Managed Care - July 2008 - (Page H8) 75 mg/m2/day for 5 days, followed by 2 days of no treatment and then 2 additional days of 75 mg/m 2/day (n=50). The third regimen, AZA-5-2-5, consisted of azacitidine 50 mg/m2/day for 5 days, followed by 2 days of no treatment and then 5 additional days at the 50 mg/m2/day dose (n=51). Hematologic improvements in all groups were comparable to those obtained with a 7-day schedule. TI was achieved in 16, 12, and 12 patients in the AZA-5, AZA-5-2-2, and AZA-5-2-5 arms, respectively. Approximately 63 percent of patients who were transfusion dependent at baseline achieved TI with treatment. No new adverse effects were reported with these alternative-dosing regimens; their efficacy and tolerability suggest that clinicians may have flexibility in designing new treatment regimens without weekend dosing. Decitabine. Decitabine is another agent that strongly inhibits DNA methylation and has been proven to be clinically effective in patients with MLS (Saba 2005). Decitabine also is capable of inducing cell differentiation and has led to cytogenetic conversion in approximately 30 percent of patients (Lübbert 2001). In high-risk patients, response rates have been as high as 64 percent, and with regard to overall response rates, decitabine appears to exhibit efficacy comparable to that of azacitidine (Saba 2005). The FDA has approved decitabine for use as an intravenous agent only in a hospital setting. However, as with azacitidine, alternative-dosing regimens have evolved over time in clinical practice. Some alternative regimens, such as using lower doses in an outpatient setting, have been evaluated in randomized trials. For example, Kantarjian (2007) has demonstrated optimal results with a 1-hour, 5-day schedule of decitabine use in an outpatient setting. As with azacitidine, longer treatment did not result in improved rates of survival. Conclusion Just a decade ago, patients with MDS had few treatment options outside of supportive care and transfusions. Today, an expanding list of approved agents, including erythropoietins (EPO and darbepoetin alfa), myeloid growth factors, such as G-CSF and GM-CSF, the hypomethylating agents decitabine and azacitidine, and lenalidomide have increased the rational treatment options available. With a considerable number of new agents demonstrating efficacy in phase 1 and 2 clinical trials, it is likely that some of the currently unmet needs among patients with MDS will be addressed in the coming years. Cheson BD, Bennett JM, Kantarjian H, et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000;96:3671–3674. Fenaux P, Mufti GJ, Santini V, et al. Azacitidine treatment prolongs overall survival in higher-risk MDS patients compared with conventional care regimens: results of the AZA-001 phase III study. Blood. 2007;110:817. Frytak JR, Henk HJ, de Castro CM, et al. Cost of transfusion dependency among managed care patients with myelodysplastic syndromes. Clin Adv Hematol Oncol. 2007;5(7):7–8. Greenberg P, Cox C, LeBeau MM, et al. International scoring system (IPSS) for evaluating prognosis in myelodysplastic syndrome. Blood. 1997;89:2079–2088. Kantarjian H, Garcia-Manero G, O’Brien S, et al. Survival and efficacy of decitabine in myelodysplastic syndromes (MDS), analysis of the 5-day IV dosing regimen. Blood. 2007;110:115. List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355:1456–1465. Lübbert M, Wijermans P, Kunzman R, et al. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2’deoxycitidine. Br J Haematol. 2001;14:349–357. Lyons RM, Cosgriff T, Modi S, et al. Results of the initial treatment phase of a study of three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. Clin Adv Hematol Oncol. 2008;5(7 suppl 10):8. Mannone L, Gardin C, Quarre MC, et al. High response rate to darbepoetin alfa in “low risk” MDS: results of a phase II study. Blood. 2004;104:69a. Moyo V, Lefebvre P, Duh MS, et al. Erythroid response (ER) rates in myelodysplastic syndromes (MDS) patients treated with epoetin alfa (EPO): a meta-analysis using the International Working Group criteria (IWGc) for MDS response. J Clin Oncol. 2006 June 20 Suppl. 2006 ASCO Annual Meeting Proceedings Part I. 24(18S):6572. Mundle SD, Lefebvre P, Duh MS, et al. Erythroid response (ER) rates in myelodysplastic syndromes (MDS) patients treated with Epoetin Alfa (EPO) or Darbepoetin Alfa (DARB) using International Working Group criteria (IWGc): comparative metaanalysis. Blood. 2006;108: abstract 2672. Musto P, Lanza F, Balleari E, et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol. 2005;128:204–209. NCCN (National Comprehensive Cancer Network). NCCN Clinical Practice Guidelines in Oncology. Myelodysplastic Syndromes; v.2.2008. «http://www.nccn.org/ professionals/ physician_gls/PDF/mds.pdf.» Accessed June 2, 2008. Nimer SD. Myelodysplastic syndromes. Blood. 2008;111:4841–4851 Raza A, Reeves JA, Feldman EJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111:86–93. Saba H, Wijermans PW. Decitabine in myelodysplastic syndromes. Semin Hematol. 2005;42:S23–S31. Silverman LR, McKenzie DR, Peterson BL. 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;20:3895–3903. Stasi R, Abruzzese E, Lanzetta G, el al. Darbepoetin alfa for the treatment of anemic patients with low- and intermediate-1–risk myelodysplastic syndromes. Ann Oncol. 2005;16:1921–1927. Disclosures: Steven Coutré, MD, has received honoraria from Novartis, Celgene, and Bristol Myers Squibb, and a consulting fee from Celgene. He reports having been compensated for work related to lenalidomide (Revlimid). References American Cancer Society. Overview: myelodysplastic syndrome. 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