Major Research Findings

Lenvatinib, a multi-receptor tyrosine kinase inhibitor with anti-angiogenic activity, has become the standard treatment for radioiodine-refractory metastatic differentiated thyroid cancer. While lenvatinib has been shown to significantly improve progression-free survival, it is associated with a high incidence of toxicity. 18 This toxicity can lead to dose reductions, interruptions, or even complete withdrawal of lenvatinib, compromising its anti-tumor efficacy.

Lenvatinib has been approved for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas, but the SELECT trial revealed a significant adverse event profile that may limit its use in clinical practice. 2

Lenvatinib is emerging as a key new targeted therapy in the treatment of hepatocellular carcinoma (HCC). Studies show that this drug, combined with conventional therapies, can potentially improve the prognosis of patients with HCC. 12

Lenvatinib may be an effective drug for treating advanced thymic carcinoma. 13 reported a case of successful complete surgical resection after administering lenvatinib as first-line therapy.

Lenvatinib, when used in combination with radiation therapy for the treatment of advanced follicular thyroid cancer, may increase the risk of developing a tracheoesophageal fistula. 5

Lenvatinib can cause gastrointestinal perforation. This is a serious side effect of lenvatinib that can be fatal and has been reported in several patients. 8

Combining lenvatinib with conventional treatments may enhance its effectiveness in treating HCC. 15 demonstrated that combining lenvatinib with TACE was more effective than combining sorafenib with TACE.

Lenvatinib side effects may be linked to patient genotype. 1 found that the risk of developing lenvatinib side effects is associated with polymorphisms in genes like CYP3A4 and ABCB1.

Blood pressure control within the first eight weeks of treatment with lenvatinib is essential and can affect the maintenance of dosage. 3

The combination of lenvatinib, anti-PD-1 antibodies, and drug-eluting bead transarterial chemoembolization (DEB-TACE) may prove effective in treating unresectable HCC. 10

Lenvatinib can cause skin ulcers. reports a case of multiple skin ulcers associated with lenvatinib.

Lenvatinib can lead to thromboembolic events, which are rare but more likely to occur in patients with predisposing factors. 17

Reasons for Side Effects

Lenvatinib is a multi-kinase inhibitor with anti-angiogenic activity, meaning it inhibits the function of various proteins involved in angiogenesis, which helps to suppress cell growth and metastasis. However, lenvatinib's anti-angiogenic effect can also affect normal blood vessels, leading to side effects.

The side effects of lenvatinib vary depending on individual patient factors like genotype, body constitution, dosage, and concurrent medications. Side effects can also change over time.

Common Side Effects

High Blood Pressure

Lenvatinib can cause high blood pressure. This can occur early in treatment. High blood pressure can be managed by reducing the lenvatinib dose or by taking antihypertensive medications. 18 , 14 , 3

Diarrhea

Lenvatinib can cause diarrhea. This can be managed by reducing the lenvatinib dose or by taking anti-diarrheal medications. 18 , 1

Hand-Foot Syndrome

Lenvatinib can cause hand-foot syndrome. This is characterized by redness, pain, and a rash on the hands and feet. It can be managed by reducing the lenvatinib dose. 18 , 13

Mouth Sores

Lenvatinib can cause mouth sores. This can be managed by reducing the lenvatinib dose or by taking antifungal medications. 1

Weight Loss

Lenvatinib can cause weight loss. This can be managed by reducing the lenvatinib dose or by consuming a high-calorie diet. 1

Gastrointestinal Perforation

Lenvatinib can cause gastrointestinal perforation. This is a rare but serious side effect that may require discontinuing lenvatinib. 8

Thromboembolic Events

Lenvatinib can cause thromboembolic events. These are rare but serious and may require discontinuing lenvatinib. 17

Skin Ulcers

Lenvatinib can cause skin ulcers, which may require discontinuing lenvatinib.

Side Effect Management

Managing High Blood Pressure

Lenvatinib-induced high blood pressure can be managed by taking antihypertensive medications. 18 , 3

Managing Diarrhea

Lenvatinib-induced diarrhea can be managed by taking anti-diarrheal medications. 18

Managing Hand-Foot Syndrome

Lenvatinib-induced hand-foot syndrome can be managed by reducing the lenvatinib dose. 18

Managing Mouth Sores

Lenvatinib-induced mouth sores can be managed by taking antifungal medications. 1

Managing Weight Loss

Lenvatinib-induced weight loss can be managed by consuming a high-calorie diet. 1

Managing Gastrointestinal Perforation

Lenvatinib-induced gastrointestinal perforation may require discontinuing lenvatinib. 8

Managing Thromboembolic Events

Lenvatinib-induced thromboembolic events may require discontinuing lenvatinib. 17

Managing Skin Ulcers

Lenvatinib-induced skin ulcers may require discontinuing lenvatinib.

Comparison Across Studies

Commonalities in Studies

Many studies show that lenvatinib can cause various side effects, including high blood pressure, diarrhea, and hand-foot syndrome. Additionally, studies indicate that lenvatinib side effects vary depending on individual patient factors such as genotype, body constitution, dosage, and concurrent medications.

Differences Across Studies

Studies demonstrate varying rates and severity of lenvatinib side effects. This is likely due to differences in the patient populations and research methodologies employed. Moreover, the side effects of lenvatinib have been shown to change over time.

Real-Life Application Notes

Lenvatinib is a drug with the potential for various side effects. Therefore, it's essential to fully understand the risks and benefits associated with lenvatinib before using it. Regular doctor's appointments during lenvatinib use are crucial for early detection of any potential side effects. If you experience suspected side effects like high blood pressure, diarrhea, or hand-foot syndrome while taking lenvatinib, consult your doctor immediately. Severe side effects may necessitate discontinuing lenvatinib.

Current Research Limitations

Research on the side effects of lenvatinib is still limited. Further research is needed to gain a better understanding of these side effects. In particular, further research is required to understand how lenvatinib side effects are influenced by patient factors like genotype, body constitution, dosage, and concurrent medications.

Future Research Directions

Development of new therapies to mitigate the side effects of lenvatinib is necessary. There is also a need to develop biomarkers that can predict the occurrence of lenvatinib side effects.

Conclusion

Lenvatinib is an effective drug for treating radioiodine-refractory metastatic differentiated thyroid cancer but can cause various side effects. It's crucial to understand the risks and benefits associated with lenvatinib before using it. Regular doctor's appointments during lenvatinib use are essential for early detection of any potential side effects. If you have concerns about lenvatinib side effects, consult your doctor immediately.