The MDS Beacon™

On May 29 at the 45th meeting of the American Society for Clinical Oncology (ASCO), researchers from the M.D. Anderson Cancer Center in Houston reported their review of randomized Phase 2 and Phase 3 trials comparing different dosing schedules of Dacogen (decitabine) in myelodysplastic syndromes (MDS) patients. Researchers found that increased numbers of treatment cycles are beneficial for MDS patients.

The Phase 3 trial participants (D-0007 and EORTC-06011) were given 15 mg/m2 intravenously over three hours every eight hours for three days every six weeks with supportive care. Phase 2 trial participants (DACO-020 and ID03-0180) were given 20 mg/m2 intravenously over one hour once daily for five consecutive days every four weeks without supportive care.

In the three-day regimen Phase 3 trials, a median of three Dacogen treatment cycles were administered to the D-0007 group, while the EORTC-06011 patients were given four cycles. Thirteen percent of patients who received four cycles achieved complete response as measured by the 2000 International Working Group (IWG) criteria, compared to only nine percent of the group given three cycles. A complete response is defined by the IWG as having a blood count of more than 1,000 neutrophil per µL and more than 100,000 platelets per µL. Patients also have no observable symptoms after a thorough examination, though the diagnosis does not necessarily mean that MDS is fully cured or that there are no cancer cells in the body.

In addition, the one-cycle difference showed an overall improvement increase of four percent (30 percent for three cycles, 34 percent for four cycles). Dependence on blood transfusions during the clinical trial also decreased for nine percent of participants with the extra Dacogen treatment, from 32 to 23 percent. However, progression to Acute Myeloid Leukemia (AML) or death decreased from 10 to 8.8 months for the four-treatment-cycle group, as did progression-free survival and overall survival (7.3 to 6.6 months and 12.8 to 10.1 months, respectively).

Groups DACO-020 and ID03-0180 received either five or seven cycles, respectively, within a five-day regimen. Phase 2 studies showed improvement in nearly every category. The two-cycle median increase improved complete response from 15 to 37 percent and overall improvement from 43 to 65 percent. In addition, time to AML progression or death was lengthened from 12.1 to 15.2 months, and progression-free and overall survival also increased from 8.1 to 9.2 months and 17.8 to 20.3 months, respectively.

The duration of improvement ranged between 9.2 and 11.3 months in all four trials.

Researchers correlate the 30 percent overall improvement rate by IWG criteria to the increased number of Dacogen treatment cycles.

For more information, please see abstract 7011 on the 2009 ASCO meeting Web site.