The MDS Beacon™

The 45th meeting of the American Society for Clinical Oncology (ASCO) provided a forum for myelodysplastic syndromes (MDS) research from the M.D. Anderson Cancer Center in Houston. At the meeting, researchers presented a study that investigated the use of hypomethylating agents Vidaza (azacitidine) and Dacogen (decitabine) for patients with decreased kidney function and concluded that both agents are effective in this patient group.

Vidaza and Dacogen are hypomethylating, or demethylating, agents that allow DNA sequences to function normally. They remove methyl groups that are bound to DNA sequences, allowing the sequences to regulate cellular growth and control cell division.

In this trial, decreased kidney function was defined as having greater than 1.5 mg/dL creatinine in the blood. Creatinine is normally filtered from the blood by the kidneys. Prior to this study, such patients were normally not treated with hypomethylating agents.

The study examined the responses of 42 patients with either MDS, chronic myelomonocytic leukemia, or acute myeloid leukemia (AML) to standard doses of Vidaza and Dacogen. Thirty-three percent of patients received Vidaza, which is normally administered by subcutaneous injection or intravenous infusion for seven consecutive days every 28 days. The remaining 67 percent received Dacogen through intravenous infusion for three consecutive days every six weeks.

Results showed that nine percent of patients achieved a complete response. According to the International Working Group, a complete response is defined as having a blood count of more than 1,000 neutrophil per µL of blood and more than 100,000 platelets per µL of blood. Although there are no longer observable symptoms of disease, this does not necessarily mean that MDS is fully cured or that there are no cancer cells still in the body. Sixty-two percent of patients had an observable, though not complete, response.

During the course of the trial, 21 percent of patients needed to delay or stop treatment with the hypomethylating agents, while 28 percent received a dose that was lower than the standard. Specifically, 58 percent of patients with more than 2 mg/dL of creatinine in their blood experienced problems with kidney and bone marrow function during the trial and were required to decrease the treatment dose. Some patients experienced therapy-related complications, including infections (36 percent) and bleeding (17 percent).

Researchers concluded hypomethylating agents such as Vidaza and Dacogen can be used in patients with MDS and AML with greater than 1.5 mg/dL of creatinine in the blood if their response rate was comparable to patients with normal kidney function. They also recognized the need for dose adjustment in some patients.

For more information, see abstract 7089 on the 2009 ASCO meeting Web site.