Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome.

Abstract

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 C(max) and AUC were 1.13 microg/mL and 251.5 minmicrog/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 200mg/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.

• Authors: Karen W L Yee, Jorge Cortes, Alessandra Ferrajoli, Guillermo Garcia-Manero, Srdan Verstovsek, William Wierda, Deborah Thomas, Stefan Faderl, Ivan King, Susan M O'brien, Sima Jeha, Michael Andreeff, Ann Cahill, Mario Sznol, Francis J Giles
• Journal: Leukemia research (Leuk Res) Vol. 30 Issue 7 Pg. 813-22 (Jul 2006) ISSN: 0145-2126 [Print] England
• PMID: 16478631 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Drug Combinations
• Pyridines
• Thiosemicarbazones
• Cytarabine
• 3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacokinetics)
• Cytarabine (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Combinations
• Female
• Humans
• Injections, Intravenous
• Leukemia, Myeloid (diagnosis, drug therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Myelodysplastic Syndromes (diagnosis, drug therapy)
• Pyridines (administration & dosage, adverse effects, pharmacokinetics)
• Recurrence
• Risk Factors
• Thiosemicarbazones (administration & dosage, adverse effects, pharmacokinetics)
• Treatment Outcome