Decitabine improves patient outcomes in myelodysplastic syndromes

Mar 14 2006

Decitabine, a new drug undergoing Phase III efficacy trials, provides palliative therapy for patients with the bone marrow disease called Myelodysplastic Syndrome (MDS), according to a new study.

Published in the April 15, 2006 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that decitabine provided longer disease-free responses compared to supportive care. While the development of decitabine and other chemotherapies is making an impact on the lives of patients with MDS, an accompanying editorial argues that these current treatments are palliative at best and will have little additional improvement in survival.

MDS is a bone marrow disease of the elderly and one of the common geriatric blood-related cancers. It causes an increasing number of dysfunctional blood cells called blasts to proliferate in the blood at the expense of normal, functional cells - i.e., red blood cells to carry oxygen; white blood cells to fight infections; and platelets to control bleeding. MDS can be a chronic progressive disease with median survival over 5 years or a rapidly progressive disease complicated by acute myeloid leukemia (AML) with survival less than 5 years.

However, because most MDS patients are elderly and have too many risk factors to undergo a bone marrow transplant, therapy is often supportive. Chemotherapy regimens used for leukemia have been used, but results are disappointing and suggest great risk to patient lives than benefit. New drugs, such as 5--azacytidine, lenalidomide, decitabine, and cytarabine, are now being tested for efficacy and safety to treat MDS. Compared to supportive care, they generally have some quality of life and survival benefits.

In the new decitabine trial published in the April 15, 2006 issue of CANCER, researchers led by Hagop Kantarjian, M.D. of the University of Texas M. D. Anderson Cancer Center in Houston, found that MDS patients from most risk-stratified groups treated with decitabine--compared to those treated with supportive care--had longer disease free periods and longer time to progression of AML or to death. Decitabine-treated patients also were more likely to have immediate disease improvements, from complete and partial responses (17 percent versus 0 percent) to limited improvements in transfusion requirements and blast burden. They also reported significant improvement in patients' quality of life.

In an editorial published in the same issue, Ayalew Tefferi, M.D. and Louis Letendre, M.D. of the Mayo Clinic in Rochester, Minnesota put this study into larger context. According to the doctors, the current study demonstrates that these new classes of chemotherapy are effective at improving quality of life, though further refinement is required just to identify populations of MDS patients that will benefit from which drugs and the duration and schedule of single or combination drug protocols. However, the drugs offer little improvement in survival.

They conclude, "decitabine would be a welcome addition to the repertoire of drugs that provide palliative benefit for selected patients with MDS." Improvement in MDS survival "awaits better understanding of the disease pathogenesis and substantial development of molecularly targeted therapy."