TY - JOUR
T1 - Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome
AU - Yee, Karen W L
AU - Cortes, Jorge
AU - Ferrajoli, Alessandra
AU - Garcia-Manero, Guillermo
AU - Verstovsek, Srdan
AU - Wierda, William
AU - Thomas, Deborah
AU - Faderl, Stefan
AU - King, Ivan
AU - O'Brien, Susan M.
AU - Jeha, Sima
AU - Andreeff, Michael
AU - Cahill, Ann
AU - Sznol, Mario
AU - Giles, Francis J.
N1 - Funding Information:
Supported in part by a Canadian Cancer Society-Ontario Division Fellowship.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/7
Y1 - 2006/7
N2 - Triapine®, an iron chelator and a potent inhibitor of ribonucleotide reductase, has significant anti-leukemia activity. A phase I study of Triapine in combination with ara-C was conducted in 32 patients with refractory acute leukemia and high-risk MDS. Triapine (105 mg/m2/day 6-h infusion) was followed immediately by ara-C [100 (n = 4), 200 (n = 6), 400 (n = 7), or 800 (n = 8) mg/m2/day] as an 18-h infusion for 5 consecutive days. Dose-limiting toxicities (DLTs) were observed at the 800 mg/m2 ara-C dose level (one patient each with grade 4 mucositis; grade 4 neutropenic colitis, sepsis; grade 4 neuropathy; and grade 4 hyperbilirubinemia). Therefore, the study was amended to include an ara-C dose level of 600 mg/m2/day, no DLTs occurred in seven patients treated at this dose level. Mean Triapine Cmax and AUC were 1.13 μg/mL and 251.5 min μg/mL. Of 31 evaluable patients, 4 (13%) (3 AML, 1 Ph + ALL) achieved a CR (1 at a dose of 800 mg/m2; 2 at 600 mg/m2; 1 at 200 mg/m2). The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks.
AB - Triapine®, an iron chelator and a potent inhibitor of ribonucleotide reductase, has significant anti-leukemia activity. A phase I study of Triapine in combination with ara-C was conducted in 32 patients with refractory acute leukemia and high-risk MDS. Triapine (105 mg/m2/day 6-h infusion) was followed immediately by ara-C [100 (n = 4), 200 (n = 6), 400 (n = 7), or 800 (n = 8) mg/m2/day] as an 18-h infusion for 5 consecutive days. Dose-limiting toxicities (DLTs) were observed at the 800 mg/m2 ara-C dose level (one patient each with grade 4 mucositis; grade 4 neutropenic colitis, sepsis; grade 4 neuropathy; and grade 4 hyperbilirubinemia). Therefore, the study was amended to include an ara-C dose level of 600 mg/m2/day, no DLTs occurred in seven patients treated at this dose level. Mean Triapine Cmax and AUC were 1.13 μg/mL and 251.5 min μg/mL. Of 31 evaluable patients, 4 (13%) (3 AML, 1 Ph + ALL) achieved a CR (1 at a dose of 800 mg/m2; 2 at 600 mg/m2; 1 at 200 mg/m2). The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks.
KW - Acute lymphocytic leukemia
KW - Acute myeloid leukemia
KW - Cytarabine
KW - Myelodysplastic syndrome
KW - Ribonucleotide reductase
KW - Triapine
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UR - http://www.scopus.com/inward/citedby.url?scp=33744526999&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2005.12.013
DO - 10.1016/j.leukres.2005.12.013
M3 - Article
C2 - 16478631
AN - SCOPUS:33744526999
SN - 0145-2126
VL - 30
SP - 813
EP - 822
JO - Leukemia Research
JF - Leukemia Research
IS - 7
ER -
