FDA Approval for Decitabine
- Approved for myelodysplastic syndromes
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.On May 2, 2006, the U.S. Food and Drug Administration approved decitabine for injection (Dacogen®, made by MGI Pharma, Inc.) for the treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British 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 groups.
Safety and efficacy were demonstrated in an open-label, multicenter, randomized, controlled trial in 170 adult patients with all five French-American-British (FAB) subtypes of MDS and with International Prognostic Scoring System scores of high risk, intermediate-2 and intermediate-1.
Eighty-nine patients were randomized to decitabine plus supportive care and 81 were randomized to supportive care. Patients randomized to the decitabine arm received the drug intravenously at a dose of 15 mg/m2 over a three-hour period every eight hours for three consecutive days. This treatment cycle was repeated every six 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.
Responses were classified using the MDS International Working Group criteria. Patients were required to be red blood cell and platelet transfusion independent during the period of response. The overall response rate (CR+PR) in the intent-to-treat population was 17 percent in the decitabine-treated group and 0 percent in the supportive care group (p<0.001).
In the decitabine-treated group the median duration of response was 288 days and the median time to response was 93 days. All but one of the decitabine-treated patients who responded did so by the fourth cycle. Decitabine treatment did not significantly delay the median time to acute myelogenous leukemia or death.
A total of 164 patients were accrued to two additional open-label, single-arm, multicenter studies of decitabine in patients with any of the FAB subtypes of MDS. The overall response rates in these two studies were 26 percent (N=66) and 24 percent (N=98).
The major toxicity of decitabine was myelosuppression as manifested by neutropenia, thrombocytopenia, anemia, and febrile neutropenia. Other common adverse events included nausea, vomiting, diarrhea, constipation, fever, edema, hyperglycemia, hypomagnesemia, hypokalemia, arthralgias, back pain, cough, headache, insomnia, rash, petechiae, and pallor.
No age- or gender- related differences in safety were detected. Patients with hepatic or renal dysfunction were not studied. Insufficient numbers of nonwhite patients were enrolled in these clinical trials to draw any conclusions.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.