A phase I and pharmacokinetic study of XK469R (NSC 698215), a quinoxaline phenoxypropionic acid derivative, in patients with refractory acute leukemia.

Investigational New Drugs
Wendy StockFrancis Giles

Abstract

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.

References

Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·H GaoR M Snapka
Mar 27, 2002·Cancer Chemotherapy and Pharmacology·Hong LinBen D Chen
Apr 4, 2002·Journal of Pharmaceutical and Biomedical Analysis·Hui ZhengKenneth K Chan
Feb 4, 2006·Reproductive Biomedicine Online·V BaltaciA Aktan
Sep 2, 2006·Cancer·Alfonso Quintas-CardamaSrdan Verstovsek

❮ Previous
Next ❯

Citations

Apr 2, 2009·Expert Opinion on Investigational Drugs·Camilla StapnesØystein Bruserud
Sep 23, 2010·Pediatric Blood & Cancer·Nisha C KakodkarSusan L Cohn
Sep 7, 2016·European Journal of Medicinal Chemistry·Qiao-Hong XiaXun Li
Jun 1, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Christine Beedham

❮ Previous
Next ❯

Related Concepts

Related Papers

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Samir D UndeviaM J Ratain
© 2022 Meta ULC. All rights reserved