Mechanism of action of platinum drugs
Platinum anticancer drugs are cell cycle non-specific drugs that enter the body and act on cellular DNA, including 4 processes:
①Transmembrane transport into cells;
②A dissociation reaction occurs within the cell to generate hydrated ions;
③Migrate to target DNA;
④ Coordinates with DNA to form Pt-DNA adduct, hindering DNA synthesis.
The development history of platinum drugs
Since the first generation of platinum-based antitumor drug cisplatin was launched in the United States in 1978, the research and development of new platinum-based drugs has gone through nearly 40 years of development.
In 1844, chemist Peyrone successfully synthesized cis-PtCl 2 (NH 3 ) 2. In 1965, American biophysics professor Rosenberg and others discovered that the compound (NH 4 ) 2 PtCl 6 could inhibit bacterial division, and subsequently reported cisplatin It has potential anti-cancer activity. In December 1978, the US FDA approved cisplatin for the treatment of testicular cancer. Subsequently, the US National Cancer Institute cooperated with Bristol-Myers Squibb Company to expand the application scope of cisplatin. Cisplatin is used as a treatment for lung cancer, ovary First-line treatment drugs for cancer, head and neck cancer, gastric cancer and other tumors are widely used in clinical practice. Currently, they are still adjuvant treatment for germ cell tumors and non-small cell lung cancer, first-line treatment for advanced bladder cancer and advanced head and neck cancer, and radiotherapy. The first-choice drug for combined treatment of locally advanced cervical cancer, “Expert Consensus on the Clinical Application of Hyperthermic Intraperitoneal Chemotherapy for Gynecological Malignant Tumors”, “Chinese Expert Opinions on the Diagnosis and Treatment of Peritoneal Metastasis of Colorectal Cancer”, “Expert Opinions on Intraoperative Chemotherapy for Colorectal Cancer” and other domestic consensuses are Mention the application of intraperitoneal cisplatin. Cisplatin has strong nephrotoxicity, hematological toxicity, and neurotoxicity.
The difference between cisplatin and carboplatin
Cisplatin
Cisplatin is one of the drugs of choice for the treatment of small cell and non-small cell lung cancer, head and neck tumors, bladder cancer, testicular cancer, and ovarian cancer.
Cisplatin is a first-line drug for a variety of solid tumors and can be used as a radiotherapy sensitizer. It has considerable curative effect and broad anti-cancer spectrum.
Adverse reactions:
1) The most serious form is renal toxicity, which manifests as renal tubular damage, hematuria, and increased serum creatinine 1 to 2 weeks after taking the drug.
Daily dosage >90 mg/m2 requires vigilance for kidney damage, and there are currently no other preventive measures except hydration.
Even at doses with optimal anticancer activity, renal toxicity can ensue. It usually occurs 10 to 15 days after medication, and is mostly reversible.
2) Severe gastrointestinal reactions: Acute vomiting may occur 1 to 2 hours after taking the drug, lasting for 1 week. Nausea and vomiting are the main limiting toxicities, and powerful antiemetics are required.
3) Ototoxicity: It is related to the total dosage of the drug and manifests as tinnitus, rubber plasticizer deafness, and irreversible high-frequency hearing loss. Cisplatin is contraindicated in patients with otitis media. Combined use with aminoglycoside antibiotics (streptomycin, gentamicin, etc.) can cause fatal renal failure and deafness.
4) Myelosuppression is mild: the incidence of leukopenia with cisplatin is 27%. The incidence rate can reach 40% at a dose of ≥120 mg/m2. It also overlaps with the bone marrow toxicity of other anti-cancer drugs in combination chemotherapy. Caution is required when white blood cells <3.5×109/L and platelets <75×109/L.
Carboplatin
Carboplatin can be used as the first choice treatment drug for five types of tumors: small cell and non-small cell lung cancer, ovarian cancer (epithelial), blastoma, and hepatoblastoma. It can also be used as a treatment for bladder cancer, endometrial cancer, It is the second-choice treatment drug for 8 types of tumors: cervical cancer, germ cell cancer, renal cancer, head and neck cancer, neuroblast cancer, and retinoblast carcinoma.
It can also be used for digestive system tumors, liver cancer, etc. and radiation-enhanced treatment.
There is incomplete cross-resistance with cisplatin, and patients who have been ineffective with cisplatin in the past may still achieve curative effect by switching to carboplatin.
Carboplatin has no obvious nephrotoxicity, but the renal function status before treatment can significantly affect the degree of thrombocytopenia caused by carboplatin. Thrombocytopenia is more common in patients with low glomerular filtration rate (GFR) before treatment, so researchers It has been recommended to adjust the carboplatin dose according to GFR to achieve maximum efficacy and avoid intolerable toxicity.
The retention time in the body is shorter than that of cisplatin, so the gastrointestinal reactions of carboplatin are milder and less common than those of cisplatin, and can be recovered after stopping the drug for 1 to 2 weeks.
Carboplatin’s nephrotoxicity is mild and uncommon, and ototoxicity and neurotoxicity are rare; however, myelosuppression is stronger than that of cisplatin and is dose-limiting. Hydration is not required before treatment, but concurrent use of aminoglycosides can increase nephrotoxicity and ototoxicity.
Carboplatin has a strong bone marrow suppression effect, which not only reduces white blood cells, but also causes a higher incidence of thrombocytopenia.
The thrombocytopenia was severe, with the lowest point occurring at 2 to 3 weeks and recovery at the 4th week after treatment. Nausea and vomiting are common, usually appearing 6 to 12 hours after treatment and disappearing within 24 hours.
Summary
To put it simply, cisplatin has good efficacy when applied to a variety of tumors. However, due to the significant nephrotoxicity of potassium hydroxide, hydration and diuresis are required before use. Other adverse reactions are also serious, so it is generally used in Cancer patients with good basic physical conditions.
Carboplatin has milder adverse reactions than cisplatin, but its anti-tumor effect is also slightly weaker than cisplatin. It has a narrow anti-cancer spectrum and is insensitive to esophageal and bladder tumors.
