Abstract
Triapine®, a potent inhibitor of ribonucleotide reductase, has demonstrated anti-leukemia activity in pre-clinical models. We conducted a Phase I study of Triapine administered as a 2 h infusion for 5 days in 25 adults with advanced leukemias. We established that Triapine at 96 mg/m2 once a day can be given safely on days 1-5 and 15-19 or 1-5 and 8-12 of a 4-week cycle. When administered twice a day on days 1-5 and 8-12, the maximum tolerated dose of Triapine appears to be 64 mg/m2, although the true criteria for DLT were not met by protocol definition. No CR or PR were observed, but 76% of patients had a >50% reduction in white blood cell counts. At all dose levels, the peak plasma concentration of Triapine (2.2-5.5 μM) was above levels required to achieve in vitro/in vivo leukemia growth inhibition. Based on these data, we conclude that Triapine warrants further investigation in hematologic malignancies.
Original language | English (US) |
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Pages (from-to) | 1165-1173 |
Number of pages | 9 |
Journal | Leukemia Research |
Volume | 31 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- Acute myeloid leukemia
- Chronic myeloid leukemia
- Myeloproliferative disorders
- Ribonucleotide reductase
- Triapine
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research