Dakogen should be administered under the supervision of a doctor who has experience in the use of chemotherapy drugs.
The dacogen is administered by intravenous infusion. A central venous catheter is not required. Recommended 2 modes of dosing Dakogen: 5-day treatment OMJI and 3 or 5-day treatment for MDS. In both regimens, the recommended duration of treatment is at least 4 cycles, but more than 4 cycles may be required to achieve a response. In patients with OMJI the mean response time (complete response or complete response with incomplete platelet recovery) was 4.3 months. In patients with MDS with a 5-day dosing regimen, the average response was 3.5 cycles, and for 3 days - after 3 cycles. Treatment can continue as long as the response or stabilization of the disease persists, i.e. there is no obvious progression of the disease. If, after 4 cycles of treatment, the hematologic indices (platelet count and absolute neutrophil count) do not return to the baseline level, and also in case of progression of the disease (increase in the number of blast cells in the bone marrow or peripheral blood), the patient can be regarded as not responding to treatment, and Alternative therapy should be considered.
Premedication for the prevention of nausea and vomiting is usually not recommended, although it can be carried out if necessary.
Dosage regimen for AML
Dacogen is administered daily for 5 consecutive days at a dose of 20 mg / m2 surfaces
body by 1-hour intravenous infusion (ie, only 5 doses per treatment cycle). This cycle is repeated every 4 weeks, depending on the response to therapy and the manifestations of toxicity in the patient. The total daily dose should not exceed 20 mg / m2, and the total dose per cycle should not exceed 100 mg / m2. If you miss a regular dose, you should enter it as soon as possible. This treatment regimen can be performed on an outpatient basis.
Dosing regimen with MDS
Five-day dosing regimen
Dacogen is administered daily for 5 consecutive days at a dose of 20 mg / m2 body surface by 1-hour intravenous infusion (ie, only 5 doses per treatment cycle). This cycle is repeated every 4 weeks, depending on the response to therapy and the manifestations of toxicity in the patient. The total daily dose should not exceed 20 mg / m2, and the total dose per cycle should not exceed 100 mg / m2. If you miss a regular dose, you should enter it as soon as possible. This treatment regimen can be performed on an outpatient basis.
Three-day dosing regimen
Dacogen is used at a dose of 15 mg / m body surface by continuous 3-hour intravenous infusion every 8 hours for 3 days (ie, only 9 doses per treatment cycle). This cycle is repeated approximately every 6 weeks, depending on the response to therapy and the manifestations of toxicity in the patient. The total daily dose should not exceed 45 mg / m2, and the total dose per cycle is 135 mg / m2. If the next dose is missed, treatment should be resumed as soon as possible.
Treatment of myelosuppression and complications associated with it
Myelosuppression and undesirable phenomena associated with myelosuppression (thrombocytopenia, anemia, neutropenia and febrile neutropenia) are often found in previously treated and untreated patients with OMJI and MDS. Complications of myelosuppression include infection and bleeding. Treatment can be modified in patients who developed myelosuppression and the complications associated with it, described below:
With AML
Treatment can be delayed at the discretion of the attending physician if the patient experiences complications associated with myelosuppression described below:
- Febrile neutropenia (fever >38.5 ° C and the absolute number of neutrophils <1000 / μl)
- An active viral, bacterial or fungal infection (i.e., requiring intravenous anti-infective or intensive maintenance therapy)
- Bleeding (gastrointestinal, urogenital, pulmonary with a platelet count <25,000 / μl or in the central nervous system)
Treatment with Dakogen can be resumed after an improvement or stabilization of the condition with adequate treatment (anti-infective therapy, transfusion or the introduction of colony-stimulating factors).Decrease in the dose of Dacogen is not recommended.
With MDS
Five-day dosing regimen
It is not recommended to reduce the dose to optimize therapy. The dose should be adjusted as described below:
- Correction of dose in the first 3 cycles
In the first cycles of treatment, cytopenias of grade 3 and 4 are often observed, which may not be a sign of progression of MDS. Cytopenia, which existed before the start of treatment, can persist until the end of the third cycle of treatment.
During the first three cycles, in order to achieve the best possible benefit in conditions of moderate neutropenia (absolute neutrophil count <1000 / μl), every effort should be made to administer a complete dose of the preparation at standard intervals between cycles. Before the recovery of granulocyte counts above 500 / μL, concomitant antibiotic therapy can be performed in accordance with the clinical practice. At the same time, the doctor should also consider the need for early application of colony-stimulating factors for the prevention or treatment of infections in MDS patients.
Similarly, to achieve the best effect in conditions of moderate thrombocytopenia (platelet count <25,000 / μL),make every effort to introduce a full dose of the drug with standard intervals between cycles. In cases of bleeding, concomitant transfusion of platelet mass can be performed.
