MGI Pharma, Inc, and SuperGen, Inc, recently announced that the US Food and Drug Administration (FDA) has approved the hypomethylating agent decitabine (Dacogen) for injection. Decitabine is indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo, and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System (IPSS) groups.

"The FDA approval of Dacogen marks an important advancement for patients who suffer from MDS," said John M. Bennett, MD, chair of The Myelodysplastic Syndromes Foundation. "Patients with this serious condition are often anemic, experience fatigue and weakness, and in certain cases with an increase in leukemic blast cells, MDS can result in bone marrow failure."

Clinical Findings

Results from a phase III clinical trial demonstrated an overall response rate of 21% in decitabine-treated patients considered evaluable for response, (defined as patients with pathologically confirmed MDS at baseline who received at least two cycles of treatment), compared to 0% in the supportive care arm. All patients who responded to decitabine treatment became or remained transfusion-independent during the time of the response. The most commonly occurring adverse reactions with decitabine include neutropenia, thrombocytopenia, anemia, pyrexia, fatigue, nausea, cough, petechiae, constipation, and diarrhea. It is recommended that patients be treated with decitabine for a minimum of four cycles, and treatment may continue as long as the patient continues to benefit.

SuperGen conducted a randomized open-label, multicenter, controlled trial evaluating 170 adult patients with MDS meeting FAB classification criteria and IPSS high-risk, intermediate-2 and intermediate-1 prognostic scores. Eighty-nine patients were randomized to decitabine therapy plus supportive care, 83 of whom received decitabine, and 81 were randomized to supportive care alone. Decitabine was intravenously infused at a dose of 15 mg/m2 over a 3-hour period, every 8 hours, for 3 consecutive days. Decitabine therapy was repeated every 6 weeks, depending on the patient's clinical response and toxicity. Supportive care consisted of blood and blood product transfusions, prophylactic antibiotics, and hematopoietic growth factors. Primary end points of the study were overall response rate (complete responses plus partial responses) and time to acute myeloid leukemia (AML) or death. Secondary end points included hematologic improvement, duration of response, cytogenetic response rate, transfusion requirements, quality of life, survival, and safety.

The overall response rate in the decitabine study arm was 17%, with a median response duration of 288 days, compared to 0% in the supportive care arm (P < .001). A complete response rate of 9% and a partial response rate of 8% were observed in the decitabine arm. The overall response rate was 21% in decitabine-treated patients considered evaluable for response, defined as patients with pathologically confirmed MDS at baseline who received at least two cycles of treatment. In addition, 13% of patients in the decitabine arm had hematologic improvement, compared to 7% of patients in the supportive care arm.

Additional Data

Two additional open-label, single-arm, multicenter studies were conducted to evaluate the safety and efficacy of decitabine in patients with MDS of any FAB subtype. The results of the phase II studies were consistent with the results of the phase III trial, with overall response rates of 26% (N = 66) and 24% (N = 98).

"Dacogen represents a new treatment option that can reduce or eliminate the need for patients with MDS to receive frequent blood transfusions, which is an important clinical benefit," said Hagop Kantarjian, MD, professor and chairman, Department of Leukemia, at the University of Texas M.D. Anderson Cancer Center, and clinical investigator of the ongoing decitabine clinical development program for MDS and AML. "This approval is a major advance in our fight against myelodysplastic syndromes."