Cisplatin: a review of toxicities and therapeutic applications.

Cisplatin is a platinum-based chemotherapy drug used for treating different types of cancer. While it is effective in attacking cancer cells, its widespread use is limited due to significant toxic side effects such as kidney toxicity, gastrointestinal symptoms, bone marrow suppression, ear damage, and nerve damage. The causes of these side effects are not fully understood and ways to prevent them are yet to be established.

Antineoplastic Activity of Cisplatin

• Cisplatin works against cancer by interacting with the DNA in cells, creating cross-links and adducts which disrupt DNA function and ultimately lead to cell death.
• It also induces the generation of superoxide radicals, unstable molecules that can damage cells.
• The effectiveness of cisplatin has been demonstrated in the treatment of various types of cancer in dogs, including osteosarcoma, transitional cell carcinoma, squamous cell carcinoma, melanoma, mesothelioma, carcinomatosis, and germinal cell tumors.
• In horses, cisplatin has been used for treating squamous cell carcinoma and sarcoids.

Adverse Effects and Limitations of Cisplatin

• Cisplatin’s most notorious and potentially most harmful side effect is kidney toxicity, or nephrotoxicity.
• The exact cause of cisplatin-induced nephrotoxicity remains unclear, but several theories have been proposed, indicating complexity in its mechanism.
• Other side effects associated with cisplatin include gastrointestinal symptoms (like nausea, vomiting, diarrhea), bone marrow suppression (leading to decreased production of blood cells), ear damage (ototoxicity which can lead to hearing loss), and nerve damage (neurotoxicity).
• For cats, cisplatin cannot be used due to severe lung edema, a serious condition where fluid accumulates in the lungs.

Managing and Preventing Cisplatin Toxicity

• The most accepted method to prevent cisplatin-induced kidney damage currently is saline diuresis, a procedure that involves infusion of salt solutions to increase urine production and excretion of cisplatin.
• There have been efforts to find alternative strategies, including pharmaceutical interventions and genetic/molecular alterations, that could potentially protect against cisplatin toxicities without requiring long-term diuresis.
• However, no solutions have been found that can effectively protect against all toxic effects of cisplatin.