Doxorubicin is a drug belonging to the anthracycline group of substances, which are used in chemotherapy as cytostatics to treat various types of cancer. The active ingredient belongs to the intercalants.
What is doxorubicin?
Doxorubicin is a cytostatic drug. Cytostatic drugs are substances that inhibit cell division and/or cell growth. Therefore, they are mainly used for the treatment of cancer or autoimmune diseases. Doxorubicin is a so-called hydroxy derivative of the natural antibiotic daunorubicin, which is produced by the bacteria Streptomyces peuceticus and Streptomyces coeruleorubidus. Since the effect of the cytostatic drug is based on intercalation of molecules into DNA, doxorubicin is classified as an intercalant. The substance is administered to the body intravenously or intra-arterially, i.e. via infusion or injection, for the treatment of tumors such as breast carcinoma or bronchial carcinoma.
Pharmacologic action
Doxorubicin binds to the DNA of the body’s cells, where it prevents polymerases, which in turn serve to copy the genetic material, from binding. Through this interference, the drug blocks both the synthesis of DNA and the synthesis of RNA, thereby inhibiting cell division and ultimately causing cell death. In particular, the body’s cells in the S phase are very sensitive to the substance. The S-phase is the replication phase of the cell cycle, in which new DNA synthesis takes place. Since tumor cells divide more frequently, they are affected by the toxic effect of the drug significantly more often than healthy body cells.
Medical application and use
Doxorubicin has a fairly low rate of resistant tumors and is therefore used with other intercalants for almost all solid tumors. These include, for example, cancers of the female breast or bronchial system. Lymphomas are also among the typical indications for doxorubicin. In patients who cannot tolerate potent combined chemotherapy, doxorubicin is also suitable as a monotherapy. For simpler tumor diseases, the drug is administered intravenously, i.e., into a vein. In contrast, hepatocellular carcinoma (HCC), a malignant cancer of the liver cells, requires intra-arterial application as part of transarterial chemoembolization (TACE). Here, the treatment is administered via a special catheter system through the arteries. In this way, the active substance can be applied directly into those vessels that supply the tumor. Chemotherapeutic agents such as doxorubicin are temporarily embolized with iodine-containing oils or starch particles to prolong the effect of the therapeutic agents in the tumor. The embolization agents reduce the blood supply to the tumor and allow the chemotherapy drug to remain in the cancer longer.
Risks and side effects
Among the most significant side effects is bone marrow depression. This is where normal blood formation in the bone marrow, called hematopoiesis, stops. This results in a deficiency of red blood cells, white blood cells, and platelets. As a result, the immune system is significantly weakened, so that those affected suffer more frequently from infections. Thrombocytopenia, the lack of blood platelets, results in an increased risk of bleeding. Patients can develop severe bleeding even from minor injuries. Typical symptoms of anemia include decreased performance and rapid fatigue. Any bone marrow depression is potentially life-threatening. Doxorubicin can be both nephrotoxic and cardiotoxic. Nephrotoxins damage the cells of the kidney and can cause glomerulonephritis. In this bilateral form of kidney inflammation, the renal corpuscles are affected first. Glomerulonephritis is one of the most common causes of chronic renal failure. Cardiotoxic agents, on the other hand, damage the heart muscle. This can result in cardiomyopathy. Such doxorubicin-induced cardiomyopathy can be counteracted even months after the first administration with the administration of dexrazoxane. This agent can reduce the cytotoxic effect of doxorubicin. Ulceration is also among the potential side effects of doxorubicin. The deep-seated substance defects of the skin or mucosa are also called ulcers. Scarless healing of these painful skin manifestations is not possible. In the worst case, severely affected extremities must be amputated.Open wound infections are also among the potential complications.
