Doxorubicin

Doxorubicin can be used both as monotherapy and in combination with other cytotoxic drugs in various doses, depending on the regimen of therapy. When individual dose should be guided by the data of special literature.

Intravenous administration

• as a monotherapy, the recommended dose per cycle is 60-75 mg / m² every three weeks. Usually the drug is administered once per cycle; however, the cyclic dose can be divided into several injections (for example, administered during the first three days in a row, or on the first and eighth day of the cycle). Cycles are repeated every 3-4 weeks.
• To reduce the toxic effect of doxorubicin, especially cardiotoxicity, a weekly regimen of 10-20 mg / m²;
• in combination with other anticancer drugs, doxorubicin is prescribed in a cyclic dose of 30-60 mg / m² every 3-4 weeks.

Liver dysfunction. In patients with hyperbilirubinemia, the dose of doxorubicin should be reduced in accordance with the concentration of total bilirubin:

• 50% when the concentration of bilirubin in the serum of 12-30 mg / l;
• 75% when the concentration of bilirubin in the serum is above 30 mg / l.

Other special patient groups. Prescribing lower doses or increasing the interval between cycles in patients who have previously received massive antitumor therapy is recommended. in children in elderly patients in obese patients (if body weight is more than 130% of the ideal, there is a decrease in systemic clearance of doxorubicin), as well as in patients with tumor infiltration of the bone marrow.

IV the introduction of doxorubicin should be carried out with caution. To reduce the risk of thrombosis and extravasation, it is recommended to inject doxorubicin through the system tube for intravenous administration, during the infusion of a 0.9% solution of sodium chloride or a 5% solution of dextrose, within 3-5 minutes. The total dose of doxorubicin should not exceed 550 mg / m². In patients who have previously received radiation therapy in the region of the lungs and mediastinum or were treated with other cardiotoxic drugs, the total dose of doxorubicin should not be more than 400 mg / m².

Before the introduction of the required dose of the drug should be dissolved in 0.9% sodium chloride solution or water for injection to a concentration of 2 mg / ml. The drug is administered IV struino slowly.

Introduction to the bladder

The recommended dose for intravesical administration is 30-50 mg per installation, with intervals between administrations from 1 week to 1 month, depending on the goals of therapy — treatment or prophylaxis. The recommended solution concentration is 1 mg / 1 ml of water for injection or 0.9% sodium chloride solution. After completion of the instillation, to ensure a uniform effect of the drug on the bladder mucosa, patients should roll over from side to side every fifteen minutes. As a rule, the drug should be in the bladder for 1-2 hours. At the end of the instillation, the patient should empty the bladder.

To prevent excessive dilution of the drug with urine, patients should be warned that they should refrain from taking fluid for 12 hours before instillation. Systemic absorption of doxorubicin during instillation into the bladder is very low.

When manifestations of local toxicity (chemical cystitis, which can manifest itself dysuria, polyuria, nykturiya, painful urination, hematuria, discomfort in the bladder, necrosis of the bladder wall) should be dissolved in 50-100 ml 0.9 % solution of sodium chloride. Particular attention should be paid to the problems associated with catheterization (for example, with obstruction of the urethra caused by massive intravesical tumors).

Intraarterial administration

Patients with hepatocellular carcinoma can be administered intraarterially to the main hepatic artery at a dose of 30-150 mg / m to provide intensive local exposure while reducing the overall toxic effect of doxorubicin.² with an interval of 3 weeks to 3 months. Higher doses should be used only in cases when in vitro removal of the drug is carried out simultaneously. Since this method is potentially dangerous, and when it is used, widespread tissue necrosis can occur, only doctors who are fluent in this technique can perform intraarterial administration.

Contraindicated in pregnancy and lactation (breastfeeding).

Doxorubicin treatment should be carried out under the supervision of physicians with experience in the use of anticancer drugs.

To reduce the risk of toxic damage to the heart, it is recommended that, during doxorubicin therapy, regular monitoring of its function, including evaluation of the left ventricular ejection fraction using echocardiography or multichannel radioisotope angiography, as well as ECG monitoring, is recommended. Early clinical diagnosis of heart failure due to the use of the drug is very important for its successful treatment. When signs of chronic cardiotoxicity are detected, doxorubicin treatment is immediately discontinued.

Acute cardiotoxicity in most cases is transient (reversible), and is usually not considered as an indication for discontinuation of doxorubicin therapy. Late (delayed) cardiotoxicity (cardiomyopathy) depends on the total dose. The probability of development of myocardial dysfunction is approximately 1-2% with a total dose of 300 mg / m²; the likelihood of this slowly increases with a total cumulative dose of 450-550 mg / m². Then the risk of developing congestive heart failure increases dramatically, so it is recommended not to exceed the total total dose of 550 mg / m². If the patient has any additional risk of cardiotoxicity (for example, a history of heart disease, prior anthracycline or anthracenedione therapy, prior radiotherapy of the mediastinum area, simultaneous use of other potentially cardiotoxic drugs such as cyclophosphamide and 5-fluorouracil) toxic effects may also occur at lower cumulative doses, and control of heart function must be especially strict. Cardiotoxicity caused by doxorubicin develops predominantly during the course of therapy or within two months after its termination, however, there may be delayed side effects (several months or even years after the end of therapy).

In the process of doxorubicin treatment, it is necessary to evaluate hematological parameters before and during each cycle of therapy, including determining the number of leukocytes, platelets, hemoglobin, blood corpuscles and liver function tests.

At the first signs of extravasation of doxorubition (burning or soreness at the injection site), the infusion should be stopped immediately and then resumed infused into another vein before the full dose is administered. Locally carry out measures to eliminate the effects of extravasation. It is advisable to use ice packs.

If possible, avoid introducing into the veins above the joints or into the veins of the extremities with impaired venous or lymphatic drainage.

When doxorubicin is used, hyperuricemia may be observed due to the rapid lysis of tumor cells, and therefore, patients are advised to determine the concentration of uric acid, potassium, calcium and creatinine during therapy. Activities such as increased hydration, alkalization of urine and prophylactic use of allopurinol to prevent hyperuricemia minimize the risk of complications associated with tumor lysis syndrome. In the treatment of hyperuricemia and gout, it may be necessary to adjust the doses of anti-gout agents as a result of an increase in the concentration of uric acid during treatment with the drug.

Patients with advanced neutropenia / leukopenia should be carefully monitored for signs of infection.

Refusal of immunization, if it is not approved by a doctor in the range of 3 months to 1 year after taking the drug; other family members of the patient living with him should not opt ​​for immunization with oral polio vaccine; avoid contact with people who have received a polio vaccine, or wear a protective mask covering the nose and mouth.

Men and women of childbearing age during doxorubicin treatment and for at least 3 months after should use reliable methods of contraception.

When working with doxorubicin, it is necessary to follow the rules for handling cytotoxic substances. The surface contaminated with the preparation is recommended to be treated with a dilute solution of sodium hypochlorite (containing 1% chlorine). In case of contact with the skin, immediately wash the skin with plenty of water with soap and water or sodium bicarbonate solution; in case of contact with eyes, delay the eyelids and rinse the eye (s) with plenty of water for at least 15 minutes.

Acute overdose of doxorubicin can lead to severe myelosuppression (mainly to leukopenia and thrombocytopenia), to toxic effects of the gastrointestinal tract, and cause acute heart damage.

The antidote to doxorubicin is not known. In case of overdose, symptomatic therapy is recommended.