A dose-finding study of lenograstim (glycosylated rHuG-CSF) for peripheral blood stem cell mobilization during postoperative adjuvant chemotherapy in patients with breast cancer. Lenograstim/Breast Cancer Study Group.
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 micrograms/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 micrograms/kg, except for one patient given 10 micrograms/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 micrograms/kg dose groups were 5.4, 34.3, 55.0 and 127.6 cells/microliter, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 micrograms/kg dose groups were 0.01, 0.33, 1.32 and 3.30 CFU-GMs/microliter, respectively.


CONCLUSIONS
Considering the previous reports suggesting that a pre-apheresis number of 40-50 CD34+ cells/microliter in peripheral blood is highly predictive for achievement of more than 2.5 x 10(6) 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 micrograms/kg/day s.c.
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
M
M
Narabayashi
K
K
Takeyama
T
T
Fukutomi
Y
Y
Tokuda
T
T
Tajima
A
A
Okumura
T
T
Chou
M
M
Sano
H
H
Makino
T
T
Igarashi
Y
Y
Sasaki
S
S
Imoto
M
M
Ogura
Y
Y
Morishima
H
H
Murai
S
S
Okamoto
T
T
Ikeda
M
M
Kasai
T
T
Yokozawa
K
K
Tobinai
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D018952:Antigens, CD34 / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001781:Blood Component Removal; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006098:Granulocytes / Q000166:cytology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007279:Injections, Subcutaneous; D000078224:Lenograstim; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008408:Mastectomy; D008875:Middle Aged; D011182:Postoperative Care; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D018952:Antigens, CD34; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil