: On September 20, 2012, a marketing authorization valid throughout the European Union (EU) was issued for
decitabine for the treatment of adult patients aged 65 years and older with newly diagnosed de novo or secondary
acute myeloid leukemia (AML) who are not candidates for standard
induction chemotherapy.
Decitabine is a
pyrimidine analog incorporated into
DNA, where it irreversibly inhibits
DNA methyltransferases through covalent adduct formation with the
enzyme. The use of
decitabine was studied in an open-label, randomized, multicenter phase III study (DACO-016) in patients with newly diagnosed de novo or secondary AML.
Decitabine (n = 242) was compared with patient's choice with physician's advice (n = 243) of low-dose
cytarabine or supportive care alone. The primary endpoint of the study was overall survival. The median overall survival in the intent-to-treat (ITT) population was 7.7 months among patients treated with
decitabine compared with 5.0 months for those in the control arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.04; p = .1079). Mature survival data after an additional year of follow-up were consistent with these results, with a median overall survival of 7.7 months in patients treated with
decitabine and 5.0 months in the control arm (HR, 0.82; 95% CI, 0.68-0.99; p = .0373). Secondary endpoints, including response rates, progression-free survival, and event-free survival, were increased in favor of
decitabine when compared with control treatment. The most common
adverse drug reactions reported during treatment with
decitabine are
pyrexia,
anemia,
thrombocytopenia,
febrile neutropenia,
neutropenia,
nausea, and
diarrhea. This paper summarizes the scientific review of the application leading to approval of
decitabine in the EU. The detailed scientific assessment report and product information (including the summary of product characteristics) for this product are available on the EMA website (http://www.ema.europa.eu).
IMPLICATIONS FOR PRACTICE:
Acute myeloid leukemia (AML) remains an area of significant unmet need, especially in older patients. Older patients and those with comorbidities are often considered ineligible for standard induction
therapy, and outcome for these patients is poor.
Decitabine has favorable effects in terms of overall survival, which were considered clinically meaningful in the context of a manageable toxicity profile and after consideration of the lack of therapeutic alternatives for these patients.
Decitabine is widely used in the treatment of AML in patients aged >60 years, as per current guidelines, including the European LeukemiaNet and the U.S. National
Cancer Comprehensive Network.