Decitabine Shows Promise as Treatment for Elderly Acute Myeloid Leukemia Patients

It is a hypomethylating agent that reduces labeling of DNA with methyl groups by inhibiting DNA methyltransferase. Excess methyl labeling of DNA that silences tumor suppressing genes has been linked to cancer development.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) treated fifty-five patients (mean age, 74 years) with decitabine intravenously for five consecutive days of a four-week cycle. Response to the drug was assessed by weekly CBC (complete blood count) and bone marrow biopsy after cycle two and after each subsequent cycle. Patients continued to receive decitabine until disease progression or an unacceptable adverse event occurred.

Results published in the December 21, 2009, online edition of the Journal of Clinical Oncology revealed that in 24% of the patients, blood counts and bone marrow returned to normal. An average of 4.5 cycles of decitabine treatment was required to attain this complete response. In those with a complete response, average survival time was 14 months. For all study participants, average survival time was 7.7 months.

Treatment-related adverse events included low blood counts (red cells, white cells, and platelets), infection, fever, and fatigue. Almost half of the study participants had at least one serious adverse event. Seven patients discontinued treatment, and three patients died as the result of adverse events.

"Older leukemia patients do not have good treatment options because the chemotherapy and stem cell transplants that we commonly use for younger patients are often too toxic for them," explained first author Dr. Amanda F. Cashen, assistant professor of medicine at the Washington University School of Medicine. "Furthermore, the biology of acute leukemia in the older patient population is different, making their response rate lower, their risk of relapse higher and their cure rates lower. So we definitely need new therapies in that patient population -treatments that are going to be both better tolerated and more effective."

"We have to wait for the results of further trials of decitabine to have a better estimate of the response rate and survival outcome compared to other low intensity options for older adults," said Dr. Cashen. "This study can not definitively establish decitabine's role for treating older adults with AML, but it certainly excites us to study it more."

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Washington University School of Medicine