Guadecitabine (SGI-110): an investigational drug for the treatment of myelodysplastic syndrome and acute myeloid leukemia

Expert Opin Investig Drugs. 2019 Oct;28(10):835-849. doi: 10.1080/13543784.2019.1667331. Epub 2019 Sep 19.

Abstract

Introduction: The incidence of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is increasing with the aging population. Prognosis and overall survival (OS) remain poor in elderly patients and in those not eligible for intensive treatment. Hypomethylating agents (HMAs) have played an important role in this group of patients but their efficacy is limited. Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second-generation DNA methylation inhibitor in development for the treatment of AML and MDS. Expert opinion: Although guadecitabine did not yield improved complete remission (CR) rates and OS compared to the control arm in patients with treatment-naïve AML who were ineligible for intensive chemotherapy, subgroup analysis in patients who received ≥4 cycles of therapy demonstrated superior outcomes in favor of guadecitabine. Given its stability, ease of administration, safety profile and prolonged exposure time, guadecitabine would be the more appropriate HMA, replacing azacitidine and decitabine, to be used combination treatment regimens in patients with myeloid malignancies.

Keywords: Acute myeloid leukemia; SGI-110; guadecitabine; hypomethylating agent; myelodysplastic syndrome.

Publication types

  • Review

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / pathology
  • Prognosis
  • Survival Rate
  • Time Factors

Substances

  • Antineoplastic Agents
  • Drugs, Investigational
  • guadecitabine
  • Azacitidine