Actinomycin D is a cytotoxic antibiotic also known as dactinomycin. Because it is a cytostatic drug that inhibits cell growth and division, Actinomycin D is used to treat cancer. In this context, it is available under the trade names Lyovac-Cosmegen and Cosmegen.
What is actinomycin D?
Because Actinomycin D is a cytostatic drug that inhibits cell growth and division, Actinomycin D is used to treat cancer. The peptide antibiotic Actinomycin D is derived from the soil bacteria Streptomyces parvulus. The active ingredient is composed of two cyclic peptides linked by a phenoxazine compound. The cytostatic drug was first described in 1949. Initially, scientists hoped to have found an antibiotic for the treatment of bacterial diseases in Actinomycin D. However, it soon became clear how toxic it was. However, it quickly became apparent how toxic the drug was for human cells as well. As a result, physicians soon began using it instead to treat various tumors. The cytostatic drug is designed to prevent the rapid proliferation of cancer cells during chemotherapy in both adults and children.
Pharmacological action
Actinomycin D binds to the DNA (deoxyribonucleic acid) of cells, preventing the double helix from opening. Experts refer to this process, in which a drug attaches molecules to DNA and crosslinks them, as intercalation. Actinomycin D binds primarily to the guanine residues of the DNA. In this way, Actinomycin D initially inhibits RNA synthesis at low doses. As a result, protein production is minimized in the cells. At higher doses, DNA replication is also affected. The genetic material is therefore no longer replicated, which means that cell division also fails to occur. The tumor is thus inhibited from growing. Since Actinomycin D cannot penetrate the blood–brain barrier in the human body, tumors in the brain and spinal cord cannot be treated with the drug. All other cells in the body that contain DNA can be affected by the drug. This is because actinomycin D does not act specifically on the tumor, but equally on the healthy cells of the body.
Medical application and use
The active ingredient Actinomycin D is used for various solid tumors. Among them, in Ewing’s sarcoma, a fairly common bone cancer in both children and adults. However, physicians also use the cytostatic properties of Actinomycin D in malignant tumors of the soft tissues (soft tissue sarcoma and rhabdomyosarcoma). Similarly, the drug is used in children and adolescents during the treatment of a malignant kidney tumor (nephroblastoma). Adults with testicular carcinoma, chorionic carcinoma, or Kaposi’s sarcoma can also be treated with Actinomycin D. In all of these chemotherapies, Actinomycin D is combined with other cytostatic drugs. It is also administered several times at precisely defined intervals over a longer period of time. This is because about 30 percent of the active ingredient is excreted in the urine and stool after just one week. Because Actinomycin D is highly irritating, it is only given intravenously and cannot be taken orally. Because of the severe tissue damage, physicians control the injection site very carefully during treatment.
Risks and side effects
Because actinomycin D inhibits the growth and division of human cells, it can cause a variety of side effects. For example, the drug interferes with the development of blood cells, among other things. This can lead to a temporary deficiency of platelets and white blood cells. The latter in turn results in an increased incidence of infections caused by bacteria, fungi and viruses. Direct contact with the drug can severely damage and even kill the skin and eyes as well as the connective tissue. Therefore, the injection must only be made into the vein and not into the neighboring tissue. Damage can be particularly severe after prior radiation, which is why Actinomycin D should never be used after radiation therapy. Very often, nausea and vomiting occur a few hours after Actinomycin D administration. Painful mucosal damage (mucositis) in the mouth, esophagus and intestines may also occur. The drug can also attack the liver. As Actinomycin D is mutagenic and embryotoxic, it can cause lasting damage to genetic material and must not be used during pregnancy.
