TY - JOUR
T1 - A phase I and pharmacokinetic study of XK469R (NSC 698215), a quinoxaline phenoxypropionic acid derivative, in patients with refractory acute leukemia
AU - Stock, Wendy
AU - Undevia, Samir D.
AU - Bivins, Carol
AU - Ravandi, Farhad
AU - Odenike, Olatoyosi
AU - Faderl, Stefan
AU - Rich, Elizabeth
AU - Borthakur, Gautam
AU - Godley, Lucy
AU - Verstovsek, Srdan
AU - Artz, Andrew
AU - Wierda, William
AU - Larson, Richard A.
AU - Zhang, Yanming
AU - Cortes, Jorge
AU - Ratain, Mark J.
AU - Giles, Francis J.
N1 - Funding Information:
This work was supported by CA069852 and CA062461 and by the University of Chicago Cancer Research Center, P30 CA014599-32 S2. W.Stock(*).S.D.Undevia.O.Odenike.E.Rich. L. Godley.A. Artz.R. A. Larson.Y. Zhang.M. J. Ratain Section of Hematology/Oncology, University of Chicago Cancer Research Center, 5841 S. Maryland, M/C 2115, Chicago, IL 60637, USA e-mail: [email protected]
PY - 2008/8
Y1 - 2008/8
N2 - A phase I study was performed to determine the safety and pharmacokinetics of XK469R in patients with refractory acute leukemia. The study aimed to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of XK469R given intravenously over 30 to 60 min on days 1, 3, and 5 of a 21 day cycle. Patients were treated in successive cohorts of six until DLT was observed. Once the MTD was determined, an additional cohort of six patients was enrolled at the previous dose level and that dose was considered the recommended phase 2 dose (RPTD). Forty-six patients were treated at dose levels of 1,400, 1,750, 2,200, and 2,750 mg. The DLTs were: mucositis, colitis and hyperbilirubinemia. Reversible myelosuppression was noted at all dose levels. One (2%) of 42 patients achieved a complete remission and five patients (11%) had hematologic improvement. The half-life of the drug was long with a mean value of 48 h. The mean clearance was 206 mL/h with a coefficient of variation of 32%. No correlation was observed between the development of DLT and pharmacokinetics. The RTPD is 1,750 mg. XK469R induced hematological responses in patients with refractory leukemia at tolerable doses.
AB - A phase I study was performed to determine the safety and pharmacokinetics of XK469R in patients with refractory acute leukemia. The study aimed to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of XK469R given intravenously over 30 to 60 min on days 1, 3, and 5 of a 21 day cycle. Patients were treated in successive cohorts of six until DLT was observed. Once the MTD was determined, an additional cohort of six patients was enrolled at the previous dose level and that dose was considered the recommended phase 2 dose (RPTD). Forty-six patients were treated at dose levels of 1,400, 1,750, 2,200, and 2,750 mg. The DLTs were: mucositis, colitis and hyperbilirubinemia. Reversible myelosuppression was noted at all dose levels. One (2%) of 42 patients achieved a complete remission and five patients (11%) had hematologic improvement. The half-life of the drug was long with a mean value of 48 h. The mean clearance was 206 mL/h with a coefficient of variation of 32%. No correlation was observed between the development of DLT and pharmacokinetics. The RTPD is 1,750 mg. XK469R induced hematological responses in patients with refractory leukemia at tolerable doses.
KW - Myelosuppression
KW - Phase I study
KW - Refractory leukemia
KW - XK469R
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U2 - 10.1007/s10637-008-9129-0
DO - 10.1007/s10637-008-9129-0
M3 - Article
C2 - 18425419
AN - SCOPUS:45849127601
SN - 0167-6997
VL - 26
SP - 331
EP - 338
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 4
ER -