Are there serious side effects of Cabozantinib? What should you pay attention to while taking it?

Cabozantinib (trade names include Cabometyx and Cometriq) is a multi-target tyrosine kinase inhibitor (TKI) that mainly acts on VEGFR and MET, AXL and other signaling pathways are widely used in the treatment of renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), medullary thyroid carcinoma (MTC) and other malignant tumors. Although cabozantinib has shown good anti-tumor activity in clinical practice, it also has a complex and extensive side effect spectrum due to its multiple targets. Therefore, patients need to pay close attention to adverse reactions during medication and adjust medication strategies based on individual conditions.

1. Common side effects and mechanisms of cabozantinib

The side effects of cabozantinib are mainly related to its interference with angiogenic pathways and other growth factors. Common adverse reactions include:

1.Gastrointestinal reactions: such as diarrhea, nausea, vomiting, stomatitis, and loss of appetite. These reactions are relatively common, and about more than 50% of patients will experience varying degrees of diarrhea. The mechanism may be related to TKI's inhibition of intestinal epithelial cell renewal and damage to the intestinal microenvironment.

2.Skin toxicity: including hand-foot syndrome (skin redness, swelling, peeling, and pain on the hands and feet), rash, dryness, hair loss, etc. Skin toxicity may seriously affect the quality of life of some patients. TKI drugs that inhibit VEGFR and EGFR will affect skin repair and sweat gland function.

3. Fatigue and weakness: It is one of the most common systemic side effects of cabozantinib treatment and can affect the ability to perform daily activities. The mechanism is unclear and may be related to metabolic changes and the tumor itself.

4.High blood pressure and bleeding risk: Due to the inhibition of VEGFR, cabozantinib can cause vasoconstriction and damage to endothelial function, leading to an increase in blood pressure and even bleeding tendencies, including gum bleeding, gastrointestinal bleeding, etc.

5.Proteinuria and renal function abnormalities:TKI drugs can damage glomerular filtration function, and long-term use may cause proteinuria or mild renal function decline. Regular urine routine and creatinine levels need to be monitored regularly.

6.Abnormal liver function: such asAST, ALTIncrease, especially in the treatment of liver cancer, more attention should be paid to changes in liver function. Medication should be used with extreme caution in the context of liver cirrhosis.

2. Precautions when taking cabozantinib

In order to maximize the therapeutic effect of cabozantinib and reduce the risk of side effects, patients need to pay attention to the following aspects during use:

1. Follow your doctor’s instructions on taking medications and dietary requirements

Cabotinib is taken orally in tablet form and is recommended to be taken on an empty stomach - at least 2 hours before meals or 1 hours after meals to avoid affecting drug absorption. Patients should not change the dosage or stop taking the medicine on their own. Especially when side effects occur, they should contact their doctor for evaluation and adjustment in time, rather than discontinuing the medicine without authorization.

2. Monitor physical signs and experimental indicators regularly

Blood pressure: Monitor once a week at the beginning of treatment, and can be extended to once a month later. If hypertension is found, antihypertensive treatment should be initiated promptly.

Liver and kidney function and electrolytes: Check once every 2-4 weeks to monitor changes in ALT, AST, creatinine, urine protein, electrolytes, etc.

Thyroid function: Some patients may develop hypothyroidism, especially those with previous thyroid disease, and their TSH levels should be checked regularly.

3. Side effects management and dose adjustment

Mild side effects (such as Grade 1~2 diarrhea and fatigue): usually can be relieved by symptomatic and supportive treatment such as taking antidiarrheal drugs or increasing rest time.

Moderate and severe side effects (such as Grade 3 hand-foot syndrome, severe diarrhea): Cabozantinib medication needs to be suspended, and the dose will be reduced as appropriate to resume treatment after symptoms are relieved.

Intolerable or serious adverse reactions (such as hypertensive crisis, obvious bleeding, gastrointestinal perforation, etc.): The drug should be discontinued immediately and permanently, and emergency treatment should be carried out.

4. Combined medication and dietary taboos

Avoid strong potenciesCYP3A4inhibitors (such as ketoconazole, clarithromycin) or inducers (such as rifampicin), otherwise it will affect the plasma concentration of cabozantinib.

Avoid grapefruit and its juice, which inhibitCYP3A4, significantly increasing the systemic exposure of cabozantinib and increasing the risk of toxicity.

Pay attention to replenishing sufficient fluids to prevent electrolyte imbalance and dehydration, especially when diarrhea occurs, body fluid management should be paid more attention to.

3. Medication precautions for special groups of people

1. The elderly: reduced metabolic capacity, poor tolerance to drugs, and higher incidence of side effects. Blood pressure, electrolytes, and performance status should be monitored more frequently during medication.

2. Patients with hepatic dysfunction: Patients with mild to moderate liver dysfunction may adjust the dosage as appropriate, while those with severe liver dysfunction should be used with caution or even banned.

3.Pregnant and lactating women: Cabozantinib may cause teratogenic risks to the fetus and is contraindicated during pregnancy. Effective contraceptive measures must be taken during use, and breastfeeding is not recommended.

4.Preoperative and postoperative patients: Because cabozantinib will inhibit wound healing, it is recommended to stop taking cabozantinib at least 28 days before surgery. It is also necessary to wait for the wound to heal before resuming the drug after surgery.

Cabozantinib, as a broad-spectrum multi-target tyrosine kinase inhibitor, has shown good efficacy in multiple cancer types, especially against advanced renal cancer, liver cancer and medullary thyroid cancer. But at the same time, it has many types of side effects and a high incidence rate, so it needs to be used rationally under the guidance of a professional doctor. By standardizing medication, regular monitoring, timely dose adjustment and handling of adverse reactions, most patients can tolerate cabozantinib treatment and benefit from it. In the future, with the accumulation of clinical experience and the development of personalized medicine, the application of cabozantinib will be safer and more efficient.

Reference materials:https://www.drugs.com/