Treatment of advanced prostate cancer, especially in patients with hormone-refractory tumors and in initial treatment in patients with prostate cancer, who have predictive factors that indicate the possibility of an inadequate response to hormonal treatment.
Composition:
1 vial contains 300 mg estramustine phosphate.
Action:
An anti-cancer drug with a dual mechanism of action. Estron and estradiol, estramustine phosphate metabolites, show anti-gonadotropic activity, as a result of which the amount of testosterone decreases. Estramustine is converted to estromustine; both metabolites show anti-mitotic effects on tumor cells by inhibiting the formation of microtubules in metaphase and disintegration of microtubules in interphase. Estramustine regulates the activity of P-glycoprotein in resistant cell lines, which increases the intracellular accumulation of the product and enhances the cytotoxic effect of the simultaneously used cytotoxic drugs. Estramustine phosphate is a prodrug, it binds to proteins in 99%. After intravenous administration, undistributed estramustine phosphate is detected in the plasma but undergoes rapid changes. T0,5 is 1.2 hours. Estramustine is metabolised to estromustine and then to the corresponding estrogens: estradiol and estrone. Estramustine and estromustine are secreted along with bile and faeces. Estradiol and estriol are subject to further metabolism and partial elimination in the urine.
Contraindications:
Hypersensitivity to the components of the preparation, nitrogen mustard or estradiol. Severe cardiovascular disease: ischemic heart disease, active thromboembolism or complications associated with fluid retention. Severe liver disease.
Precautions:
Caution should be used in patients with a history of thrombophlebitis, thrombotic or thromboembolic disorders, especially if they have occurred in connection with estrogen therapy and in patients with cerebrovascular disease or ischemic heart disease. In the case of long-term treatment, it is recommended to check the number of blood cells and the liver and kidneys. Patients with impaired circulation and heart failure should be closely monitored. It is also recommended to check proper diuresis and blood pressure. Due to the possibility of reduced Glucose tolerance, caution should be exercised when administering the drug to patients with diabetes. Caution should be exercised in the case of diseases that may be adversely affected by fluid retention, e.g. epilepsy, migraine, and renal failure. Due to the effect of the drug on Calcium and phosphorus metabolism, caution should be exercised in patients with metabolic bone diseases with associated hypercalcemia or patients with renal insufficiency. As the drug may be more slowly metabolised in patients with impaired hepatic function, it should be used with caution in these patients. In the event of extravasation, stop the injection or infusion immediately. Ice or local anesthetics may be used to relieve pain. If necessary, topical corticosteroids and close observation of the patient are recommended. Patients taking the drug should not be vaccinated with live vaccines because it can lead to serious infections. Response to dead or inactivated vaccines may be impaired.
Pregnancy and lactation:
The drug is not intended for women. Both estradiol and nitrogen mustard have mutagenic properties; therefore, up to 6 months after the end of therapy, effective contraception should be used.
Side effects:
Rare: anemia, leukopenia, thrombocytopenia; hypersensitivity reactions; confusion, depression; headache, drowsiness; diarrhea; allergic rash, angioneurotic edema (Quinckie edema, laryngeal edema); muscular weakness. Uncommon: vomiting, especially during the first two weeks of treatment; liver dysfunction.Common: congestive heart failure, ischemic heart disease, myocardial infarction; thromboembolism, hypertension, fluid retention; nausea; gynecomastia, impotence; thrombophlebitis at the injection site.
Dosage:
Intravenously. Initial treatment: 5 mg / kg m.g. (300-450 mg) / day, administered for 3 weeks. Maintenance treatment: 300 mg of the drug twice a week or a medicine in the form of capsules administered according to the recommended dosage. The drug should be administered in a very slow intravenous injection (3-5 min.) By a needle placed in the peripheral vein or by central venous access. During treatment, the patient should be kept in a lying position. When infused, the drug should be dissolved in 250 ml of 5% glucose solution (pH 5.5 ± 0.5, caution should be used in patients with diabetes). The duration of infusion should not exceed 3 hours. If no improvement occurs after 3-4 weeks of treatment, treatment should be discontinued.
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