Decitabine for the treatment of acute myeloid leukemia

Abstract

Introduction: Intensive chemotherapy remains the only therapeutic option that provides a reasonable chance of long-term survival for adults with acute myeloid leukemia (AML), particularly for those younger than 60 years of age. However, the vast majority of patients with AML are older than 60 years and the risks associated with intensive approaches are not only substantially greater but are also associated with significantly lower response rates. While a subset of older adults who are medically fit and have favorable biological features may be suitable candidates for intensive chemotherapy, many older adults are not candidates due to comorbidities, impaired performance status, and/or poor prognosis due to cytogenetic and molecular features. Outside of supportive care, there are limited treatment options that provide durable responses for older patients with AML, thereby warranting the development of novel therapeutic approaches. Decitabine (Dacogen, Astex/Eisai), a nucleoside analog, is FDA approved for the treatment of myelodysplastic syndrome (MDS) and has shown encouraging antileukemic efficacy for the management of older adults with AML. Combined with its favorable side-effect profile, decitabine has been at the center of several trials in the treatment of older adults with AML. Furthermore, decitabine is approved for the treatment of elderly AML in Europe.Areas covered: This paper will discuss the biological and clinical rationale for using decitabine as frontline therapy for AML patients unable to tolerate and/or benefit from intensive chemotherapy. A review of selected published manuscripts and abstracts on the subject of elderly AML and a search of PubMed for manuscripts in English using a combination of index words including AML, decitabine, elderly, hypomethylation, and 2′-deoxy-5-azacytidine was conducted and articles of interest selected.Expert opinion: Conventional treatment strategies for AML have not changed appreciably over the last 40 years. The intensive strategies necessary for attaining long-term survival are best tolerated by individuals younger than 60 – 65 years of age and a subset of medically fit older adults with favorable biological features. Unfortunately, many older adults with AML are medically unfit for intensive therapy due to significant comorbidities or poor functional status. In this setting, epigenetic therapy with hypomethylating agents represents a reasonable approach for the frontline treatment of older patients with AML unwilling or unsuitable for intensive chemotherapy or clinical trial. Decitabine has proven clinical benefits for patients with MDS and more recently in patients with AML. Response rates gained from low-dose decitabine (20 mg/m2 i.v. daily for 5 or 10 days every 28 days) are comparable to more intensive strategies. Compared to other widely accepted low-intensity programs such as low-dose cytarabine (20 mg/m2 subcutaneously once daily for 10 days) and supportive care, the 5-day decitabine regimen provides a modest survival benefit, as well.