What is the risk of hepatotoxicity associated with Carboplatin (carboplatin) therapy?

From the Guidelines

Carboplatin can cause liver injury, though it is less hepatotoxic than many other chemotherapy agents, with liver toxicity typically presenting as mild, transient elevations in liver enzymes (AST, ALT) occurring in approximately 15-20% of patients, as seen in studies such as 1.

Liver Injury from Carboplatin

• The incidence of severe hepatotoxicity is rare, occurring in less than 1% of cases.
• Patients receiving carboplatin should have liver function tests monitored before each treatment cycle and periodically during therapy, as recommended by guidelines such as 1 and 1.
• Risk factors for carboplatin-induced liver injury include pre-existing liver disease, concurrent hepatotoxic medications, and higher cumulative doses.

Management of Liver Injury

• If significant liver enzyme elevations occur (greater than 3 times the upper limit of normal), dose reduction or temporary discontinuation may be necessary, as suggested by studies such as 1.
• The mechanism of carboplatin hepatotoxicity involves direct cellular damage through DNA cross-linking and oxidative stress in hepatocytes.
• Unlike cisplatin, carboplatin has a more favorable toxicity profile due to its slower rate of conversion to active metabolites, as noted in 1.

Patient Advice

• Most cases of liver injury resolve with dose adjustment or discontinuation, and permanent liver damage is uncommon.
• Patients should be advised to avoid alcohol and other hepatotoxic substances during treatment to minimize additional liver stress, as recommended by general medical guidelines.

Clinical Considerations

• The performance status of the patient is a major determinant in the selection of a regimen, with regimens having lower toxicity profiles recommended in patients with compromised liver or renal status or serious comorbid conditions, as seen in 1.
• Carboplatin may be substituted for cisplatin in the metastatic setting for cisplatin-ineligible patients, such as those with a GFR <60 mL/min, as suggested by studies such as 1.

From the FDA Drug Label

High dosages of carboplatin, USP (more than four times the recommended dose) have resulted in severe abnormalities of liver function tests. The anticipated complications of overdosage would be secondary to bone marrow suppression and/or hepatic toxicity.

• Liver Injury: The FDA drug label indicates that high dosages of carboplatin can result in severe abnormalities of liver function tests, suggesting a potential for liver injury, particularly at doses exceeding four times the recommended amount 2.
• Hepatic Toxicity: Overdosage of carboplatin may lead to hepatic toxicity, as stated in the drug label 2. Given the information provided, it is clear that carboplatin can cause liver injury, especially at high doses.

From the Research

Carboplatin Liver Injury

• Carboplatin is a platinum-based chemotherapy drug that can cause liver injury, among other side effects 3.
• The dose-limiting side effect for carboplatin is myelosuppression, but it can also cause hepatotoxicity, which is a type of liver injury 3.
• A case report described a patient who developed acute fulminant liver failure after receiving a combination therapy of carboplatin, pemetrexed, and pembrolizumab for metastatic lung cancer 4.
• The study highlights the importance of monitoring liver function in patients receiving carboplatin and other chemotherapy drugs.
• Abnormal liver function tests can be caused by various factors, including liver disease, and require careful interpretation and management 5, 6.
• In older adults, elevated liver enzymes and declined albumin levels can be associated with metabolic syndrome and increased mortality, respectively 6.
• Clinicians should consider individual patient risk factors when assessing abnormal liver function tests and managing liver disease 6.