Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies

Leukemia Research

Volumn 31, Issue 9, 2007, Pages 1165-1173

  Gojo, Ivana ^a   Tidwell, Michael L ^a   Greer, Jacqueline ^b   Takebe, Naoko ^a   Seiter, Karen ^c   Pochron, Mary F ^a   Johnson, Bonny ^d   Sznol, Mario ^d   Karp, Judith E ^b  

^a UNIVERSITY OF MARYLAND   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c NEW YORK MEDICAL COLLEGE   (United States)

^d Vion Pharmaceuticals Incorporated   (United States)

Author keywords

Acute myeloid leukemia; Chronic myeloid leukemia; Myeloproliferative disorders; Ribonucleotide reductase; Triapine

Indexed keywords

3 AMINOPICOLINALDEHYDE THIOSEMICARBAZONE; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE; ENZYME INHIBITOR; PYRIDINE DERIVATIVE; RIBONUCLEOTIDE REDUCTASE; THIOSEMICARBAZONE DERIVATIVE; UNCLASSIFIED DRUG;

ACIDOSIS; ADULT; AGED; ANOREXIA; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BONE PAIN; CANCER INHIBITION; CLINICAL ARTICLE; CLINICAL TRIAL; COLITIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEPRESSION; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; EDEMA; FACE EDEMA; FATIGUE; FEMALE; FEVER; HEADACHE; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERTENSION; HYPOALBUMINEMIA; HYPOTENSION; HYPOXIA; LETHARGY; LEUKEMIA; LEUKOCYTE COUNT; LIVER TOXICITY; MALE; METHEMOGLOBINEMIA; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MYALGIA; NAUSEA; NEUROPATHY; PAIN; PANCREATITIS; PANCYTOPENIA; PHASE 1 CLINICAL TRIAL; PRACTICE GUIDELINE; PRIORITY JOURNAL; PRURITUS; RASH; RIGOR; SIDE EFFECT; SWEATING; THORAX PAIN; TREATMENT RESPONSE; TUMOR LYSIS SYNDROME; UREMIA; VASODILATATION; VOMITING; WEIGHT REDUCTION; BLOOD; COHORT ANALYSIS; DRUG ANTAGONISM; INTRAVENOUS DRUG ADMINISTRATION; MAXIMUM TOLERATED DOSE; MIDDLE AGED;

ADULT; AGED; AGED, 80 AND OVER; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; LEUKEMIA; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PYRIDINES; RIBONUCLEOTIDE REDUCTASES; THIOSEMICARBAZONES;

EID: 34249888204     PISSN: 01452126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.leukres.2007.01.004     Document Type: Article

References (36)

