Doxorubicin (other names: Adriamycin, Rubex) is a chemotherapy drug from the group of anthracycline antibiotics. Along with it, this group includes: Epirubicin, Idarubicin, Daunorubicin. It is obtained from bacteria of the genus Streptomycetes, namely Streptomyces peuceticus var. caesius. Doxorubicin is used to treat various cancers. The drug solution is a red liquid. This drug and its side effects are familiar to women who have undergone red chemotherapy for breast cancer.
- How does Doxorubicin destroy tumor cells?
- What types of cancer can this drug be used for?
- Course of treatment with Doxorubicin
- Possible side effects
- Rare dangerous side effects
- Why is Doxorubicin a “red” chemotherapy?
- How is the patient's condition monitored during treatment?
- Pregnancy and Fertility
How does Doxorubicin destroy tumor cells?
All chemotherapy drugs destroy cancer cells or suppress their proliferation, but they do this in different ways. Doxorubicin is an antitumor antibiotic with antiproliferative and antimitotic effects. Its antitumor effects are associated with the following mechanisms:
- The drug penetrates the DNA molecule, blocks its replication and protein synthesis.
- Doxorubicin inhibits the enzyme DNA topoisomerase II, which affects the spatial structure of DNA and plays an important role in the process of cell growth and division.
- Chemotherapy molecules are capable of oxidizing to form free radicals that damage the cancer cell.
All these effects apply not only to tumor cells, but also to healthy cells. Doxorubicin can cause serious side effects. We will talk about them below.
Pharmacological properties of the drug Doxorubicin
Antitumor anthracycline antibiotic obtained from Streptomyces peucetius var. caesius . The mechanism of action is due to the ability to interact with DNA and interfere with the synthesis of nucleic acids. Reduces mitotic activity and causes chromosomal aberrations. Has a pronounced immunosuppressive effect. Highly active against many forms of tumors. It has immunosuppressive activity, cardiotoxicity, and inhibits hematopoiesis. Ineffective when taken orally. After intravenous administration, the concentration of doxorubicin in the blood plasma decreases rapidly, which is likely due to its distribution in the tissues of the body. Doxorubicin does not penetrate the BBB and is excreted mainly in bile and feces (within 7 days - 40–50% of the administered dose). About 5% of the administered dose is excreted in the urine within 5 days. If liver function is impaired, the removal of doxorubicin from the body slows down, resulting in its accumulation in the blood plasma and tissues.
What types of cancer can this drug be used for?
Doxorubicin is used for cancer of the breast, stomach, uterus, head and neck, kidney, liver, ovaries, and thyroid gland. It is also used to treat acute lymphoblastic and myeloblastic leukemia, bone sarcomas, Hodgkin and non-Hodgkin lymphomas, multiple myeloma, neuroblastoma, and soft tissue sarcoma.
Doxorubicin is usually prescribed in combination with other chemotherapy drugs that have different mechanisms of action. This increases the effectiveness of treatment.
Course of treatment with Doxorubicin
Doxorubicin is administered intravenously in different ways:
- Through an IV.
- Using an infusion pump - for a long time at a certain speed.
- Through a central venous catheter installed, for example, in the subclavian vein.
- Through an infusion venous port system: a small reservoir is sutured under the skin, connected by a catheter to the subclavian vein. One of the walls of the reservoir is a membrane, it is located directly under the skin. The drug is injected into the reservoir by piercing the skin and membrane with a special needle. Typically, a patient is implanted with a port system when drugs need to be administered over a long period of time.
- Sometimes, for bladder cancer, Doxorubicin is injected directly into the bladder through a catheter.
The drug is not available in tablets and is not used.
IMPORTANT. Doxorubicin is a vesicant and has a strong blister effect. If you inject it into the subcutaneous fatty tissue, it will cause necrosis - tissue death. This is a serious complication; after unsuccessful administration of the drug, skin grafting may be required. Therefore, the procedure must be performed by specially trained medical workers, in compliance with all rules. If redness appears on the skin during administration, you should immediately inform your doctor or nurse.
