related death or early survival between patients receiving ID-Cy or HD-Cy followed by HDC. It was concluded that a regimen of Cy 2 g/m² with etoposide and G-CSF was effective for mobilization of PBSC with low morbidity and resource utilization in patients with limited prior chemotherapy exposure.