Drug that switches on genes improves myelodysplastic syndrome treatment

A potent member of a new class of drugs increases survival in some patients with myelodysplastic syndrome (MDS), and may become the new standard of therapy for this group of pre-cancer disorders, say researchers at The University of Texas M. D. Anderson Cancer Center who led a national study of the agent.

The drug, decitabine, is designed to turn on genes that cancer had switched off, and in this study, patients who were treated with it achieved a significantly higher overall response rate, compared to patients receiving supportive care, which includes transfusions of red blood cells and platelets.

Results of the randomized Phase III clinical trial, published March 13, 2006 in the online version of the journal Cancer, also concluded that in treated patients who responded to the drug, the median time to progression of the disease, or death, was 17.5 months, compared to 9.8 months in patients who did not.

"This is a very promising drug that we believe works even better when patients use it for a period that is longer than that tested in this trial," says lead author, Hagop Kantarjian, M.D., chair of the Department of Leukemia at M. D. Anderson.

For example, interim analysis of an ongoing study demonstrated a 40 percent complete response rate when the drug was given in lower doses over a longer period of time, said Kantarjian, who presented these results in December 2005, at the annual meeting of the American Society of Hematology. In contrast, the 83 patients treated with decitabine in this study received comparatively fewer rounds of therapy, and the response rate was 17 percent, he said.

"The data suggest to us that prolonged treatment is important for response but the optimal schedule for using decitabine is being studied," said Kantarjian.

Still, he says a significant response rate represents "a vast improvement" in the care of these pre-cancers, which are a group of diseases in which the bone marrow progenitor cells that normally morph into red and white blood cells and platelets, fail to respond to normal growth controls. That results in too many progenitor cells (also known as blasts) and too few mature blood cells, and in about 30 percent of patients, the disease progresses to acute myeloid leukemia (AML). About three-fourths of MDS patients succumb to either MDS or to AML within about 2-3 years from diagnosis.

MDS is difficult to treat, especially since it usually strikes the elderly. Ten years ago, there was little to offer patients other than blood transfusions and supportive care, Kantarjian says, and newer treatments, which include the use of stem cell transplants, are not for every patient.

Decitabine is a "biological disease modifier" that was given fast-track approval by the Food and Drug Administration in April 2003.

It is a DNA hypomethylating agent that fights cancer by reversing a chemical process (methylation) that turns off tumor-suppressor genes that protect cells from becoming cancerous. Methylation is the gradual addition of chemical units known as methyl groups to genes, and as these groups accumulate, the gene gradually shuts down. Decitabine prevents the methylation process, enabling the gene to become active again.

In addition to increased survival and time-to-progression in some patients, decitabine improved quality of life in patients who responded and eliminated the need for frequent transfusions, Kantarjian said.

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Other institutions that participated in the study were The University of Rochester Medical Center, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Roswell Park Cancer Institute, Duke University Medical Center, University of Illinois, Southwest Regional Cancer Center, Rush Medical Center, and H. Lee Moffitt Cancer Center.

The study was funded by Supergen Inc., which developed decitabine.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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