Adverse events (AEs) were consistent with the known decitabine safety profile and without major differences between the treatment arms. The most commonly reported Grade 3 or 4 adverse events were thrombocytopenia (reported in 40%, 32%, and 35% and 14% of subjects in the Dacogen, treatment choice, cytarabine and supportive care groups, respectively), anemia (34%, 25%, 27% and 14% respectively), neutropenia (32%, 42%, 20% and 3% respectively) and febrile neutropenia (32%, 22%, 25% and 0% respectively).About Acute Myeloid Leukemia Acute myeloid leukemia (AML) is an aggressive, fast-growing cancer that starts inside the bone marrow with production of abnormal blood cells. It is generally a disease of older adults, with an average patient age of 64 at diagnosis, and is slightly more common among men than women. The most common symptoms of AML include tiredness, shortness of breath, bruising or bleeding easily, fever and infections. When diagnosed, treatment is to be started with minimal delay as AML usually results in death within just a few months if left untreated. AML can sometimes spread to other parts of the body including the lymph nodes, liver and spleen. In older adults, induction chemotherapy leads to a high 30-day mortality, and most patients are not candidates for or are unwilling to undergo this aggressive therapy. Therefore, treatment options are limited and overall, irrespective of therapy, median survival is merely 2.4 months. About DACOGEN (decitabine) DACOGEN is a DNA hypomethylating agent currently approved for the treatment of myelodysplastic syndromes (MDS) in more than 30 countries worldwide including key markets such as the United States, Brazil, China, India, Russia and Turkey. Eisai Inc. manages the product rights in the United States, Canada and Mexico and Janssen-Cilag International NV and other affiliates of Cilag GmbH International manage the marketing and development rights for DACOGEN in all other markets.
Dacogen is approved in selected markets 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, chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups.Important Safety Information Treatment with DACOGEN is associated with neutropenia and thrombocytopenia. Complete blood and platelet counts should be performed as needed to monitor response and toxicity but at a minimum prior to each dosing cycle. After administration of the recommended dosage for the first cycle, treatment for subsequent cycles should be adjusted if indicated by dose adjustment guidelines. Clinicians should consider the need for early institution of growth factors and/or antimicrobial agents for the prevention or treatment of infections in patients with MDS. DACOGEN may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with DACOGEN and for 1 month following completion of treatment. Women of childbearing potential should be counseled to use effective contraception during this time. Men should be advised not to father a child while receiving treatment with DACOGEN and for 2 months following completion of treatment. DACOGEN may cause fetal harm. Men with female partners of childbearing potential should use effective contraception during this time. In the phase 3 clinical trial, the highest incidence of Grade 3 or Grade 4 adverse events in the DACOGEN arm was neutropenia (87%), thrombocytopenia (85%), febrile neutropenia (23%), and leukopenia (22%). Bone marrow suppression was the most frequent cause of dose reduction, delay, and discontinuation. Six patients had fatal events associated with their underlying disease and myelosuppression (anemia, neutropenia, and thrombocytopenia) that were considered at least possibly related to drug treatment. Of the 83 DACOGEN-treated patients, 8 permanently discontinued therapy for adverse events compared to 1 of 81 patients in the supportive care arm.
In the single-arm study, the highest incidence of Grade 3 or Grade 4 adverse events was neutropenia (37%), thrombocytopenia (24%), and anemia (22%). Seventy-eight percent of patients had dose delays, the median duration of this delay was 7 days. Hematologic toxicities and infections were the most frequent causes of dose delays and discontinuation. Eight patients had fatal events due to infection and/or bleeding that were considered at least possibly related to drug treatment. Nineteen of 99 patients permanently discontinued therapy for adverse events.Other commonly occurring reactions include fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia. If hematologic recovery from a previous DACOGEN treatment cycle requires more than 6 weeks when administering the 3-day dosing, then the next DACOGEN cycle should be delayed and dosing temporarily reduced. When administering the 5-day dosing, the DACOGEN cycle should be delayed until there is hematologic recovery. If the following nonhematologic toxicities are present, DACOGEN treatment should not be restarted until the toxicity is resolved: (1) serum creatinine ≥2 mg/dL; (2) SGPt, total bilirubin ≥2 × ULN; and (3) active or uncontrolled infection. Because there are no data on use of DACOGEN in patients with renal or hepatic dysfunction, DACOGEN should be used with caution in these patients. For DACOGEN full prescribing information, please click here. About SuperGen SuperGen is a pharmaceutical company dedicated to the discovery and development of novel cancer therapeutics in epigenetic and cell signaling modulation. The Company develops products through biochemical and clinical proof of concept to partner for further development and commercialization. SuperGen developed Dacogen and receives significant royalties on global sales. On April 6, 2011, SuperGen entered into a definitive merger agreement to acquire Astex Therapeutics Limited, a UK based biotechnology company. The transaction is subject to customary regulatory, legal and shareholder approvals. For more information about SuperGen, please visit http://www.supergen.com.