INTRODUCTION: Older patients with acute myeloid leukemia (AML) are often unsuitable for standard treatments and traditionally have a dismal prognosis. For 20 years, hypomethylating agents (HMAs), as single agents and recently as a backbone with venetoclax, have been used in this setting. The oral combination of decitabine and cedazuridine (C-DEC), which is therapeutically and pharmacologically equivalent to the intravenous (IV) formulation (IV-DEC), has expanded the therapeutic arsenal for AML, allowing for better convenience of administration. This review provides an overview of C-DEC, current clinical applications, and ongoing clinical studies, highlighting its potential role in managing AML in older patients.

AREAS COVERED: For the aim of this review, the authors searched the current English literature on C-DEC in AML patients through PubMed, using several pertinent keywords. To summarize the most recent developments as up-to-date as possible, we considered, with a few exceptions, only papers published over the last three years until March 2025.

EXPERT OPINION: Compared to IV-DEC, C-DEC provides similar therapeutic exposure and efficacy with an optional safety profile, enhanced treatment adherence, reduced treatment burden, and required healthcare facilities compared to those associated with IV-DEC, providing a precious tool to manage older and unfit AML patients.