Therapy can be carried out both in a hospital and on an outpatient basis. The dosage of Doxorubicin depends on the type of cancer, the patient’s weight and height, his state of health, and concomitant diseases. Treatment, as with other chemotherapy drugs, is carried out in cycles. After the administration of Doxorubicin, there should be a “respite” for several days - this is necessary so that the body can recover and no serious side effects arise. Then the cycle is repeated. The course may consist of several cycles and last several months.
Drug interactions Doxorubicin
Bleomycin, vinblastine, vincristine, thiophosphamide, methotrexate, etoposide, prednisolone, fluorouracil and cisplatin are compatible with doxorubicin. Doxorubicin should not be administered in the same syringe with heparin and fluorouracil. It is incompatible with aminophylline, cephalothin sodium salt, dexamethasone and hydrocortisone. Prescribing doxorubicin concomitantly with cyclophosphamide, mitomycin, or mediastinal radiotherapy increases the risk of cardiotoxicity.
List of pharmacies where you can buy Doxorubicin:
- Moscow
- Saint Petersburg
Possible side effects
Like any chemotherapy drugs, Doxorubicin damages DNA not only in tumor cells, but also in other actively reproducing cells. Because of this, it may cause some side effects.
But do not be alarmed if your doctor has prescribed this drug to you. Firstly, you will not immediately experience the entire list of side effects that we list below. Secondly, most of them are quite predictable in terms of time of onset, severity and duration. After completion of treatment, they gradually disappear. Thirdly, the side effects of Doxorubicin can be kept under control, and Euroonko has everything necessary for this.
Common side effects include: nausea and vomiting (beginning to occur approximately 2 weeks after starting treatment), pain at the injection site, hair loss, anemia and an increased risk of infection. More than a third of patients experience these symptoms. 10–30% of patients experience symptoms such as mouth ulcers, watery eyes, darkening of the skin at the site of radiation therapy, and red urine. Infertility occurs in 10% of cases in men and women.
Decreased immunity. When using Doxorubicin, the level of leukocytes in the blood decreases and the risk of infection increases. You should immediately inform your doctor about symptoms such as fever over 37.5 °C, sore throat, cough, loose stools, and frequent urination.
Increased bleeding. Occurs due to a decrease in platelet levels. It manifests itself in the form of hematomas (bruises) on the skin, bleeding gums, and nosebleeds. Some patients may require platelet transfusions.
Anemia. Chemotherapy with Doxorubicin can lead to a decrease in the level of red blood cells in the blood. There is pallor, a constant feeling of fatigue, headaches and dizziness, shortness of breath. Some patients require red blood cell transfusions.
Increased fatigue. This symptom worsens toward the end of chemotherapy and persists for several weeks after completion. At this time, you need to try to relax more and be in the fresh air.
Changes in the oral mucosa. The oral mucosa may become sensitive and painful, and sometimes ulcers appear on it. Increased risk of infection. In order to cope with these symptoms during treatment with Doxorubicin, you need to follow some recommendations:
- Use a soft toothbrush.
- Drink more fluids.
- Avoid eating foods that irritate the mucous membranes of your mouth.
- Stop drinking alcohol and smoking.
Decreased appetite. This is a common side effect of Doxorubicin and other chemotherapy drugs. If you eat very little for several days due to lack of appetite, consult your doctor.
Pink-red coloration of urine. Urine may change color within 48 hours after using the drug. There's nothing wrong with that. This is not blood, this symptom occurs because the Doxorubicin solution is red.
Diarrhea. If the stool becomes liquid, you should immediately consult a doctor. This symptom may be due to the drug affecting the intestines or an infection.
Hair loss. Hair may become thin or fall out completely, and not only on the head: many patients lose eyebrows and eyelashes. Most often this occurs after the first or second course of treatment with Doxorubicin. For many patients, this side effect seems the most terrible, but in fact there is no reason to panic. Typically, hair grows back soon after chemotherapy is completed. In order to protect them, special cooling caps are used during procedures.
