FDA Approves 5-Day Dosing Regimen for Decitabine for Myelodysplastic Syndromes
By Yael Waknine
Medscape Medical News
March 15, 2010 — The US Food and Drug Administration (FDA) has approved a 5-day dosing regimen for decitabine (Dacogen, Eisai, Inc) for injection in the treatment of patients with myelodysplastic syndromes (MDS). Decitabine is the only hypomethylating agent approved for this dosing regimen.
MDS is a potentially life-threatening group of bone marrow diseases that alter the production of functional blood cells and can, over time, progress to acute myelogenous leukemia. Between 10,000 and 15,000 new cases are diagnosed in the United States each year.
The new decitabine outpatient dosing option offers a decreased infusion time — a 20-mg/m2 dose is administered as a continuous intravenous infusion over 1 hour for 5 days per cycle every 4 weeks compared with the previously approved regimen of 15 mg/m2 continuous intravenous infusion given over 3 hours for 3 days per cycle every 6 weeks.
FDA approval was based on data from 3 open-label, single-group, multicenter studies of patients with MDS with any of the French-American-British subtypes.
Results based on International Working Group 2000 criteria showed that patients achieved an overall response rate of 16% (complete remission, 15%; partial response, 1%). Median time to response was 162 days, with a median duration of 443 days.
Serious adverse events most commonly reported included neutropenia (37%), thrombocytopenia (24%), and anemia (22%).
The FDA advises that patients be treated for a minimum of 4 cycles; more cycles may be required for a complete or partial response. Liver chemistries and serum creatinine should be obtained before initiation of therapy; complete blood and platelet counts should be performed at least once before each dosing cycle to monitor response and toxicity.
Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not indicate MDS progression. In the presence of myelosuppression, subsequent decitabine treatment cycles should be delayed until recovery occurs (absolute neutrophil count ? 1000/μL; platelets ? 50,000/μL).
