What is the risk of Paclitaxel (Taxol) induced hepatotoxicity?

From the Guidelines

Taxol can cause liver injury, and patients receiving it should have their liver function tests (LFTs) monitored before each treatment cycle, with dose adjustments or discontinuation if significant elevations occur, as evidenced by the risk ratio of grade 3-4 elevated liver enzymes being 1.56 [1.22; 2.01] in patients treated with chemotherapy + immunotherapy combinations 1. When considering Taxol-induced liver injury, it's essential to note that the risk of elevated liver enzymes is increased, with a risk ratio of 1.56 [1.22; 2.01] compared to chemotherapy alone 1. The liver injury pattern is typically hepatocellular, with elevated transaminases occurring in patients. Some key points to consider in managing Taxol-induced liver injury include:

• Monitoring liver function tests (LFTs) before each treatment cycle
• Dose adjustments or discontinuation if significant LFT elevations occur
• Avoiding alcohol and hepatotoxic medications during treatment
• Educating patients to report symptoms like jaundice, dark urine, right upper quadrant pain, or unusual fatigue immediately to their healthcare provider
• Considering alternative formulations like nab-paclitaxel (Abraxane) for patients with pre-existing liver disease, as it may be better tolerated due to the absence of Cremophor EL 1.

From the FDA Drug Label

Hepatic: No relationship was observed between liver function abnormalities and either dose or Schedule of paclitaxel administration Among patients with normal baseline liver function 7%, 22%, and 19% had elevations in bilirubin, alkaline phosphatase, and AST (SGOT), respectively. Prolonged exposure to paclitaxel was not associated with cumulative hepatic toxicity. Hepatic necrosis and hepatic encephalopathy leading to death have reported

Taxol induced liver injury is a potential risk, as evidenced by reports of hepatic necrosis and hepatic encephalopathy leading to death. However, no relationship was observed between liver function abnormalities and either dose or schedule of paclitaxel administration. Elevations in bilirubin, alkaline phosphatase, and AST (SGOT) were reported in some patients, but prolonged exposure to paclitaxel was not associated with cumulative hepatic toxicity 2.

• Hepatic necrosis and hepatic encephalopathy are rare but serious adverse events associated with paclitaxel use.
• Liver function tests should be monitored in patients receiving paclitaxel, especially those with pre-existing liver disease.
• The risk of liver injury should be weighed against the potential benefits of paclitaxel therapy in individual patients 2.

From the Research

Taxol Induced Liver Injury

• Taxol, also known as paclitaxel, is a chemotherapeutic agent used to treat various types of cancer, including breast, ovarian, and lung cancer.
• Paclitaxel has been associated with liver injury, including elevated liver enzymes and bilirubin levels, as reported in studies such as 3 and 4.
• A rare case of paclitaxel-induced acute hepatic necrosis has been reported in the literature, as described in 5.
• Impaired liver function has been shown to affect paclitaxel toxicity, with patients having impaired liver function being at a higher risk of developing hematological toxicity, as reported in 6.
• However, paclitaxel has also been shown to have antifibrotic effects in a rat model of liver fibrosis, as reported in 7, suggesting a potential therapeutic role in the treatment of liver fibrosis.

Mechanism of Liver Injury

• The exact mechanism of paclitaxel-induced liver injury is not fully understood, but it is thought to be related to the drug's metabolism in the liver and its effects on liver cells.
• Paclitaxel is primarily metabolized in the liver by the cytochrome P450 enzyme system, and impaired liver function can lead to increased levels of the drug in the body, as reported in 4.
• The drug's effects on liver cells, including the induction of apoptosis and inflammation, may also contribute to liver injury, as reported in 5.

Clinical Implications

• Patients with impaired liver function may require dose modifications or alternative treatments to minimize the risk of paclitaxel-induced liver injury, as reported in 6.
• Monitoring of liver function tests, including liver enzymes and bilirubin levels, is recommended in patients receiving paclitaxel, as reported in 3.
• Further research is needed to fully understand the mechanisms of paclitaxel-induced liver injury and to develop strategies for preventing and treating this condition, as reported in 7.