Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia

Abstract

PurposeThis prospective phase II, open label, study was designed to assess the efficacy and safety of D-CAG induction treatment for elderly patients with newly diagnosed AML.Experimental DesignAll patients in this study were treated with decitabine of 15 mg/m2 for 5 days and G-CSF for priming, in combination with cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days (D-CAG).ResultsAmong 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of therapy. The ORR in patients aged <70 years was 83.0% and 81.6% in patients aged ≥70 years. There was a significantly longer median overall survival (OS) in patients with response (16 months) than in those without response (7 months, p< 0.0001). The OS for patients aged ≥70 years and 60-69 years was 10 months and 12 months, respectively (p=0.4994). The two-year OS probability was 19.2% and the twenty-month survival rate was 33.8%. Induction mortality of D-CAG treated elderly patients with AML is 4.4%.ConclusionD-CAG regimen was well tolerated and showed a promising clinic efficacy in elderly patients with AML (≥70 years).

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

“…The results revealed increased response rate and prolonged survival in patients treated with decitabine priming prior to low-dose chemotherapy compared with those treated with chemotherapy alone. Consistent with the results of previous clinical trials (Lee et al 2011; Li et al 2015; Song et al 2012), the median OS of patients achieving CR in the current study was significantly longer than that of patients with non-CR regardless of the treatment (decitabine priming or chemotherapy alone). A subgroup analysis in the current study showed a higher CR (65.5%) with a longer OS (22.4 months) in patients at <60 years of age in the decitabine priming group.…”

“…In a previous study from our research group, decitabine followed by idarubicin produced synergistic anti-leukemia effects in both cultured cells and xenograft animal models (Li et al 2014). Clinical studies that examined the combination of decitabine and chemotherapeutics, such as standard DA (daunomycin and cytarabine), low-dose AA, and CAG (G-CSF and low-dose AA) suggested CR rate at 50–60% and OR rate at 60–90% in AML and MDS/AML (Li et al 2015; Scandura et al 2011; Song et al 2012). In a previous study (Ye et al 2016), we reported a CR rate of 43% in MDS, 75% in MDS/AML and 29% in relapsed/refractory AML.…”

“…Previous studies suggested that decitabine monotherapy is a better choice for MDS patients with poor karyotypes (Li et al 2013; Lubbert et al 2001; Wu et al 2016). Several studies showed that decitabine in combination with CAG could achieve 50–70% CR in AML and MDS patients with complex karyotypes (Gao et al 2015; Li et al 2015). Gao et al also noted an association of treatment response with the number of courses in AML and MDS patients with complex karyotypes (Gao et al 2015).…”

“…In patients receiving decitabine monotherapy, the rate of CR and overall response (OR) has been reported to be 13–39 and 32–70%, respectively (Iastrebner et al 2010; Kantarjian et al 2007a, c; Lee et al 2011; Oki et al 2012; Steensma et al 2009). Decitabine in combination with a variety of agents, including histone deacetylase inhibitors, thalidomide, and conventional chemotherapeutics, has been developed to treat intermediate- and high-risk MDS and AML (Blum et al 2007; Daver et al 2016; Gao et al 2015; Garcia-Manero et al 2006; Geng et al 2016; Jiang et al 2015; Kirschbaum et al 2014; Li et al 2015; Song et al 2012; Yang et al 2005; Zhao et al 2015). Several studies showed that decitabine in combination with chemotherapy improved the outcomes in patients with relapsed/refractory AML or AML transformed from MDS (MDS/AML) (Leonard et al 2014; Li et al 2015; Scandura et al 2011; Song et al 2012).…”

Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia

“…Approval of DAC in the European Union in 2012 for the treatment of ≥65-year-old patients with AML marks the potential for hypomethylating agents in elderly AML patients. Recent studies using DAC before G-CSF, low-dose cytarabine, and aclarubicin, or before full-dose cytarabine and daunorubicin have reported encouraging results [15,16,17]. It has been shown that DAC followed by low-dose idarubicin/cytarabine (D-IA) has an increased antileukemia effect compared to traditional chemotherapy [18].…”