Guadecitabine may aid treatment-naive patients with acute myeloid leukemia (AML) in achieving composite complete responses (CCR), according to a study published in The Lancet Oncology.1

Hypomethylating agents have demonstrated efficacy in the treatment of AML, but the complete response rate is low and often doesn’t sustain a durable response. Guadecitabine, a next-generation hypomethylating agent, has been shown to have a longer half-life and to prolong periods of exposure more than its predecessors, and a previous clinical study demonstrated potential efficacy.

In this phase 1/2 study ( Identifier: NCT01261312), 107 treatment-naive patients with AML were randomly assigned to receive 5-day schedules of guadecitabine 60 mg/m2 or 90 mg/m2 and a 10-day schedule of guadecitabine 60 mg/m2

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At the median follow-up of 953 days, the rate of CCR did not significantly differ among the treatment arms. CCR for patients in the 5-day 60 mg/m2 arm was 54% (95% CI, 32.8-74.4), 59% (95% CI, 38.8-77.6) for patients in the 5-day 90 mg/m2 arm, and 50% (95% CI, 35.8-64.2) for patients in the 10-day schedule arm.

The most frequently reported grade 3 or worse adverse events (AE) were febrile neutropenia (61% of patients receiving 5-day schedules vs 69% of patients receiving 10-day schedules), thrombocytopenia (49% vs 42%), neutropenia (39% vs 35%), pneumonia (29% vs 37%), anemia (29% vs 23%), and sepsis (16% vs 27%). The most frequently reported AEs for 5-day and 10-day arms, respectively, were febrile neutropenia (53% vs 48%), pneumonia (27% vs 31%), and sepsis (16% vs 27%).

Twenty-three study patients died due to adverse events and 4 deaths were deemed to be treatment related. 

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Study authors recommend the 5-day guadecitabine 60 mg/m2 regimen for this patient population, and note that “a phase 3 study in this patient population is ongoing to assess guadecitabine 60 mg/m2 in a 5-day schedule versus standard of care.”


  1. Kantarjian HM, Roboz GJ, Kropf PL, et al. Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial. Lancet Oncol. 2017 Aug 24. [Epub ahead of print] doi: 10.1016/S1470-2045(17)30576-4