Safety and efficacy of azacitidine in the treatment of elderly patients with myelodysplastic syndrome

Clinical Interventions in Aging

Volumn 7, Issue , 2012, Pages 165-173

  Ritchie, Ellen K ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Acute myeloid leukemia; Azacitidine; Geriatrics; Myelodysplastic syndrome; Supportive care

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ALLOPURINOL; ANTIDIARRHEAL AGENT; ANTIEMETIC AGENT; ANTIHISTAMINIC AGENT; AZACITIDINE; CORTICOSTEROID; CYTARABINE; FUROSEMIDE; GENTAMICIN; GRANULOCYTE COLONY STIMULATING FACTOR; LAXATIVE; LENALIDOMIDE; LEVOFLOXACIN; MESSENGER RNA; ONDANSETRON; PARACETAMOL; PIPERACILLIN PLUS TAZOBACTAM; PLACEBO; ROMIPLOSTIM; THROMBOPOIETIN; VANCOMYCIN; ANTINEOPLASTIC ANTIMETABOLITE;

ACUTE GRANULOCYTIC LEUKEMIA; AGE; ALLOGENEIC STEM CELL TRANSPLANTATION; ANEMIA; CANCER MORTALITY; CHROMOSOME ABERRATION; CHRONIC DRUG ADMINISTRATION; CLINICAL EFFECTIVENESS; CLINICAL TRIAL (TOPIC); COMORBIDITY; CONSTIPATION; CYTOPENIA; DIARRHEA; DISEASE ASSOCIATION; DOSAGE SCHEDULE COMPARISON; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG FEVER; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; ERYTHEMA; EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER QUALITY OF LIFE QUESTIONNAIRE C30; FATIGUE; FEASIBILITY STUDY; FEBRILE NEUTROPENIA; HEALTH CARE MANAGEMENT; HEALTH STATUS; HIGH RISK POPULATION; HUMAN; INFECTION; INJECTION SITE REACTION; LOW DRUG DOSE; LOW RISK POPULATION; MENTAL HEALTH INVENTORY; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PANCYTOPENIA; PATIENT CARE; QUALITY OF LIFE; REVIEW; SURVIVAL RATE; THROMBOCYTE COUNT; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; TREATMENT OUTCOME; VOMITING; AGED; DISEASE COURSE; DRUG SCREENING; GENETICS; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; RISK ASSESSMENT; SICKNESS IMPACT PROFILE;

AGE FACTORS; AGED; ANTIMETABOLITES, ANTINEOPLASTIC; AZACITIDINE; CHROMOSOME ABERRATIONS; CYTARABINE; DISEASE PROGRESSION; DRUG EVALUATION; HUMANS; LEUKEMIA, MYELOID, ACUTE; MYELODYSPLASTIC SYNDROMES; OUTCOME ASSESSMENT (HEALTH CARE); QUALITY OF LIFE; RISK ASSESSMENT; SICKNESS IMPACT PROFILE;

EID: 84869872832     PISSN: 11769092     EISSN: 11781998     Source Type: Journal    
DOI: 10.2147/CIA.S24659     Document Type: Review

References (49)