Changes in skin and nails. Nails may become brittle, skin may become dry, become more sensitive to the sun, and dark spots may appear. Usually these symptoms are temporary.
Other side effects are possible, but these can usually be managed successfully. Doctor's recommendations and modern methods of supportive treatment help patients comfortably tolerate Doxorubicin chemotherapy.
Doxorubicin (Doxophyllinum)
DOXORUBICIN should only be used under the supervision of a physician experienced in the use of anticancer drugs.
To reduce the risk of severe toxic cardiac damage, regular monitoring of cardiac function is recommended before and during doxorubicin therapy, including assessment of left ventricular ejection fraction using echocardiography or multichannel radioisotope angiography, as well as ECG monitoring. Early clinical diagnosis of drug-induced heart failure is very important for its successful treatment. If signs of chronic cardiotoxicity are detected, treatment with doxorubicin is stopped immediately.
Acute cardiotoxicity in most cases is transient (reversible) in nature, and is usually not considered an indication for discontinuation of doxorubicin therapy. Late (delayed) cardiotoxicity (cardiomyopathy) depends on the total dose. The probability of developing myocardial dysfunction is approximately 1-2% with a total dose of 300 mg/m2; then slowly increases with a total total dose of 450-550 mg/m2. With a further increase in dose, the risk of developing congestive heart failure increases quite sharply, so it is recommended not to exceed the total total dose of 550 mg/m2.
Monitoring of cardiac function should be particularly stringent in patients receiving high cumulative doses of the drug and in patients with risk factors for increased cardiotoxicity (eg, overt or underlying cardiovascular disease, prior or concomitant radiation therapy to the mediastinal/pericardial region, prior therapy with other anthracyclines or anthracenediones and concomitant therapy with drugs that reduce cardiac contractility). Cardiotoxicity may also develop when lower cumulative doses of doxorubicin are used, regardless of the presence of risk factors. Children and adolescents are at increased risk of developing late cardiotoxicity from doxorubicin. This risk may be higher in women than in men.
The toxicity of doxorubicin and other anthracyclines or anthracenediones is likely to be additive.
Like other cytotoxic agents, doxorubicin can cause myelosuppression. A complete blood count, including white blood cell count and platelet count, should be performed before and during each cycle of doxorubicin therapy.
In patients receiving anthracyclines, including doxorubicin, cases of the development of secondary leukemia with or without a preleukemic phase have been described. Secondary leukemia is more common when these drugs are used in combination with other antineoplastic agents that cause DNA damage, radiation therapy, and in patients who have previously received intensive cytotoxic therapy or high-dose anthracyclines. Secondary leukemias can have a latent period lasting 1-3 years.
Mucositis/stomatitis usually develops soon after administration of the drug and in severe cases can lead to ulceration of the mucous membrane within a few days. In most cases, these adverse events resolve by the third week of therapy.
Before and during drug therapy in patients, it is necessary to monitor liver function indicators (the level of total bilirubin in the blood serum). In patients with elevated bilirubin levels, drug clearance may be slowed and overall toxicity may increase. At the first sign of extravasation of doxorubicin (burning or soreness at the injection site), the infusion should be stopped immediately and then the infusion should be resumed in another vein until the full dose is administered; carry out local measures to eliminate the consequences of extravasation. It is advisable to use ice packs.
When using the drug intravesically, special attention should be paid to conditions that create obstacles to catheterization (for example, urethral obstruction caused by massive bladder tumors).
When using doxorubicin, hyperuricemia may occur due to rapid lysis of tumor cells, and therefore patients are advised to determine the level of uric acid, potassium, calcium and creatinine in the blood during therapy. Interventions such as hydration, alkalization, and prophylaxis with allopurinol to prevent hyperuricemia can minimize the risk of complications associated with tumor lysis syndrome.
In men, doxorubicin is mutagenic and can cause damage to sperm chromosomes. Men and women of childbearing potential should use reliable methods of contraception during treatment with doxorubicin and for at least 3 months thereafter.
When working with the drug, you must follow the rules for handling cytotoxic substances.
