Main Research Findings

Pexidartinib is the first drug approved in the USA for patients with tenosynovial giant cell tumor (TGCT). 3 The ENLIVEN study showed that pexidartinib effectively shrinks tumor size and improves symptoms and functionality in patients with TGCT who are unable to undergo surgery due to tumor location and/or size. However, 1 and 2 highlight a significant safety concern: liver toxicity (hepatotoxicity). This potential side effect requires close monitoring with liver function tests before, during, and after treatment.

Reasons for Side Effects

Pexidartinib belongs to a class of drugs called tyrosine kinase inhibitors. These drugs work by blocking a specific protein (CSF1R) involved in cell growth, thereby inhibiting tumor growth. This mechanism of action can also affect various cells, including liver cells, leading to hepatotoxicity.

Common Side Effects

Hair Color Changes

3 indicates that hair color changes are a common side effect of pexidartinib. This may be due to pexidartinib affecting cells involved in melanin production in hair.

Fatigue

3 also mentions fatigue as a common side effect of pexidartinib. This may be linked to pexidartinib potentially affecting cellular energy metabolism.

Hepatotoxicity

1 and 2 state that pexidartinib can cause liver function abnormalities. This side effect often appears within the first two months of treatment and can become severe, potentially life-threatening. Therefore, regular liver function tests are crucial during pexidartinib treatment for early detection and management of this side effect.

Managing Side Effects

Liver Function Tests

2 emphasizes the importance of regular liver function tests before, during, and after pexidartinib treatment. This helps in early detection and prompt management of liver toxicity.

Dosage Adjustments

1 suggests that dosage adjustments or temporary treatment cessation may be necessary if hepatotoxicity occurs. The appropriate course of action depends on the severity of the side effect.

Comparison of Studies

Commonalities

Multiple studies indicate that pexidartinib is effective in treating TGCT. They also consistently report liver toxicity as a significant side effect.

Differences

The studies differ in aspects such as pexidartinib administration methods, patient populations, and assessment approaches, leading to some variations in results. For example, 3 's ENLIVEN study involved a randomized controlled trial on patients with surgically challenging TGCT to evaluate pexidartinib's effectiveness and safety. In contrast, 1 provided a broader review of hepatotoxicity associated with various tyrosine kinase inhibitors.

Real-Life Applications: Things to Keep in Mind

Pexidartinib is a viable treatment option for patients with surgically challenging TGCT. However, understanding the risk of liver toxicity and ensuring appropriate monitoring with regular liver function tests are crucial. Decisions regarding treatment continuation or cessation should be made in consultation with a physician based on liver function test results and side effect severity.

Current Research Limitations

Further research is needed to understand the long-term safety and effectiveness of pexidartinib. A deeper understanding of the mechanisms underlying hepatotoxicity and potential preventive measures is also required.

Future Research Directions

Research into new drugs and therapies to mitigate pexidartinib-induced liver toxicity is essential. Establishing personalized dosage and monitoring approaches for individual patients is another crucial area of focus.

Conclusion

Pexidartinib is an effective treatment for surgically challenging TGCT, but it carries the risk of liver toxicity. Close monitoring with liver function tests is crucial when using this drug to ensure early detection of side effects. Decisions regarding treatment continuation or cessation should be made in consultation with a physician. Future research holds promise for further elucidating the safety and efficacy of pexidartinib.