doxorubicin

Doxorubicin - also known as adriamycin - is an anthracycline antibiotic with an antineoplastic action that has a broad antitumor spectrum.

Doxorubicin - Chemical Structure

Indications

For what it uses

The use of doxorubicin is indicated for the treatment of the following diseases:

Breast cancer;
Osteosarcoma;
Small cell lung cancer;
Bladder cancer;
Hodgkin's and non-Hodgkin's lymphoma;
Acute lymphatic leukemia;
Acute myeloblastic leukemia;
Multiple myeloma;
Advanced endometrial cancer;
Thyroid tumors;
Some types of metastatic and non-bladder tumors;
Wilms tumor (a type of pediatric tumor);
Advanced neuroblastoma (a pediatric tumor affecting nerve tissue).

Warnings

Doxorubicin should only be administered by specialized personnel and only under the strict supervision of a doctor who specializes in the administration of anticancer drugs.

Great caution should be used when administering doxorubicin in the following cases:

In elderly patients;
In patients who have suffered from heart disease;
In patients who have suffered bone marrow damage;
In patients treated with radiotherapy at the level of the thoracic cavity (mediastinum);
In patients treated with other anthracycline anticancer agents.

Vaccinations are not recommended during doxorubicin therapy.

Since doxorubicin induces myelosuppression (bone marrow suppression), blood counts should be checked before each new drug is given.

During the whole period of treatment with doxorubicin it is necessary to carry out regular checks of the chest to verify the pulmonary function.

Since doxorubicin can cause cardiomyopathies, regular electrocardiograms must be performed.

Since doxorubicin can cause hyperuricemia (increased levels of uric acid in the blood), uricemia must be kept under strict control.

Continuous monitoring of liver and kidney function is necessary during treatment with doxorubicin.

Doxorubicin cannot be administered intravenously in the following cases:

In patients with myelosuppression;
In patients with stomatitis;
In patients suffering from infectious diseases;
In patients whose liver function is severely impaired;
In patients with heart disease;
In patients previously treated with maximum doses of other anthracycline anticancer drugs.

Intravesical doxorubicin, on the other hand, cannot be administered in the following cases:

In patients whose cancer has spread to the bladder walls;
In patients with bladder inflammation;
In patients with urinary infections;
In patients with hematuria (blood in the urine);
In patients who have problems with the use of the catheter.

Doxorubicin can cause side effects that can compromise vehicle driving or the use of machinery.

Interactions

Caution should be used in the administration of doxorubicin in patients who have taken other drugs capable of altering heart function. These drugs include 5-fluorouracil, cyclophosphamide, paclitaxel, trastuzumab (anticancer drugs) and calcium channel blockers (drugs used to treat hypertension).

The administration of doxorubicin in patients previously treated with 6-mercaptopurine (another anticancer medicine) causes an increased risk of adverse effects on the liver.

Side effects of doxorubicin-induced bone marrow may increase in patients who have been treated with the following drugs:

Cytarabine, cisplatin or cyclophosphamide, other anticancer drugs;
sulfa drugs, antibacterial drugs;
Chloramphenicol, an antibiotic;
Phenytoin, an antiepileptic;
Amidopirin derivatives, an NSAID;
Antiretroviral drugs for the treatment of HIV.

Furthermore, cyclophosphamide can increase the bladder side effects induced by doxorubicin.

Concomitant intake of doxorubicin and ciclosporin (an immunosuppressive drug used in the prevention of rejection in transplants) or cimetidine (a drug used in the treatment of gastric ulcer) can cause an increase in the plasma concentration of doxorubicin itself.

Concomitant intake of doxorubicin and phenobarbital (used in the treatment of epilepsy) or rifampicin (an antibiotic) may cause a reduction in the plasma concentration of doxorubicin and - consequently - a reduction in its therapeutic efficacy.

Doxorubicin may decrease the effectiveness of digoxin (a drug used to increase the strength of cardiac contraction).

Taking doxorubicin concomitantly with radiation therapy may cause an increase in side effects.

Side effects

Doxorubicin can induce various types of side effects. The type of adverse effects and the intensity with which they occur vary from individual to individual.

Below are the main side effects that may occur following treatment with doxorubicin.

Allergic reactions

Doxorubicin can trigger allergic reactions in sensitive individuals. These reactions can manifest with swelling of the lips, face and neck resulting in difficulty breathing, hives, rashes and anaphylactic shock.

Myelosuppression

Treatment with doxorubicin can cause severe myelosuppression. This suppression leads to a reduction in the production of blood cells (reduced hematopoiesis) which can lead to:

Anemia (decrease in hemoglobin blood levels), the main symptom of the onset of anemia is the feeling of physical exhaustion;
Leukopenia (decreased white blood cell levels), with increased susceptibility to contraction of infections;
Plateletopenia (decrease in the number of platelets), this leads to the appearance of bruising and abnormal bleeding with an increased risk of bleeding.

