Intensive chemotherapy based on cytarabine combined with an anthracycline has a limited impact on the long-term overall survival for patients older than 60 years of age with acute myeloid leukemia (AML). Recently, though, encouraging results from a phase 2 trial investigating a 10-day decitabine schedule suggest that decitabine results in complete remission rates similar to those achieved with intensive chemotherapy with, however, less toxicity. EORTC trial 1301 will compare the effect this decitabine therapy has on overall survival and quality of life with that of conventional induction chemotherapy in these older patients.
There has been limited progress in the treatment of older patients with AML in decades. The “3+7” chemotherapy regimen is currently the standard of care for AML patients, but results in older patients are not as good as in younger patients. Promising results have been observed in several trials testing the efficacy of DNA-hypomethylating agents, such as decitabine, in patients with AML. These trials came on the heels of results from genetic studies that showed recurrent somatic mutations in genes involved in epigenetics.
Prof Michael Lübbert of the University Hospital Freiburg, Germany, and a coordinator of this study explains, “Treatment with hypomethylating agents such decitabine could be curative when used in a sequential approach. First one induces mild ” debulking” of the disease with the hypomethylating agent and then follows this with reduced-toxicity conditioning and allografting. In this treatment strategy, the hypomethylating agents are used as an intermediate, bridging treatment strategy prior to allografting.”
Dr Gerwin Huls of the Radboud University Medical Center, Nijmegen, The Netherlands, and a coordinator of this study says, “We think the time has come to compare conventional intensive chemotherapy, the so-called “3+7” regimen, in a randomized phase III trial with a hypomethylating agent, decitabine, to determine the optimal strategy for treating older patients with AML.”
Dr Pierre Wijermans of the HagaZiekenhuis, Den Haag, The Netherlands, and a coordinator of this study points out, “This trial will help us evaluate whether the 10-day decitabine schedule followed by reduced-toxicity conditioning and allografting or by continuation of 5-days decitabine cycles is superior to conventional intensive chemotherapy followed by reduced-toxicity conditioning and allografting in patients who have reached complete or partial remission.”
EORTC trial 1301 is an open-label, randomized, multicenter phase III, intergroup trial coordinated and sponsored by the EORTC with the collaboration of the EORTC Leukemia Group, CELG, GIMEMA, and the German MDS Study Group. GIMEMA is the representative of the Sponsor in Italy. This trial plans to enroll 600 patients at 70 sites located in ten countries: Belgium, Bulgaria, Croatia, France, Germany, Italy, Lithuania, Portugal, Slovakia, and The Netherlands. This trial is supported by an educational grant from Janssen Pharmaceuticals.
John Bean, PhD
EORTC, Medical Science Writer