Dacogen (decitabine) is a new drug, a DNA methyltransferase inhibitors (DMTI) that approved by the FDA for use in all French- American British (FAB) categories for MDS. The response rates for Dacogen were 30% (9% CR, 8% PR, 13% HI). Median TTP was prolonged from 7.8 months to 12.1 months compared to supportive care (p=0.1). Higher response rates have been reported in a single institution trial using lower doses of Dacogen. This drug is now FDA approved for MDS.
For acute meulogenous leukemia, less is known. A 2007 review, looked at 33 patients. with the WHO criteria of AML that were treated with decitabine alone (23 patients) or in combination with valproic acid (10 patients) as first-line therapy. There were 20 men (61%) and their median age was 72, range 39 to 85. Median bone marrow blasts at study entry was 26%, and 14 (42%) had >30% blasts. There were three different schedules of decitabine IV, which gave a total of 100–150 mg/m2/course over 3–10 days. Of the 33 patients treated, there were 8 CRs (24%) and 9 marrow CR/PR/Hematologic improvement (27%) for a total response rate of 17 (52%). Overall mortality at 4 weeks and 8 weeks was 3% and 15%, respectively. At a median follow-up of 20 months, median survival of the entire group was 12.6 months (95% CI: 6.5–23.0), and 2-year survival was 25% (95% CI: 13–48), which compares favorably to reported AML survival in this age group in the United States. The study concluded that decitabine is an effective and less toxic treatment in this AML age group and may prolong survival compared with supportive care.
NCCN(p. AML-11) lists it along with other drugs for induction therapy for patients older than 60.
In 2011, ASCO, a phase III study was presented. Xavier G. Thomas, MD, from the Hospital Edouard Herriot, Lyon, France, and colleagues performed a randomized, controlled, open-label trial that enrolled 485 patients with poor- or intermediate-risk cytogenetics, and ECOG PS 0–2. They were randomized to either supportive care (n=28) or 20mg/m2 AraC SQ once daily for 10 consecutive days, every 4 weeks (n=215) or DAC 20mg/m2 as a 1-hour IV infusion once daily for 5 consecutive days, every 4 weeks (n=242). An updated unplanned OS analysis with 446 (92%) deaths showed the same median survival with strengthened, albeit nominal evidence of the DAC effect (P=0.037) (0.82, 95%CI [0.68–0.99]). The secondary endpoint of complete remission (CR) + complete remission in the absence of total platelet recovery (CRp) rate was 17.8% (DAC) versus 7.8% (SC) with overall response (CR + CRp + partial response) of 2.5 (P=0.001). Safety rates were consistent with the known DAC safety profile and without major differences between the treatment arms.
Silverman L, Demakos E, Peterson B, et L. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J. Clin. Oncol 2002; 10: 2241-2252.
Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.
Data from DACO-016 study at 2011 American Society of Clinical Oncology Annual Meeting
Kantarjian H, O’Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.