A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders

Leukemia Research

Volumn 32, Issue 1, 2008, Pages 71-77

  Karp, Judith E ^a   Giles, Francis J ^b   Gojo, Ivana ^c   Morris, Lawrence ^d   Greer, Jacqueline ^a   Johnson, Bonny ^e   Thein, Mya ^a   Sznol, Mario ^e   Low, Jennifer ^f  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTER   (United States)

^d Blood and Marrow Transplant Group of Georgia   (United States)

^e Vion Pharmaceuticals Incorporated   (United States)

^f NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Fludarabine; Myeloproliferative disorders; Rbonucleotide reductase; Refractory acute leukemia; Triapine

Indexed keywords

3 AMINOPICOLINALDEHYDE THIOSEMICARBAZONE; ALLOPURINOL; CYTARABINE; ENZYME INHIBITOR; FLUDARABINE; HYDROXYUREA; IMATINIB; NUCLEOSIDE ANALOG; PARACETAMOL; RIBONUCLEOTIDE REDUCTASE; RIBONUCLEOTIDE REDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

ACUTE LEUKEMIA; ADULT; AGED; ARTICLE; BACTEREMIA; BONE MARROW SUPPRESSION; BONE PAIN; CANCER RESISTANCE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTINUOUS INFUSION; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; FEBRILE NEUTROPENIA; FEMALE; FEVER; GASTROINTESTINAL TOXICITY; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; HYPERPHOSPHATEMIA; KIDNEY DYSFUNCTION; LUNG MYCOSIS; MALE; METABOLIC ACIDOSIS; METHEMOGLOBINEMIA; MUCOSA INFLAMMATION; MYELOPROLIFERATIVE DISORDER; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; RECURRENT CANCER; SIDE EFFECT; SINUSITIS; TUMOR LYSIS SYNDROME; VIRAL GASTROENTERITIS;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; FEMALE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; MYELOPROLIFERATIVE DISORDERS; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PYRIDINES; RECURRENCE; THIOSEMICARBAZONES; TREATMENT OUTCOME; VIDARABINE;

EID: 36048952046     PISSN: 01452126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.leukres.2007.05.003     Document Type: Article

References (36)