1. Tallman M.S., Gilliland D.G., and Rowe J.M. Drug therapy for acute myeloid leukemia. Blood 106 4 (2005) 1154-1163
2. Reichard P., and Ehrenberg A. Ribonucleotide reductase-a radical enzyme. Science 221 4610 (1983) 514-519
3. Elford H.L., Freese M., Passamani E., and Morris H.P. Ribonucleotide reductase and cell proliferation: I. Variations of ribonucleotide reductase activity with tumor growth rate in a series of rat hepatomas. J Biol Chem 245 20 (1970) 5228-5233
4. Hurta R.A., Samuel S.K., Greenberg A.H., and Wright J.A. Early induction of ribonucleotide reductase gene expression by transforming growth factor beta 1 in malignant H-ras transformed cell lines. J Biol Chem 266 35 (1991) 24097-24100
5. Wright J.A., Chan A.K., Choy B.K., Hurta R.A., McClarty G.A., and Tagger A.Y. Regulation and drug resistance mechanisms of mammalian ribonucleotide reductase, and the significance to DNA synthesis. Biochem Cell Biol 68 12 (1990) 1364-1371
6. Zhou B.S., Tsai P., Ker R., et al. Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential. Clin Exp Metastasis 16 1 (1998) 43-49
7. Fan H., Huang A., Villegas C., and Wright J.A. The R1 component of mammalian ribonucleotide reductase has malignancy-suppressing activity as demonstrated by gene transfer experiments. Proc Natl Acad Sci USA 94 24 (1997) 13181-13186
8. Huang A., Fan H., Taylor W.R., and Wright J.A. Ribonucleotide reductase R2 gene expression and changes in drug sensitivity and genome stability. Cancer Res 57 21 (1997) 4876-4881
9. Hurta R.A., and Wright J.A. Mammalian drug resistant mutants with multiple gene amplifications: genes encoding the M1 component of ribonucleotide reductase, the M2 component of ribonucleotide reductase, ornithine decarboxylase, p5-8, the H-subunit of ferritin and the L-subunit of ferritin. Biochim Biophys Acta 1087 2 (1990) 165-172
10. Fan H., Villegas C., and Wright J.A. Ribonucleotide reductase R2 component is a novel malignancy determinant that cooperates with activated oncogenes to determine transformation and malignant potential. Proc Natl Acad Sci USA 93 24 (1996) 14036-14040
11. Tsimberidou A.M., Alvarado Y., and Giles F.J. Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies. Expert Rev Anticancer Ther 2 4 (2002) 437-448
12. Cory J.G., Sato A., and Brown N.C. Protein properties of the subunits of ribonucleotide reductase and the specificity of the allosteric site(s). Adv Enzyme Regul 25 (1986) 3-19
13. Reichard P. From RNA to DNA, why so many ribonucleotide reductases?. Science 260 5115 (1993) 1773-1777
14. Cory J.G., Cory A.H., Rappa G., et al. Inhibitors of ribonucleotide reductase. Comparative effects of amino- and hydroxy-substituted pyridine-2-carboxaldehyde thiosemicarbazones. Biochem Pharmacol 48 2 (1994) 335-344
15. Szekeres T., Fritzer-Szekeres M., and Elford H.L. The enzyme ribonucleotide reductase: target for antitumor and anti-HIV therapy. Crit Rev Clin Lab Sci 34 6 (1997) 503-528
16. Charache S., Terrin M.L., Moore R.D., et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 332 20 (1995) 1317-1322
17. Cortelazzo S., Finazzi G., Ruggeri M., et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332 17 (1995) 1132-1136
18. Hehlmann R., Heimpel H., Hasford J., et al. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group. Blood 82 2 (1993) 398-407
19. Sharon R., Tatarsky I., and Ben-Arieh Y. Treatment of polycythemia vera with hydroxyurea. Cancer 57 4 (1986) 718-720
20. Wattel E., Guerci A., Hecquet B., et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group. Blood 88 7 (1996) 2480-2487
21. Nyholm S., Thelander L., and Graslund A. Reduction and loss of the iron center in the reaction of the small subunit of mouse ribonucleotide reductase with hydroxyurea. Biochemistry 32 43 (1993) 11569-11574
22. Finch R.A., Liu M., 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 8 (2000) 983-991
23. Finch R.A., Liu M.C., Cory A.H., Cory J.G., and Sartorelli A.C. Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 3-AP): an inhibitor of ribonucleotide reductase with antineoplastic activity. Adv Enzyme Regul 39 (1999) 3-12
24. Liu M.C., Lin T.S., Penketh P., and Sartorelli A.C. Synthesis and antitumor activity of 4- and 5-substituted derivatives of isoquinoline-1-carboxaldehyde thiosemicarbazone. J Med Chem 38 21 (1995) 4234-4243
25. Chaston T.B., Lovejoy D.B., Watts R.N., and Richardson D.R. Examination of the antiproliferative activity of iron chelators: multiple cellular targets and the different mechanism of action of triapine compared with desferrioxamine and the potent pyridoxal isonicotinoyl hydrazone analogue 311. Clin Cancer Res 9 1 (2003) 402-414
26. Nyholm S., Mann G.J., Johansson A.G., Bergeron R.J., Graslund A., and Thelander L. Role of ribonucleotide reductase in inhibition of mammalian cell growth by potent iron chelators. J Biol Chem 268 35 (1993) 26200-26205
27. Thelander L., and Graslund A. Mechanism of inhibition of mammalian ribonucleotide reductase by the iron chelate of 1-formylisoquinoline thiosemicarbazone. Destruction of the tyrosine free radical of the enzyme in an oxygen-requiring reaction. J Biol Chem 258 7 (1983) 4063-4066
28. Cory J.G., Cory A.H., Rappa G., et al. Structure-function relationships for a new series of pyridine-2-carboxaldehyde thiosemicarbazones on ribonucleotide reductase activity and tumor cell growth in culture and in vivo. Adv Enzyme Regul 35 (1995) 55-68
29. Feun L., Modiano M., Lee K., et al. Phase I and pharmacokinetic study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) using a single intravenous dose schedule. Cancer Chemother Pharmacol 50 3 (2002) 223-229
30. 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 12 (2003) 1077-1083
31. Murren J., Modiano M., Clairmont C., et al. Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors. Clin Cancer Res 9 11 (2003) 4092-4100
32. Wadler S., Makower D., Clairmont C., Lambert P., Fehn K., and Sznol M. Phase I and pharmacokinetic study of the ribonucleotide reductase inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, administered by 96 h intravenous continuous infusion. J Clin Oncol 22 9 (2004) 1553-1563
33. Cheson B.D., Bennett J.M., Kantarjian H., et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96 12 (2000) 3671-3674
34. Cheson BD, Bennett JM, Kopecky KJ, 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 2003;21(24):4642-9.
35. Yen Y., Margolin K., Doroshow J., et al. A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer. Cancer Chemother Pharmacol 54 4 (2004) 331-342
36. Yee K.W., Cortes J., Ferrajoli A., et al. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leuk Res 30 7 (2006) 813-822