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

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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)813-822
Number of pages10
JournalLeukemia Research
Volume30
Issue number7
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Cytarabine
Leukemia
Ribonucleotide Reductases
Mucositis
Hyperbilirubinemia
Colitis
Chelating Agents
Area Under Curve
Sepsis
Iron
3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Keywords

  • Acute lymphocytic leukemia
  • Acute myeloid leukemia
  • Cytarabine
  • Myelodysplastic syndrome
  • Ribonucleotide reductase
  • Triapine

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Yee, K. W. L., Cortes, J., Ferrajoli, A., Garcia-Manero, G., Verstovsek, S., Wierda, W., ... Giles, F. J. (2006). Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leukemia Research, 30(7), 813-822. https://doi.org/10.1016/j.leukres.2005.12.013

Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. / Yee, Karen W.L.; Cortes, Jorge; Ferrajoli, Alessandra; Garcia-Manero, Guillermo; Verstovsek, Srdan; Wierda, William; Thomas, Deborah; Faderl, Stefan; King, Ivan; O'Brien, Susan M.; Jeha, Sima; Andreeff, Michael; Cahill, Ann; Sznol, Mario; Giles, Francis J.

In: Leukemia Research, Vol. 30, No. 7, 01.07.2006, p. 813-822.

Research output: Contribution to journalArticle

Yee, KWL, Cortes, J, Ferrajoli, A, Garcia-Manero, G, Verstovsek, S, Wierda, W, Thomas, D, Faderl, S, King, I, O'Brien, SM, Jeha, S, Andreeff, M, Cahill, A, Sznol, M & Giles, FJ 2006, 'Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome', Leukemia Research, vol. 30, no. 7, pp. 813-822. https://doi.org/10.1016/j.leukres.2005.12.013
Yee, Karen W.L. ; Cortes, Jorge ; Ferrajoli, Alessandra ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Wierda, William ; Thomas, Deborah ; Faderl, Stefan ; King, Ivan ; O'Brien, Susan M. ; Jeha, Sima ; Andreeff, Michael ; Cahill, Ann ; Sznol, Mario ; Giles, Francis J. / Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. In: Leukemia Research. 2006 ; Vol. 30, No. 7. pp. 813-822.
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abstract = "Triapine{\circledR}, 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.",
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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.

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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.

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