1. United States Cancer Statistics: 1999-2007incidence and mortality web-based report. Atlanta, GA: Centers for Disease Control and Prevention. Available from: http://apps.nccd.cdc.gov/uscs/. Accessed April 16, 2012.
2. Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007;109(8):1536-1542.
3. US Census Bureau Current Population Reports. 1193.
4. Steensma DP, Heptinstall KV, Johnson VM, etal. Common troublesome symptoms and their impact on quality of life in patients with myelodysplastic syndromes (MDS): results of a large Internet-based survey. Leuk Res. 2008;32(5):691-698.
5. Jansen AJ, Essink-Bot ML, Beckers EA, Hop WC, Schipperus MR, Van Rhenen DJ. Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes. Br J Haematol. 2003;121(2): 270-274.
6. Platzbecker U, Hofbauer LC, Ehninger G, Holig K. The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes. Leuk Res. January 31, 2012. [Epub ahead of print.]
7. Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, etal. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120(6): 1037-1046.
8. Seymour JF, Fenaux P, Silverman LR, etal. Effects of azacitidine compared with conventional care regimens in elderly ($75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol. 2010;76(3):218-227.
9. Sekeres MA, Schoonen WM, Kantarjian H, etal. Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst. 2008;100(21):1542-1551.
10. Burnett AK, Milligan D, Prentice AG, etal. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007;109(6): 1114-1124.
11. Shih AH, Levine RL. Molecular biology of myelodysplastic syndromes. Semin Oncol. 2011;38(5):613-620.
12. Greenberg P, Cox C, LeBeau MM, etal. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6): 2079-2088.
13. Jiang Y, Dunbar A, Gondek LP, etal. Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood. 2009;113(6): 1315-1325.
14. Ward AJ, Cooper TA. The pathobiology of splicing. J Pathol. 2010; 220(2):152-163.
15. Yoshida K, Sanada M, Shiraishi Y, etal. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367): 64-69.
16. Visconte V, Makishima H, Jankowska A, etal. SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia. 2012;26(3):542-545.
17. Papaemmanuil E, Cazzola M, Boultwood J, etal. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011;365(15):1384-1395.
18. Damm F, Kosmider O, Gelsi-Boyer V, etal. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood. 2012;119(14):3211-3218.
19. Jadersten M, Saft L, Smith A, etal. TP53mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 2011;29(15):1971-1979.
20. Ko M, Huang Y, Jankowska AM, etal. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839-843.
21. Jankowska AM, Makishima H, Tiu RV, etal. Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. Blood. 2011;118(14):3932-3941.
22. Harries LW, Hernandez D, Henley W, etal. Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing. Aging Cell. 2011;10(5):868-878.
23. Forsberg LA, Rasi C, Razzaghian HR, etal. Age-related somatic structural changes in the nuclear genome of human blood cells. Am J Hum Genet. 2012;90(2):217-228.
24. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, etal. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223-232.
25. Kantarjian H, Issa JP, Rosenfeld CS, etal. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794-1803.
26. Lubbert M, Suciu S, Baila L, etal. Low-dose decitabine versus best supportive care in elderly patients with intermediate-or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29(15): 1987-1996.
27. Steensma DP, Baer MR, Slack JL, etal. Multicenter study of decitabine administered daily for 5days every 4 weeks to adults with syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27(23):3842-3848.
28. Kantarjian H, Oki Y, Garcia-Manero G, etal. Results of a randomized study of 3schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007;109(1):52-57.
29. Silverman LR, McKenzie DR, Peterson BL, etal. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006;24(24):3895-3903.
30. Kornblith AB, Herndon JE 2nd, Silverman LR, etal. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002;20(10):2441-2452.
31. Itzykson R, Thepot S, Quesnel B, etal. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403-411.
32. Fenaux P, Gattermann N, Seymour JF, etal. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. Br J Haematol. 2010;149(2): 244-249.
33. Kantarjian H, O'Brien S, Cortes J, etal. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106(5):1090-1098.
34. Marcucci G, Silverman L, Eller M, Lintz L, Beach CL. Bioavailability of azacitidine subcutaneous versus intravenous in patients with the myelodysplastic syndromes. J Clin Pharmacol. 2005;45(5):597-602.
35. Lyons RM, Cosgriff TM, Modi SS, etal. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009;27(11):1850-1856.
36. Garcia R, de Miguel D, Bailen A, etal. Different clinical results with the use of different dosing schedules of azacitidine in patients with myelodysplastic syndrome managed in community-based practice: effectiveness and safety data from the Spanish azacitidine compassionate use registry (Abstract 2773). Blood. 2009;144(22).
37. Garcia-Manero G, Gore SD, Cogle C, etal. Phase I study of oral azacitidine in myelodysplastic sydromes, chronic myelomonocytic leukemia and acute myeloid leukemia. J Clin Oncol. 2011;29(18):2521-2527.
38. Silverman LR, Demakos EP, Peterson BL, etal. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2002;20(10):2429-2440.
39. Santini V, Fenaux P, Mufti GJ, etal. Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*. Eur J Haematol. 2010;85(2):130-138.
40. Itzykson R, Thepot S, Beyne-Rauzy O, etal. Does addition of erythropoiesis stimulating agents improve the outcome of higher-risk myelodysplastic syndromes treated with azacitidine? Leuk Res. 2011;36(4):397-400.
41. Kantarjian HM, Giles FJ, Greenberg PL, etal. Phase 2study of romiplostim in patients with low-or intermediate-risk syndrome receiving azacitidine therapy. Blood. 2010;116(17):3163-3170.
42. List A, Kurtin S, Roe DJ, etal. Efficacy of lenalidomide in syndromes. N Engl J Med. 2005;352(6):549-557.
43. List A, Dewald G, Bennett J, etal. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355(14): 1456-1465.
44. Musto P, Maurillo L, Spagnoli A, etal. Azacitidine for the treatment of lower risk myelodysplastic syndromes: a retrospective study of 74 patients enrolled in an Italian named patient program. Cancer. 2010;116(6):1485-1494.
45. Grovdal M, Karimi M, Khan R, etal. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010;150(3): 293-302.
46. Braiteh F, Soriano AO, Garcia-Manero G, etal. Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin Cancer Res. 2008;14(19):6296-6301.
47. Sekeres MA, List AF, Cuthbertson D, etal. Phase I combination trial of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes. J Clin Oncol. 2010;28(13): 2253-2258.
48. Sekeres MA, O'Keefe C, List AF, etal. Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher-risk myelodysplastic syndromes. Am J Hematol. 2011;86(1):102-103.
49. Pollyea DA, Kohrt HE, Gallegos L, etal. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia. October 28, 2011. [Epub ahead of print.]