The MDS Beacon™

Researchers from the M.D. Anderson Cancer Center in Houston presented a Phase 2 study at the 45th meeting of the American Society for Clinical Oncology (ASCO) showing that Zolinza (vorinostat) in combination with idarubicin (Idamycin) and high-dose cytarabine (Cytosar-U) is effective as front-line therapy for high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients.

This study showed the triple combination to be safe, as patients did not experience any severe or life-threatening side effects.

There were 22 patients enrolled in the study; of these, three relapsed/refractory AML patients of the 22 initially underwent a pre-clinical trial testing the safety of the combination therapy. Two achieved complete response achieved complete response as measured by the 2000 International Working Group (IWG) criteria. 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. One patient showed minimal symptoms of MDS, though not to the extent as complete response patients.

Seventeen patients, median age 49, then underwent the Phase 2 trial. The median white blood cell count was 12.75 × 109/L at the beginning of the trial, while examination of DNA showed abnormalities in 71 percent of participants. In addition, 47 percent of participants had a secondary disease.

The untreated intermediate-2 or high-risk MDS or AML patients with adequate renal and liver functions were given 500 mg of Zolinza for three days, then both idarubicin (12 mg/m2) and cytarabine (1.5 g/m2) on the fourth. Five cycles of 500 mg of Zolinza with 8 mg/m2 of idarubicin and 0.75 g/m2 of cytarabine over 24 hours was then administered to patients with a complete response. This was followed by one year of maintenance with Zolinza.

Results showed 82 percent of patients achieved complete response, which was associated with decreased chromosomal abnormalities. However, two patients died during induction and two relapsed within four to five months. A median progression-free survival rate has not yet been observed.

Histone deacetylase inhibitors like Zolinza have been shown to work cooperatively with anthrayclines like idarubicin in therapies for MDS. Cytarabine is a chemotherapy agent that keeps the body from producing excess DNA.

Researchers plan to compare the results of this study with a parallel cytarabine study also being conducted at the M.D. Anderson Cancer Center to see how it enhances MDS treatments. Further studies are also investigating DNA damage and repair pathways.

For more information, please see abstract 7004 on the 2009 ASCO meeting Web site.