A Dose-finding Study of Lenograstim (Glycosylated rHuG-CSF) for Peripheral Blood Stem Cell Mobilization during Postoperative Adjuvant Chemotherapy in Patients with Breast Cancer

Background:The optimum dose of granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell (PBSC) mobilization after disease-oriented, conventional-dose chemotherapy remains unknown.Methods:A multicenter dose-finding study of glycosylated G-CSF (lenograstim) for the mobilization of PBSCs following adjuvant CAF chemotherapy (cyclophosphamide, doxorubicin and 5-fluorouracil) was performed in 38 patients with postoperative breast cancer. Each 10, ten and eight patients were sequentially allocated to one of the three dose groups (2,5 and 10 µg/kg, respectively) of lenograstim. Lenograstim was administered subcutaneously (s.c.) daily from day 8 to the day of the last apheresis and CD34+ cells and colony-forming units—granulocyte macrophage (CFU-GMs) in peripheral blood were measured serially. Additionally, 10 patients who received adjuvant CAF chemotherapy alone also participated in the study, as a control.Results:Lenograstim was well tolerated up to 10 µg/kg, except for one patient given 10 µg/kg who developed transient grade 3 hepatic enzyme elevation. The peak levels of CD34+ cells and CFU-GMs in peripheral blood showed dose—response relationships. The median peak CD34+ cells for the 0,2,5 and 10 Ég/kg dose groups were 5.4,34.3, 55.0 and 127.6 cells/Él, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 Ég/kg dose groups were 0.01, 0.33,1.32 and 3.30 CFU-GMs/Él, respectively.Conclusions:Considering the previous reports suggesting that a pre-apheresis number of 40–50 CD34+ cells/µl in peripheral blood is highly predictive for achievement of more than 2.5 × 106CD34+ cells/kg in a standard apheresis procedure of 10 litres, the optimum dose of lenograstim for PBSC mobilization following CAF chemotherapy in patients with postoperative breast cancer is 5 µg/kg/day s.c.