期刊
LEUKEMIA RESEARCH
卷 32, 期 1, 页码 71-77出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2007.05.003
关键词
refractory acute leukemia; myeloproliferative disorders; rbonucleotide reductase; Triapine; fludarabine
资金
- NCI NIH HHS [U01 CA70095, U01 CA070095, U01 CA070095-14] Funding Source: Medline
- NCRR NIH HHS [M01-RR0052, M01 RR000052] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [U01CA070095] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000052] Funding Source: NIH RePORTER
Triapine((R)) is a potent ribonucleotide reductase (RR) inhibitor that depletes intracellular deoxyribonculeotide pools, especially dATP. We designed a Phase I trial of Triapine followed by the adenosine analog fludarabine in adults with refractory acute leukemias and aggressive myeloproliferative disorders (MPD). Two schedules were examined: (A) Triapine 105 mg/m(2)/day over 24 h followed by fludarabine daily x 5 (24 patients, fludarabine 15-30 mg/m(2)/dose); (B) Triapine 200mg/m(2) over 24 h followed by 5 days of fludarabine 30 mg/m(2) /day (9 patients). Complete and partial responses (CR, PR) Occurred in Schedule A (5/24, 21 %), with CR occurring at the 2 highest fludarabine doses (2/12, 17%). In contrast, no CR or PR Occurred in Schedule B. Four of the 5 responses occurred in patients with underlying MPD (4/14, 29%). Drug-related toxicities included fever and metabolic acidosis. Triapine 105 mg/m(2) followed by fludarabine 30 mg/m2 daily x 5 is active in refractory myeloid malignancies and warrants continuing study for patients with aggressive MPD. (c) 2007 Elsevier Ltd. All rights reserved.
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