1. Phase I study of GTI-2040, a ribonucleotide reductase antisense, with high dose cytarabine in patients with relapsed/refractory acute myeloid leukemia
- Author
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Steven M. Devine, Zhiliang Xie, Zhongfa Liu, William Blum, Cheryl Kefauver, Michael R. Grever, Kenneth K. Chan, Lenguyen Huynh, Rebecca B. Klisovic, James A. Zwiebel, Guido Marcucci, and John C. Byrd
- Subjects
Male ,Antimetabolites, Antineoplastic ,Cancer Research ,government.form_of_government ,Pharmacology ,Biology ,Article ,High dose cytarabine ,Refractory ,medicine ,Humans ,Cytotoxicity ,Aged ,Antisense therapy ,Cytarabine ,Myeloid leukemia ,Hematology ,Middle Aged ,Phase i study ,Leukemia, Myeloid, Acute ,Ribonucleotide reductase ,Oligodeoxyribonucleotides ,Oncology ,government ,Cancer research ,Female ,Neoplasm Recurrence, Local ,medicine.drug - Abstract
We hypothesized that GTI-2040, a 20-mer oligonucleotide complementary to the R2 subunit mRNA of ribonucleotide reductase, combined with high dose cytarabine (HiDAC) would result in enhanced cytotoxicity by favoring Ara-CTP DNA incorporation. In a phase I dose escalation trial, adults (≥ 60 years) with refractory or relapsed acute myeloid leukemia (AML) received daily HiDAC plus infusional GTI-2040. Using a novel assay, evidence of intracellular drug accumulation and target R2 down-regulation was observed. GTI-2040/HiDAC can be administered safely. However, with no complete remissions observed, alternative doses and schedules may need to be investigated to achieve clinical activity in older patients with AML.
- Published
- 2013
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