A phase I pharmacodynamic study of GTI-2040, an antisense oligonucleotide against ribonuclotide reductase, in acute leukemias: a California Cancer Consortium study

Mark H. Kirschbaum, Paul Frankel, Timothy W. Synold, Zhiliang Xie, Yun Yen, Leslie Popplewell, Robert Chen, Omar Aljitawi, Joseph M. Tuscano, Kenneth K. Chan, Edward M. Newman

研究成果: 雜誌貢獻文章

摘要

We performed a phase I study of GTI-2040, an antisense oligonucleotide against ribonucleotide reductase mRNA, on a novel dosing schedule of days 1–4 and 15–18 by continuous infusion to examine efficacy and tolerability in patients with leukemia. A dose of 11 mg/kg/d was safely reached. Dose-limiting toxicities (DLTs) at the higher levels included elevated troponin I and liver function enzymes. There were no objective responses to GTI-2040 in this study; 7/24 patients were able to complete the predetermined three infusion cycles. Pharmacokinetic and pharmacodynamic studies were performed, indicating a trend towards increasing intracellular drug levels and decreasing RRM2 gene expression with increasing doses. This dose schedule may be considered if appropriate combinations are identified in preclinical studies.

原文英語
頁(從 - 到)2307-2314
頁數8
期刊Leukemia and Lymphoma
57
發行號10
DOIs
出版狀態已發佈 - 十月 2 2016
對外發佈Yes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Kirschbaum, M. H., Frankel, P., Synold, T. W., Xie, Z., Yen, Y., Popplewell, L., Chen, R., Aljitawi, O., Tuscano, J. M., Chan, K. K., & Newman, E. M. (2016). A phase I pharmacodynamic study of GTI-2040, an antisense oligonucleotide against ribonuclotide reductase, in acute leukemias: a California Cancer Consortium study. Leukemia and Lymphoma, 57(10), 2307-2314. https://doi.org/10.3109/10428194.2016.1146947