Unused drug residues and all instruments and materials used in the preparation of infusion solutions and drug administration, including gloves, must be destroyed according to an approved cytotoxic waste disposal procedure. It is recommended to treat the surface contaminated with the drug with a diluted solution of sodium hypochlorite (containing 1% chlorine). If the drug gets on the skin, immediately wash the skin thoroughly with soap and water or sodium bicarbonate solution; If it gets into your eyes, pull back your eyelids and rinse your eye(s) with plenty of water for at least 15 minutes.
Rare dangerous side effects
An extremely rare but very serious side effect of Doxorubicin is a decrease in the pumping function of the heart. The risks are increased in elderly patients, people receiving radiation therapy to the chest area, and taking other drugs with cardiotoxic effects. Heart problems may occur several years after treatment has been completed. Before starting a course of chemotherapy, the doctor must prescribe an ultrasound and other tests and monitor the patient’s heart condition during the treatment process.
Sometimes tumor decay syndrome occurs - a condition when, under the influence of the drug, many tumor cells die, and the products of their destruction enter the blood. Symptoms appear within 24–48 hours after administration of the drug, and kidney failure may occur. To prevent this complication, infusion therapy is prescribed.
Another extremely rare complication is leukemia. It may occur several years after treatment.
Why is Doxorubicin a “red” chemotherapy?
Colonies of microorganisms Streptomyces peucetius, which produce anthracyclines, have a characteristic red color. The medicine in the bottle is of a similar color. That's why women undergoing treatment for breast cancer call this chemotherapy "red."
“Red” chemotherapy is feared because it causes more severe side effects than “white,” “yellow,” and “blue” drugs. But there is no reason to be afraid: before prescribing a medicine, the doctor will thoroughly assess the patient’s health, weigh the pros and cons, prescribe supportive therapy and will constantly monitor the condition during the treatment process. Euroonko patients tolerate any chemotherapy comfortably - this is one of the most important principles of our work.
How is the patient's condition monitored during treatment?
Before prescribing Doxorubicin, general and biochemical blood tests are performed, the condition of the kidneys, liver, and heart is assessed. The tests are repeated during and after the course of chemotherapy. If you are bothered by any symptoms, you should immediately tell your doctor about them.
Sometimes Doxorubicin has to be stopped due to side effects, in which case the doctor will select another drug. At Euroonco, you can create a “molecular portrait” of a tumor and select the optimal combination of chemotherapy drugs, prescribing personalized chemotherapy that will be most effective for a particular patient.
Due to the pronounced side effects, many patients perceive Doxorubicin as a “powerful” chemotherapy drug. But resistance to it sometimes develops—the tumor becomes resistant and no longer responds to treatment. In such cases, other drugs are prescribed.
Pregnancy and Fertility
The drug is dangerous for the fetus, therefore it is impossible for a woman to become pregnant during treatment with Doxorubicin and for at least 6 months before and after completion of the course. You can have sex during chemotherapy, but you must use effective contraception. The drug passes into breast milk, so breastfeeding is also contraindicated.
After using Doxorubicin, problems with conceiving a child may occur. 10% of patients develop infertility. Therefore, if the patient plans to have children in the future, this issue should be discussed with the doctor in advance. A chemotherapy doctor may recommend sperm cryopreservation for a man and egg cryopreservation for a woman.
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Special instructions for the use of Doxorubicin
Strict hematological and cardiac monitoring is necessary, peripheral blood composition and ECG studies should be performed before starting therapy and before each subsequent course. Doxorubicin is widely used in complex polychemotherapy regimens, but it should not be prescribed earlier than 1 month after completion of the previous cycle of chemotherapy using other antitumor agents. The antitumor activity of doxorubicin is approximately the same regardless of the administration schedule - whether it is administered as a bolus (total dose) once a month, weekly or by gradual continuous administration, however, different administration regimens differ significantly in the severity of adverse reactions. In particular, with prolonged administration, in contrast to bolus administration, nausea and vomiting are significantly less pronounced.