Furthermore, bone marrow suppression can cause blood poisoning, septic shock, tissue hypoxia and tissue death. In any case, this side effect is usually temporary.

Gastrointestinal disorders

Treatment with doxorubicin may cause nausea, vomiting, abdominal pain and diarrhea.

Vomiting can be controlled by anti-emetic drugs, while diarrhea can be treated with anti-diarrheal drugs. If, however, these symptoms persist or occur in severe form, the oncologist should be informed that he will decide how to proceed. In any case, it is good to drink a lot to replenish lost fluids.

In addition, the drug can cause bleeding from the stomach or intestines, ulcers and necrosis of tissue cells in the large intestine with bleeding and infections. These adverse effects may occur especially when doxorubicin is given in combination with cytarabine (another anticancer medicine).

Kidney and urinary tract disorders

Treatment with doxorubicin can cause acute renal failure, urination difficulties, pain or burning when urinating, reduced urine output, increased urination frequency, bladder cramps and bladder inflammation with blood in the urine.

When doxorubicin is administered intravesically it can cause chemical cystitis.

Furthermore, the drug causes the urine to turn red.

Cardiac disorders

Treatment with doxorubicin can cause cardiotoxicity, heart rhythm disorders, reduction in the amount of blood pumped from the heart to the body, left heart failure, pericarditis, atrioventricular or bundle branch block and cardiomyopathy with fatal outcomes.

Cardiotoxicity may be increased in patients who have previously been treated with radiotherapy or other cardiotoxic drugs, in elderly patients or in hypertensive patients.

Leukemia

When doxorubicin is associated with other anticancer drugs, it can promote the onset of leukemia.

Hand-foot syndrome

Doxorubicin can cause this syndrome which is characterized by redness, pain, swelling and tingling in the palm of the hands and / or the soles of the feet. Sometimes, blisters may also form.

Skin and subcutaneous tissue disorders

Treatment with doxorubicin can cause hair loss, photosensitivity reactions, redness of the skin, itching, rash, hives, pigmentation of the skin and nails, nail detachment and actinic keratosis.

Liver disorders

Treatment with doxorubicin can cause temporary changes in the blood levels of liver enzymes, but it can also cause severe liver damage leading to the development of liver cirrhosis.

Infertility

Treatment with doxorubicin may cause amenorrhea (ie lack of menstrual cycle) in women and azoospermia or oligospermia (respectively, sperm count or sperm reduction) in men.

Other side effects

Other side effects that may occur following treatment with doxorubicin are:

Allergic reactions in parts of the body already treated with radiotherapy;
Temperature;
Tremors;
dizziness;
Hyperuricemia;
Mucositis;
Esophagitis;
Stomatitis;
Anorexia;
Ulcer formation in the lining of the mouth, throat, esophagus, stomach or intestine;
Pigmentation of the inner lining of the mouth;
Conjunctivitis;
keratitis;
Bronchospasm.

Overdose

Since doxorubicin is administered only by specialized personnel, it is very unlikely that an overdose of drug will be administered.

The possible symptoms that could arise following an overdose are:

Inflammation of stomach and intestine;
Myelosuppression;
Heart problems.

Action mechanism

Doxorubicin has its cytotoxic (cell toxic) action through two mechanisms:

It is able to interlace within the double strand of DNA. In this way, a DNA-drug complex is formed that inhibits cell division. However, this mechanism is not sufficient to kill malignant cells;
It is able to inhibit topoisomerase type II. This enzyme has the ability to cut and weld the two strands that make up DNA and plays a key role in the cell replication process. Once the enzyme is inhibited, the cell is no longer able to divide and undergoes the mechanism of programmed cell death called apoptosis.

Mode of Use - Posology

Doxorubicin is available for intravenous and intravesical (or intravesical) administration. It appears as a red liquid.

Intravenous doxorubicin can be administered via three different routes:

Through a cannula (a thin tube) that is inserted into a vein of an arm or hand;
Through a central venous catheter that is inserted subcutaneously into a vein near the clavicle;
Through the PICC line (Peripherally Inserted Central Catheter), in this case, the catheter is inserted into a peripheral vein, usually of an arm. This technique is used for the administration of anticancer drugs for a prolonged time.

Intravesical administration, on the other hand, occurs by direct instillation into the bladder.

The dosage of doxorubicin must be established by the doctor on an individual basis, depending on the body surface, age and clinical condition of each patient. Furthermore, the dose of drug administered also depends on any other cancer treatments to which the patients have been subjected.

In children, elderly patients, and patients with kidney and / or liver disease, a reduction in the administered dose may be necessary.

Pregnancy and breastfeeding

The use of doxorubicin during pregnancy is not recommended.

Furthermore, both women and men must take adequate precautions to prevent the onset of pregnancies, both during treatment with the drug and for a period of at least six months from the end of the same.

The use of doxorubicin by breastfeeding mothers is not recommended.