Treatment Regimen in Myelodysplastic Syndromes (MDS): There are two regimens for DACOGEN administration. With either regimen, it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial response may take longer than 4 cycles.
Complete blood counts and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each cycle. Liver chemistries and serum creatinine should be obtained prior to initiation of treatment.
Treatment Regimen - Option 1: DACOGEN is administered at a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. This cycle should be repeated every 6 weeks. Patients may be premedicated with standard anti-emetic therapy.
If hematologic recovery (ANC ≥ 1,000/μL and platelets ≥ 50,000/μL) from a previous DACOGEN treatment cycle requires more than 6 weeks, then the next cycle of DACOGEN therapy should be delayed and dosing temporarily reduced by following this algorithm: Recovery requiring more than 6, but less than 8 weeks - DACOGEN dosing to be delayed for up to 2 weeks and the dose temporarily reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99 mg/m2/cycle) upon restarting therapy.
Recovery requiring more than 8, but less than 10 weeks - Patient should be assessed for disease progression (by bone marrow aspirates); in the absence of progression, the DACOGEN dose should be delayed up to 2 more weeks and the dose reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99 mg/m2/cycle) upon restarting therapy, then maintained or increased in subsequent cycles as clinically indicated.
Treatment Regimen - Option 2: DACOGEN is administered at a dose of 20 mg/m2 by continuous intravenous infusion over 1 hour repeated daily for 5 days. This cycle should be repeated every 4 weeks. Patients may be premedicated with standard anti-emetic therapy.
If myelosuppression is present, subsequent treatment cycles of DACOGEN should be delayed until there is hematologic recovery (ANC ≥ 1,000/μL platelets ≥ 50,000/μL ).
Patients with Non-hematologic Toxicity: Following the first cycle of DACOGEN treatment, if any of the following non-hematologic toxicities are present, DACOGEN treatment should not be restarted until the toxicity is resolved: serum creatinine ≥ 2 mg/dL; SGPT, total bilirubin ≥ 2 times ULN; and active or uncontrolled infection.
Treatment Regimen in Acute Myeloid Leukemia: In a treatment cycle, DACOGEN is administered at a dose of 20 mg/m2 body surface area by intravenous infusion over 1 hour repeated daily for 5 consecutive days (i.e., a total of 5 doses per treatment cycle). The total daily dose must not exceed 20 mg/m2 and the total dose per treatment cycle must not exceed 100 mg/m2. If a dose is missed, treatment should be resumed as soon as possible. The cycle should be repeated every 4 weeks depending on the patient's clinical response and observed toxicity. It is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial remission may take longer than 4 cycles to be obtained. Treatment may be continued as long as the patient shows response, continues to benefit or exhibits stable disease, i.e., in the absence of overt progression.
If after 4 cycles, the patient's hematological values (e.g., platelet count or absolute neutrophil count), have not returned to pre-treatment levels or if disease progression occurs (peripheral blast counts are increasing or bone marrow blast counts are worsening), the patient may be considered to be a non-responder and alternative therapeutic options to DACOGEN should be considered.
Pre-medication for the prevention of nausea and vomiting is not routinely recommended but may be administered if required.
Management of Myelosuppression and Associated Complications In AML: Myelosuppression and adverse events related to myelosuppression (thrombocytopenia, anemia, neutropenia, and febrile neutropenia) are common in both treated and untreated patients with AML. Complications of myelosuppression include infections and bleeding. Treatment may be delayed at the discretion of the treating physician, if the patient experiences myelosuppression-associated complications, such as those described as follows: Febrile neutropenia (temperature ≥ 38.5ºC and absolute neutrophil count < 1,000/μL).
Active viral, bacterial or fungal infection (i.e., requiring intravenous anti-infectives or extensive supportive care).
Hemorrhage (gastrointestinal, genito-urinary, pulmonary with platelets < 25,000/μL or any central nervous system hemorrhage).
Treatment with DACOGEN may be resumed once these conditions have improved or have been stabilized with adequate treatment (anti-infective therapy, transfusions, or growth factors).
In clinical studies, approximately one-third of patients receiving DACOGEN required a dose-delay. Dose reduction is not recommended.
Special Populations: Pediatrics: The safety and effectiveness in pediatric patients have not been established.
Hepatic impairment: Studies in patients with hepatic impairment have not been conducted. The need for dosage adjustment in patients with hepatic impairment has not been evaluated. If worsening hepatic function occurs, patients should be carefully monitored (see Precautions, Pharmacology: Pharmacokinetics under Actions).
Renal impairment: Studies in patients with renal impairment have not been conducted; however, data from clinical trials that included patients with mild-moderate impairment indicated no need for dosage adjustment. Patients with severe renal impairment were excluded from these trials (see Pharmacology: Pharmacokinetics under Actions).
Administration: DACOGEN is administered by intravenous infusion. A central venous catheter is not required. For instructions on reconstitution and dilution of the medicinal product before administration, see Instructions for Use and Handling and Disposal under Cautions for Usage.