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.

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 micrograms/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 apheresis following ID-Cy and HD-Cy were 19.9 and 22.2 x 10(6)/kg, respectively (p = 0.04). The fractions of patients achieving CD34+ cell doses > or = 2.5 or > or = 5.0 x 10(6)/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 10(9)/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 10(9)/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.

Collection of peripheral blood stem cells following administration of paclitaxel, cyclophosphamide, and filgrastim in patients with breast and ovarian cancer.

PURPOSE: To determine the toxicities and efficacy of paclitaxel, cyclophosphamide (Cy), and recombinant human granulocyte-colony stimulating factor (filgrastim) administered for mobilization and collection of peripheral blood stem cells (PBSC) in patients with breast and ovarian cancer. METHODS: One hundred and forty-one patients with breast (n = 115) or ovarian cancer (n = 26) received paclitaxel 170 mg/m2 and Cy 2 gm/m2 (n = 42) or paclitaxel 200 mg/m2, Cy 3 gm/m2 (n = 99), and filgrastim (6 micrograms/kg/day) followed by collection of PBSC by apheresis. RESULTS: The 2 dose levels of paclitaxel and Cy tested were well tolerated. The median yield of CD34+ cells from all patients was 6.53 x 10(6)/kg (range, 0.11-51.76) collected with a median of 2 aphereses (range, 1-8). The target dose of 2.5 x 10(6) CD34+ cells/kg was achieved in 85% of patients. The mean daily collection of CD34+ cells was 5.46 x 10(6)/kg for patients receiving 200 mg/m2 of paclitaxel and 3 gm/m2 of Cy as compared to 2.77 for patients receiving the lower doses (p = 0.0005). Increasing the dose of paclitaxel and Cy did not significantly increase the fraction of patients achieving a target dose of 2.5 x 10(6) CD34+ cells/kg (87% vs 81%, p = 0.367) but did increase the fraction achieving a target of 5.0 x 10(6) CD34+ cells/kg (73% vs 45%, p = 0.002). The mean daily collection of CD34+ cells for patients who had received only 1 prior chemotherapy regimen was 6.59 x 10(6)/kg as compared to 3.47 for patients who had received more than 1 prior chemotherapy regimen (p < 0.0001). Prior radiation therapy (p = 0.003) and patient performance status (p = 0.047) were adverse risk factors for achieving a target dose of > or = 2.5 x 10(6) CD34+ cells/kg. CONCLUSIONS: The combination of paclitaxel, Cy, and filgrastim can be administered with acceptable toxicity, allowing collection of adequate quantities of PBSC from the majority of patients with breast and ovarian cancer. Increasing the doses of paclitaxel and Cy increased the number of CD34+ cells collected and decreased the number of apheresis procedures necessary to collect target cell doses. However, increasing drug doses did not increase the fraction of patients yielding the minimum CD34+ target dose of 2.5 x 10(6)/kg. Collection of PBSC early in the disease course is the best strategy to assure optimal CD34+ cell doses in all patients.