1. Eklund H., Uhlin U., Farnegardh M., Logan D.T., and Nordlund P. Structure and function of the radical enzyme ribonucleotide reductase. Prog Biophys Mol Biol 77 (2001) 177-268
2. Wright J.A., Chan A.K., Choy B.K., Hurta R.A.R., McClarty G.A., and Tagger A.Y. Regulation and drug resistance mechanisms of mammalian ribonucleotide reductase, and the significant to DNA synthesis. Biochem Cell Biol 68 (1990) 1364-1371
3. Cory J.G., Cory A.H., Rappa G., Lorico A., Liu M.C., Lin T.S., et al. Inhibitors of ribonucleotide reductase. Comparative effects of amino- and hydroxy-substituted pyridine-2-carboxaldehyde thiosemicarbazones. Biochem Pharmacol 48 (1994) 335-344
4. Liu M.C., Lin T.S., Cory J.G., Cory A.H., and Sartorelli A.C. Synthesis and biologic activity of 3- and 5-amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone. J Med Chem 39 (1996) 2586-2593
5. Moore E.C., Booth B.A., and Sartorelli A.C. Inhibition of deoxyribonculeotide synthesis by pyridine carboxaldehyde thiosemicarbazones. Cancer Res 31 (1971) 235-238
6. Cortelazzo S., Finazzi G., Ruggeri M., Vestri O., Galli M., Rodeghiero F., et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332 (1995) 1132-1136
7. Hehlmann R., Heimpel H., Hasford J., et al. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. Blood 82 (1993) 398-407
8. Schwartz J.H., and Canellos G.P. Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia. Blood 46 (1975) 11-16
9. Spivak J.L. Polycythemia vera: myths, mechanisms, and management. Blood 100 (2002) 243-252
10. Wattel E., Guerci A., Hecquet B., et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Blood 88 (1996) 2480-2487
11. Finch R.A., Liu M.C., Grill S.P., et al. Triapine (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone): a potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem Pharmacol 59 (2000) 983-991
12. Nyholm S., Mann G.J., Johannson A.G., et al. Role of ribonucleotide reductase in inhibition of mammalian cell growth by potent iron chelators. J Biol Chem 268 (1993) 26200-26205
13. Giles F.J., Fracasso P.M., Kantarjian H.M., et al. Phase I and pharmacodynamic study of Triapine, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia. Leuk Res 27 (2003) 1077-1083
14. Gojo I., Tidwell M.L., Greer J., et al. Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, I adults with advanced hematologic malignancies. Leuk Res 31 (2007) 1173-1181
15. Bhalla K., Swerdlow P., and Grant S. Effects of thymidine and hydroxyurea on the metabolism and cytotoxicity of 1-B-D-arabinofuranosylcytosine in highly resistant human leukemic cells. Blood 78 (1991) 2937-2944
16. Colly L.P., Richel D.J., et al. Increase in Ara-C sensitivity in Ara-C sensitive and -resistant leukemia by stimulation of the salvage and inhibition of the de novo pathway. Ann Hematol 65 (1992) 26-32
17. Gandhi V., and Plunkett W. Modulation of arabinosylnucleoside metabolism by arabinosylnucleotides in human leukemic cells. Cancer Res 48 (1988) 329-334
18. Iwasaki H., Huang Peng, Keating M.J., and Plunkett W. Differential incorporation of Ara-C, gemcitabine, and fludarabine into replicating and repairing DNA in proliferating leukemia cells. Blood 90 (1997) 270-278
19. Rauscher III F., and Cadman E. Biochemical and cytokinetic modulation of L1210 and HL-60 cells by hydroxyurea and effect of 1-b-d-arabinofuranosylcytosine metabolism and cytotoxicity. Cancer Res 43 (1983) 2688-2693
20. Tanaka M., Kimura K., and Yoshida S. Mechanism of synergistic cell killing by hydroxyurea and cytosine arabinoside. Jpn J Cancer Res 76 (1985) 7290735
21. Walsh C.T., Craig R.W., and Agarwal R.P. Increased activation of 1-beta-D-arabinofuranosylcytosine by hydroxyurea in L1210 cells. Cancer Res 40 (1980) 3286-3292
22. Zhou B., Mi S., Mo X., Shih J., Tsai J., Hu E., et al. Time and sequence dependence of hydroxyurea in combination with gemcitabine in human KB cells. Anticancer Res 22 (2002) 1369-1377
23. Gandhi V., Plunkett W., Kantarjian H., Talpaz M., Robertson L.E., and O'Brien S. Cellular pharmacodynamics of parenterally infused hydroxyurea during a phase I clinical tiral in chronic myelogenous leukemia. J Clin Oncol 16 (1998) 2321-2331
24. Yee W.L.K., Garcia-Manero G., Verstovsek S., et al. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leuk Res 30 (2006) 813-822
25. Chun H.G., Leyland-Jones B., and Cheson B.D. Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. J Clin Oncol 9 (1991) 175-188
26. Huang P., and Plunkett W. Fludarabine- and gemcitabine-induced apoptosis: incorporation of analogs into DNA is a critical event. Cancer Chemother Pharmacol 3 (1995) 181-188
27. Gandhi V., Estey E., Keating M.J., and Plunkett W. Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol 11 (1993) 116-124
28. Chun H.G., Leyland-Jones B.R., Caryk S.M., and Hoth D. Central nervous system toxicity of fludarabine phosphate. Cancer Treat Rep 70 (1986) 1225-1228
29. Warrell Jr. R.P., and Berman E. Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity. J Clin Oncol 4 (1986) 74-79
30. Kano Y., Akutsu M., Tsunoda S., Suzuki K., Ichikawa A., Furukawa Y., et al. In vitro cytotoxic effects of fludarabine (2-F-ara-A) in combination with commonly used antileukemic agents by isobologram analysis. Leukemia 14 (2000) 3379-3388
31. Estey E., Thall P., Andreeff M., et al. Use of granulocyte colony-stimulating factor before, during and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony stimulating factor. J Clin Oncol 12 (1994) 671-678
32. Dinndorf P.A., Avramis V.I., Wiersma S., et al. Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Clindren's Cancer Group. J Clin Oncol 15 (1997) 2780-2785
33. Fleischhack G., Hasan C., Graf N., Mann G., and Bode U. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Britisih J Haem 102 (1998) 647-655
34. Cheson B.D., Bennett J.M., Kopecky K.J., et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 21 (2003) 4642-4649
35. Cheson B.D., Bennett J.M., Kantarjian H.M., et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96 (2000) 3671-3674
36. Giles F.J., Karp J.E., Silverman L., et al. Phase II study of SU5416, a small molecule vascular endothelial growth factor (VEGF) tyrosine kinase receptor inhibitor, in patients with refractory myeloproliferative diseases. Cancer 97 (2003) 1920-1928