Phase II pilot study of oral dasatinib in patients with higher-risk myelodysplastic syndrome (MDS) who failed conventional therapy

Leukemia Research

Volumn 37, Issue 3, 2013, Pages 300-304

  Duong, Vu H ^a   Jaglal, Michael V ^b   Zhang, Ling ^b   Kale, Vishakha ^c   Lancet, Jeffrey E ^b   Komrokji, Rami S ^b   List, Alan F ^b  

^a UNIVERSITY OF MARYLAND   (United States)

^b H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^c SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

Author keywords

Azacitidine; Dasatinib; Decitabine; Myelodysplastic syndromes; Myelodysplastic myeloproliferative diseases

Indexed keywords

DASATINIB; NUCLEOSIDE ANALOG; PROTEIN KINASE LYN; PROTEIN TYROSINE KINASE;

ABDOMINAL PAIN; ACNE; ACUTE GRANULOCYTIC LEUKEMIA; ADULT; AGED; ANOREXIA; ARTICLE; CANCER RISK; CELL PROLIFERATION; CHRONIC MYELOMONOCYTIC LEUKEMIA; CLINICAL ARTICLE; CONSTIPATION; CONTINUOUS INFUSION; CONTROLLED STUDY; COUGHING; DIAPHORESIS; DIARRHEA; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ERUPTION; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG SAFETY; DYSGEUSIA; DYSPNEA; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; GASTROINTESTINAL HEMORRHAGE; HEMOGLOBINOPATHY; HIGH RISK PATIENT; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LEUKOCYTE DISORDER; MALE; MONOCYTE MACROPHAGE PRECURSOR CELL; MYELOBLAST; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; NEUTROPHIL COUNT; ORAL MUCOSITIS; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; PILOT STUDY; PLEURA EFFUSION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REFRACTORY ANEMIA WITH EXCESS BLASTS; SIDE EFFECT; SKIN BRUISING; THORAX PAIN; THROMBOCYTE ANOMALY; TREATMENT RESPONSE; VISUAL DISORDER; VOMITING; WEIGHT REDUCTION;

ADMINISTRATION, ORAL; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; FEMALE; HUMANS; MALE; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; PILOT PROJECTS; PYRIMIDINES; RISK; SALVAGE THERAPY; SEVERITY OF ILLNESS INDEX; STANDARD OF CARE; THIAZOLES; TREATMENT FAILURE;

EID: 84872980323     PISSN: 01452126     EISSN: 18735835     Source Type: Journal    
DOI: 10.1016/j.leukres.2012.11.001     Document Type: Article

References (26)

1. Prebet T., Gore S.D., Esterni B., Gardin C., Itzykson R., Thepot S., et al. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol 2011, 29:3322-3327.
2. Lin K, Reljic T, Kumar A, Lancet JE, List AF, Komrokji RS. Poor outcome of patients with myelodysplastic syndrome (MDS) after azacitidine treatment failure. ASH Annual Meeting Abstracts 2010;116:2913.
3. Jabbour E., Garcia-Manero G., Batty N., Shan J., O'Brien S., Cortes J., et al. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer 2010, 116:3830-3834.
4. Thomas S.M., Brugge J.S. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 1997, 13:513.
5. Brown M.T., Cooper J.A. Regulation, substrates and functions of src. Biochim Biophys Acta 1996, 1287:121.
6. Dos Santos C., Demur C., Bardet V., Prade-Houdellier N., Payrastre B., Recher C. A critical role for Lyn in acute myeloid leukemia. Blood 2008, 111:2269-2279.
7. Roginskaya V., Zuo S., Caudell E., Nambudiri G., Kraker A.J., Corey S.J. Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth. Leukemia 1999, 13:855-861.
8. Lannutti B.J., Blake N., Gandhi M.J., Reems J.A., Drachman J.G. Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656. Blood 2005, 105:3875-3878.
9. Ozawa Y., Williams A.H., Estes M.L., Matsushita N., Boschelli F., Jove R., et al. Src family kinases promote AML cell survival through activation of signal transducers and activators of transcription (STAT). Leuk Res 2008, 32:893-903.
10. Kantarjian H.M., Shah N.P., Cortes J.E., Baccarani M., Agarwal M.B., Undurraga M.S., et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 2012, 119:1123-1129.
11. Kantarjian H., Shah N.P., Hochhaus A., Cortes J., Shah S., Ayala M., et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010, 362:2260-2270.
12. Karaman M.W., Herrgard S., Treiber D.K., Gallant P., Atteridge C.E., Campbell B.T., et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008, 26:127-132.
13. Lombardo L.J., Lee F.Y., Chen P., Norris D., Barrish J.C., Behnia K., et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 2004, 47:6658-6661.
14. Greenberg P., Cox C., LeBeau M.M., Fenaux P., Morel P., Sanz G., et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997, 89:2079-2088.
15. Cheson B.D., Greenberg P.L., Bennett J.M., Lowenberg B., Wijermans P.W., Nimer S.D., et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006, 108:419-425.
16. Verstovsek S., Tefferi A., Cortes J., O'Brien S., Garcia-Manero G., Pardanani A., et al. Phase II study of dasatinib in philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res 2008, 14:3906-3915.
17. Corey S.J., Shapiro D.N. Localization of the human gene for Src-related protein tyrosine kinase LYN to chromosome 8q11-12: a lymphoid signaling cluster?. Leukemia 1994, 8:1914-1917.
18. Haase D., Germing U., Schanz J., Pfeilstocker M., Nosslinger T., Hildebrandt B., et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007, 110:4385-4395.
19. Sekeres M.A., Schoonen W.M., Kantarjian H., List A., Fryzek J., Paquette R., et al. Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst 2008, 100:1542-1551.
20. Schanz J., Tuchler H., Sole F., Mallo M., Luno E., Cervera J., et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol 2012, 30:820-829.
21. Wolman S.R., Gundacker H., Appelbaum F.R., Slovak M.L. Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest oncology group study. Blood 2002, 100:29-35.
22. Byrd J.C. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from cancer and leukemia group B (CALGB 8461). Blood 2002, 100:4325-4336.
23. Slovak M.L., Kopecky K.J., Cassileth P.A., Harrington D.H., Theil K.S., Mohamed A., et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest oncology group/Eastern cooperative oncology group study. Blood 2000, 96:4075-4083.
24. Schoch C., Kohlmann A., Dugas M., Kern W., Schnittger S., Haferlach T. Impact of trisomy 8 on expression of genes located on chromosome 8 in different AML subgroups. Genes Chrom Cancer 2006, 45:1164-1168.
25. Schoch C., Kohlmann A., Dugas M., Kern W., Hiddemann W., Schnittger S., et al. Genomic gains and losses influence expression levels of genes located within the affected regions: a study on acute myeloid leukemias with trisomy 8, 11, or 13, monosomy 7, or deletion 5q. Leukemia 2005, 19:1224-1228.
26. Virtaneva K., Wright F.A., Tanner S.M., Yuan B., Lemon W.J., Caligiuri M.A., et al. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci USA 2001, 98:1124-1129.