Multicenter Study of Decitabine Administered Daily for 5 Days Every 4 Weeks to Adults With Myelodysplastic Syndromes: The Alternative Dosing for Outpatient Treatment (ADOPT) Trial

Abstract

Purpose Decitabine, a DNA-targeted hypomethylating agent, is approved by the United States Food and Drug Administration for treatment of patients with myelodysplastic syndromes (MDS) on a schedule of 15 mg/m2 administered via intravenous (IV) infusion every 8 hours for 3 days. This study assessed the efficacy and safety of an alternative dosing regimen administered on an outpatient basis in academic and community-based practices. Patients and Methods Patients were treated with decitabine 20 mg/m2 by IV infusion daily for 5 consecutive days every 4 weeks. Eligible patients were ≥ 18 years of age and had MDS (de novo or secondary) of any French-American-British (FAB) subtype and an International Prognostic Scoring System (IPSS) score ≥ 0.5. The primary end point was the overall response rate (ORR) by International Working Group (IWG 2006) criteria; secondary end points included cytogenetic responses, hematologic improvement (HI), response duration, survival, and safety. Results Ninety-nine patients were enrolled; the ORR was 32% (17 complete responses [CR] plus 15 marrow CRs [mCRs]), and the overall improvement rate was 51%, which included 18% HI. Similar response rates were observed in all FAB subtypes and IPSS risk categories. Among patients who improved, 82% demonstrated responses by the end of cycle 2. Among 33 patients assessable for a cytogenetic response, 17 (52%) experienced cytogenetic CR (n = 11) or partial response (n = 6). Conclusion Decitabine given on a 5-day schedule provided meaningful clinical benefit for patients with MDS, with more than half demonstrating improvement. This suggests that decitabine can be administered in an outpatient setting with comparable efficacy and safety to the United States Food and Drug Administration–approved inpatient regimen.

Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine

“…More recently, Cashen et al reported results of a three-institution trial of single-agent decitabine, targeting a patient population similar to that in the present study (median age in both studies was 74 years) (29). For 55 AML patients of age ≥ 60 who were not candidates for intensive therapy, the investigators administered 5 d of decitabine treatment per cycle, an approach identical to that previously published for MDS (30,31). With the 5-d approach, the CR rate was 24% and the overall response rate 25%.…”

Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome

“…for 3 days every 6 weeks, potentially higher CR rates may be obtained by administering DEC at dose/schedule of 20 mg/m 2 /day i.v. for 5 days every 28 days in other trials, 6,9 as this is the dose and schedule we employed in the current study.…”

“…3 Although DEC did not significantly extend OS, 4,5 the overall response rate to DEC among patients with highrisk MDS was 30-49%. [6][7][8][9] Lenalidomide has been reported to reduce anemia and transfusion dependence among MDS patients with a chromosome 5q deletion. 10 Although these agents have induced hematological and cytogenetic responses in a substantial portion of patients, these therapies are not curative.…”

Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of Eurocord and CLWP of EBMT

“…Patients with MDS or secondary acute myeloblastic leukemia (sAML) respond very poorly to chemotherapy and in higher risk patients, survival is below 10% at 2 years. 7-9 New medications such as demethylating agents have shown some hematological and survival improvements, [10][11][12][13] but allogeneic hematopoietic stem cell transplantation (HSCT) remains indicated in high-risk patients aged o60 years. 14- 16 Unfortunately, only 40-50% of patients will have a suitable HLA-matched donor.…”