Bleomycin is a glycopeptide antibiotic with cytostatic properties. It is used for squamous cell carcinoma, Hodgkin’s and non-Hodgkin’s lymphomas, testicular tumors, and malignant pleural effusions. Specific side effects associated with bleomycin therapy, especially with overdose, include pulmonary fibrosis and skin damage.
What is bleomycin?
The drug bleomycin is a cytostatic drug that damages human DNA by causing DNA strand breaks. Two structurally similar glycopeptides exist in the bleomycin mixture, derivatives Bleomycin A2 and B2, with derivative A2 having a higher percentage of 55-70%. The active ingredient is obtained from the actinomycete Streptomyces verticillus, which places it in the group of antibiotics.
Pharmacological effects on the body and organs
Bleomycin is administered either intravenously (through the vein), intramuscularly (into the muscle), or intrapleurally (into the chest cavity), depending on the disease. After intravenous drug administration, elimination in blood plasma occurs rapidly and is biphasic. Initially, the half-life is 24 minutes and then increases to 2 to 4 hours. The substance is inactivated via hydrolases and other low-molecular-weight protein fractions, which occur primarily in blood plasma but also in the liver. In the lungs and skin, however, these hydrolyses occur to a lesser extent. Bleomycin is ultimately excreted by the kidney, but cannot be removed by dialysis. The formation of superoxide radical anions is the main mechanism in the action of bleomycin. It forms a bleomycin-iron (II) complex in the cell with iron (II) ions, resulting in intercalation (intercalation) into DNA. In addition, molecular oxygen binds to the iron (II) ion, and an electron is donated to the oxygen. Thus, activation of bleomycin follows to form a bleomycin-iron-(III) complex and superoxide radical ions are formed simultaneously. The superoxide radical ions give rise to hydroxyl radicals (OH-), which lead to single-strand breaks in the DNA helix. At increased doses, double-strand breaks occur. The cell cycle is specifically aborted in the G2 phase (i.e. shortly before the phase of actual cell division), which is why translocation (change of location) of the chromosomes occurs. Since bleomycin can in principle act in all cells of the body, an unintended mutagenic effect in other organs during treatment cannot be ruled out. The genetic material can also be damaged by bleomycin therapy, so that men should not father children for up to 6 months after appropriate therapy. Sperm preservation should be considered before starting therapy, as permanent infertility may result. Women should not become pregnant during therapy.
Medicinal use and use for treatment and prevention.
Bleomycin is used primarily in combination with other chemotherapeutic agents. Areas of use include squamous cell carcinomas of the head, neck, external genitalia, and cervix, and testicular tumors. In addition, the drug is administered in the early stages of Hodgkin’s lymphoma and in adults with non-Hodgkin’s lymphoma of intermediate or high-grade malignancy. As monotherapy, bleomycin is used palliatively for malignant (malignant) pleural effusions.
Risks and Side Effects
A test dose of 1 mg should be given before the initial use of bleomycin, and the patient should be observed for at least 4 hours to rule out serious immediate reactions. In particular, a severe allergic reaction is feared in lymphoma patients and may result in severe febrile seizures with fatality. In general, the following side effects may occur: Nausea, vomiting, stomatitis (inflammation of the oral mucosa), loss of appetite, joint and muscle pain, and chills and high fever. Specifically, bleomycin toxicity primarily affects the lungs and skin. A particular and serious side effect of bleomycin is pulmonary fibrosis, which can develop from chronic pneumonia. Pulmonary fibrosis can occur, especially at total doses above 300 mg, making it dose-limiting. Previous irradiation of the lungs or chest, increased oxygen administration during bleomycin therapy, and age over 70 years additionally increase the risk of pulmonary fibrosis. Furthermore, skin toxicity exists in the form of hyperkeratosis, peeling of the skin and ulceration.Most likely, this side effect is caused by the decreased activity of bleomycin hydrolase, which the drug deactivates. Bleomycin should not be used during breastfeeding. In pregnancy, it may be used only if there is a life-threatening condition of the patient. This may result in damage to the unborn child. In the case of acute pneumonia, severe pulmonary dysfunction, pre-irradiated lungs, as well as liver and kidney dysfunction, a strict indication should be made, as the risk of suffering severe side effects is significantly increased in these cases. Live vaccines should not be administered during bleomycin therapy, as this may result in severe infectious disease. In addition, antibody formation and thus the efficacy of inactivated vaccines, for example, as part of the annual influenza vaccination, may be reduced during cytostatic therapy.
