pharmachologic effect
Cisplatin (cis-diamindichloroplatinum) is an anticancer drug containing the heavy metal platinum.
Cisplatin has properties similar to those of bifunctional alkylating agents that form interstrand and intrastrand crosslinks in DNA, thereby disrupting its function, which leads to cell death; while the drug does not have cyclic and phase specificity. It has immunosuppressive and radiosensitizing properties.
Pharmacokinetics
After a rapid intravenous infusion (15 minutes – 1 hour), the appearance of cisplatin in the blood plasma and the peak of its concentration is determined immediately after administration. With intravenous infusion over 6-24 hours, the plasma concentration of the drug increases gradually during the infusion, reaching a maximum by the end of administration.
Cisplatin is characterized by extensive distribution in body fluids and tissues; while the highest concentrations are achieved in the kidneys, liver and prostate gland. Platinum released from cisplatin rapidly binds to tissue and plasma proteins. 2 hours after the end of the three-hour infusion, 90% of the platinum in the plasma is in a protein-bound state. Cisplatin has the ability to accumulate in the body and be found in some tissues for another six months after the last dose of the drug. Biotransformation of cisplatin is carried out by rapid non-enzymatic transformation with the formation of inactive metabolites. Only cisplatin, which is not bound to proteins, or its platinum-containing metabolites, has a cytotoxic effect.
The half-life of total platinum has a very wide individual variability and ranges from 2-72 hours in healthy people, and 1-240 hours in severe renal failure. Cisplatin is excreted primarily in the urine. Cisplatin can be removed from the systemic circulation by dialysis, but only during the first 3 hours after drug administration.
Cisplatin, commonly used in combination chemotherapy regimens, is widely used in the treatment of the following solid tumors:
germ cell tumors of women and men;
ovarian and testicular cancer;
lung cancer;
head and neck tumors
In addition, cisplatin has antitumor activity in the following types of tumors:
cervical cancer;
bladder cancer;
osteosarcomas;
melanoma;
neuroblastoma;
esophageal carcinoma.
Dosing regimen
Cisplatin can be used both as monotherapy and in combination with other cytostatics in various doses, depending on the therapy regimen. Individual selection of the dose should be guided by the data of special literature.
Cisplatin is administered intravenously or when indicated (intraperitoneal tumors) in the abdominal cavity.
Cisplatin in monotherapy or in combination with other chemotherapy drugs is administered at a dose of 50-100 mg / m2 as an intravenous infusion every 3-4 weeks or 15-20 mg / m2 intravenously drip daily for 5 days every 3-4 weeks .
In order to stimulate diuresis (up to 100 ml / h) and to minimize the nephrotoxic effect of the drug, hydration is carried out. Before the introduction of Cisplatin, up to 2 liters of liquid (0.9% sodium chloride solution or 5% dextrose solution) is dripped intravenously. After the end of the infusion, 400 ml of 0.9% sodium chloride solution or 5% dextrose solution is additionally injected. Abundant fluid intake and maintenance of diuresis must be observed for 24 hours. If intensive hydration is not sufficient to maintain adequate diuresis, an osmotic diuretic (eg, mannitol) can be administered.
Cisplastin is administered intravenously by drip at a rate of not more than 1 mg/min. Long-term infusions are carried out for 6-8-24 hours, provided there is sufficient diuresis before and during the administration of the drug.
Cisplatin is diluted in 0.9% sodium chloride solution to a concentration of 1 mg / ml. Cisplastin lyophysilate should first be dissolved in 10-25 ml of water for injection.
Do not use dextrose (glucose) solutions to dilute Cisplatin.
Note: Since aluminum reacts with and inactivates cisplatin and causes precipitation, it is very important not to use needles or other equipment containing aluminum when preparing and administering cisplatin.
Side effect
From the urinary system: nephrotoxicity (is cumulative and is the main toxic factor limiting the dose of Cisplatin). Kidney lesions that are accompanied by damage to the renal tubules may first be detected in the second week after dosing and manifest as an increase in serum creatinine, urea, uric acid and / or a decrease in creatinine clearance. Renal failure is usually mild to moderate and is reversible with normal doses of cisplatin.
