The active substance cisplatin belongs to the cytostatic drugs. It is used to treat malignant cancers.
What is cisplatin?
Cisplatin (cis-diammine dichloridoplatin) is a cytostatic drug that inhibits the growth of cancer cells. The drug forms an inorganic platinum-containing heavy metal compound and has a complex-bound platinum atom. Cisplatin is in the form of orange-yellow crystals or a yellow powder. It is difficult to dissolve in water. The cytostatic effects of platinum complexes were discovered by accident in the 1960s. The American chemist Barnett Rosenberg (1926-2009) was investigating what effect alternating current had on the bacterial species Escherichia coli. For this purpose, Rosenberg resorted to platinum electrodes. The experiment revealed cell growth inhibitory effects. Research revealed that this property did not result from the alternating current, but was due to the complex compound cis-diaminetetrachloridoplatin(IV) that resulted from the platinum electrodes. Further experiments confirmed the growth inhibitory effect. It was not until 1974 that cisplatin was used for the first time in the treatment of cancer. In a study at Indiana State University Hospital, the compound was used to treat testicular cancer. In the further course, the drug resulted in positive treatment successes without a relapse of the cancer. In Germany, cisplatin was used under the preparation name Cis-GRY. In addition, numerous generics entered the market.
Pharmacologic action
Cisplatin has the property of inhibiting the production of genetic material such as DNA. In this process, the drug attaches itself indiscriminately to all DNA building blocks and cross-links the individual strands senselessly. The mechanism of action is thought to occur independently of the cell life cycle. To a lesser extent, cisplatin also interferes with the production of proteins that are of vital importance to the cell. Due to the senseless cross-linking of the DNA strands, the DNA information can only be read incorrectly or even not at all. In this way, cisplatin inhibits the division of the cells, which ultimately results in their destruction. Cisplatin is administered intravenously. When the substance is distributed, it also crosses the blood–brain barrier. Organs where the cytostatic drug preferentially accumulates include the intestines, liver, kidneys and male testes. The excretion of cisplatin as well as its metabolites occurs primarily through the urine. The remainder is excreted by bile.
Medical use and application
As a single agent or together with other cytostatic agents, cisplatin is administered for the treatment of advanced cancers. This is true even if metastases (daughter tumors) have already formed as a result of the tumor. The most common indications include prostate cancer, testicular cancer, bladder cancer, esophageal cancer, head and neck tumors, cervical cancer, ovarian cancer, lung cancer, black skin cancer, squamous cell carcinoma, pancreatic cancer, and osteosarcoma, which is a malignant bone tumor. Cisplatin is administered by infusion. In most cases, it is combined with other chemotherapeutic agents. The dosage is usually 15 to 20 milligrams of cisplatin per day per square meter of body surface area. Higher dosages, such as 80 to 120 mg per square meter of body surface area, are also possible. Cisplatin treatment of children can be carried out in principle. In this case, the physician adjusts the dose to the child’s body.
Risks and side effects
The use of cisplatin is not free of side effects. For example, the cytostatic drug often causes diarrhea, nausea, and vomiting. However, this unpleasant side effect can be relatively well controlled by the administration of modern antiemetics. In addition, cisplatin has a negative effect on the cells of organs such as the kidneys. This side effect can be partially counteracted by the cytoprotectant amifostine. Other common side effects include changes in the blood count such as a deficiency of white blood cells and platelets, anemia (anemia), sodium deficiency, fever, an excess of uric acid, palpitations, cardiac arrhythmias, a slowing of the heartbeat, blood poisoning (sepsis), respiratory problems, and inflammation of the blood vessels at the injection site.Occasionally, hypersensitivity reactions such as reddening of the skin, hives, skin rashes or itching, hearing disorders, painful swelling of the chest, ovulation disorders, malformation of male sperm, magnesium deficiency, and deposits of metal in the gums may also occur. In seniors and children, hearing disorders sometimes take on significant proportions. Because cisplatin can cause severe disturbances in kidney function, the treating physician promotes urine excretion. To this end, he adds two liters of an appropriate solution to the drug, as well as a drainage preparation such as mannitol. Cisplatin must not be administered if the patient is hypersensitive to the active substance or other platinum-containing compounds. The same applies to renal dysfunction, dehydration of the body, pre-existing hearing impairment and bone marrow dysfunction. If the patient also suffers from nerve dysfunction, the physician must carefully decide between the risks and benefits of cisplatin therapy. Under no circumstances should the cytostatic drug be administered during pregnancy, as it can have fatal effects on the unborn child. In addition, there is a risk of later cancer of the child. For this reason, consistent contraceptive measures should be taken during treatment, which applies to both female and male patients. In addition, cisplatin can lead to permanent infertility. Female patients must refrain from breastfeeding their child during therapy, as the active ingredient can pass into breast milk.
