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 μg/kg dose groups were 5.4, 34.3, 55.0 and 127.6 cells/μl, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 μg/kg dose groups were 0.01, 0.33, 1.32 and 3.30 CFU-GMs/μl, 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 × 10⁶ CD34⁺ 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.