- Correction of dose after 3 cycles
The introduction of the next dose should be postponed with the development of the next toxicity, estimated at least as possibly related to the use of the drug:
- Severe complications of myelosuppression (infection and / or bleeding that do not stop with adequate therapy)
- Prolonged myelosuppression, defined as a hypocellular marrow (cells not more than 5% of the norm) without signs of progression for 6 or more weeks after the start of the treatment cycle.
If recovery is required (absolute neutrophil count> 1000 / μL, platelet count> 50,000 / μL), it takes more than 8 weeks, then treatment is stopped and within 7 days after the end of week 8 bone marrow is analyzed for detection progression of the disease. If the patient has received at least 6 cycles of treatment, and he has a favorable effect, then in the absence of progression, at the discretion of the doctor, a delay of the next cycle for more than 8 weeks is allowed.
Three-day dosing regimen
- Correction of dose in the first 3 cycles
In the first cycles of treatment, cytopenias of grade 3 and 4 are often observed, which may not be a sign of progression of MDS. Cytopenia, which existed before the beginning of treatment, may not be weakened until the end of the third cycle of treatment.
During the first three cycles, in order to achieve the best possible benefit in conditions of moderate neutropenia (absolute neutrophil count <1000 / μl), every effort should be made to administer a complete dose of the preparation at standard intervals between cycles. Before the recovery of granulocyte counts above 500 / μl, concomitant antibacterial prophylaxis can be carried out in accordance with the practice of the clinic. At the same time, the doctor should also consider the need for early application of colony-stimulating factors for the prevention or treatment of infections in MDS patients.
Similarly, to achieve the best effect in conditions of moderate thrombocytopenia (platelet count <25,000 / μL), every effort should be made to administer the complete dose of the drug at standard intervals between cycles. In cases of bleeding, concomitant transfusion of platelet mass can be performed.
- Correction of dose after the 3rd cycle
If the recovery of hematological parameters (absolute neutrophil count> 1000 / μL, platelet count> 50000 / μL) after the previous cycle of Dakogen administration takes more than 6 weeks, and the remaining cytopenia is regarded as associated with the use of the drug, the beginning of the next cycle is postponed and the dose is reduced by the following algorithm.
Any dose reduction is maintained until the end of treatment, i.e. back dose can not be increased.
- If the recovery takes more than 6 weeks, but less than 8 weeks, the beginning of the next cycle is postponed for up to 2 weeks, and the dose in the next cycle is reduced to
11 mg / m2 every 8 hours (33 mg / m2/ day, 99 mg / m2/cycle).
If the recovery takes more than 8 weeks, but less than 10 weeks, the start of the next cycle is delayed for a further 2 weeks, and the dose in the next cycle is reduced to 11 mg / m2 every 8 hours (33 mg / m2/ day, 99 mg / m2/cycle). In subsequent cycles, the dose is maintained depending on the clinical indications.
If the recovery takes more than 10 weeks, the drug is discontinued and the bone marrow is analyzed for 7 days after the end of the 10th week to determine the progression of the disease.If the patient has received at least 6 cycles of treatment, and he has a favorable effect, then in the absence of progression at the discretion of the doctor, a delay of the next cycle for more than 10 weeks is allowed.
Special patient groups:
Children: Safety and efficacy in children not established.
Liver failure: Studies in patients with hepatic insufficiency have not been conducted. Need for dose adjustment in patients with hepatic impairment
not evaluated. If the liver function worsens, patients should be carefully monitored (see sections "Special instructions" and "Pharmacological properties").
- Renal insufficiency: Studies in patients with renal insufficiency have not been carried out, however, according to clinical studies, patients with mild to moderate renal failure do not require dose adjustment. Clinical studies involving patients with severe renal failure have not been conducted.
Preparation and handling of the drug
The contents of the vial are for single use only.Avoid contact with the skin and use protective gloves. Standard procedures for handling antitumor drugs should be followed. Dacogen under aseptic conditions is dissolved in 10 ml of sterile water for injection. After dissolution, each 1 ml of the resulting solution contains about 5.0 mg of decitabine at a pH of 6.7-7.3.
Immediately after preparation, the preparation is diluted with infusion solutions (0.9% sodium chloride solution or 5% dextrose solution) to a final concentration of 0.1-1.0 mg / ml.
If the solution is not supposed to be injected within 15 minutes after preparation, the lyophilizate is dissolved in aseptic conditions in 10 ml of sterile water for injection and then diluted with a cold infusional solution (2-8 ° C) and stored at 2-8 ° C, no more than 4 hours.