Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study.
To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II-IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration-time curve of the first administration remained at less than 1500 micromol min/l in 27 of the 29 patients (93%), and between 900 and 1350 micromol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.
Kim
S-W
SW
Hematology and Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
Mori
S-i
SI
Tanosaki
R
R
Fukuda
T
T
Kami
M
M
Sakamaki
H
H
Yamashita
T
T
Kodera
Y
Y
Terakura
S
S
Taniguchi
S
S
Miyakoshi
S
S
Usui
N
N
Yano
S
S
Kawano
Y
Y
Nagatoshi
Y
Y
Harada
M
M
Morishima
Y
Y
Okamoto
S
S
Saito
A M
AM
Ohashi
Y
Y
Ueda
R
R
Takaue
Y
Y
D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease; D006098:Granulocytes / Q000166:cytology; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
D003520:Cyclophosphamide; D002066:Busulfan