Cabozantinib is a targeted therapy used to treat specific cancers, including hepatocellular carcinoma (HCC). It interferes with processes that support cancer growth and spread within the body. This medication offers a treatment option for individuals dealing with this challenging liver cancer. The following sections will explain HCC, how cabozantinib works, its applications, and practical considerations for managing therapy and side effects.
Understanding Hepatocellular Carcinoma
Hepatocellular carcinoma, often referred to as HCC, stands as the most common type of primary liver cancer in adults. This form of cancer originates in the liver’s main cells, known as hepatocytes, and is a significant cause of cancer-related deaths globally. The development of HCC is strongly linked to chronic liver conditions, particularly cirrhosis, which involves severe scarring of the liver tissue.
Common causes of cirrhosis that can lead to HCC include long-term infections with hepatitis B or hepatitis C viruses. Other contributing factors involve chronic heavy alcohol consumption, non-alcoholic fatty liver disease (NASH) linked to obesity and diabetes, and certain inherited liver diseases such as hemochromatosis. These conditions promote abnormal cell growth in the liver.
Symptoms of HCC can be subtle in early stages, often mirroring those of underlying liver disease. As the cancer progresses, individuals might experience unexplained weight loss, loss of appetite, upper abdominal pain, or a feeling of fullness. Other signs can include nausea, vomiting, fatigue, and jaundice, which is a yellowing of the skin and eyes.
Diagnosis of HCC involves a physical examination and various medical tests. Blood tests may check for alpha-fetoprotein (AFP), a protein that can be elevated in liver cancer. Imaging techniques like ultrasound, CT scans, and MRI are used to visualize tumors in the liver. Sometimes, a liver biopsy confirms the diagnosis. Effective treatments are important for managing this aggressive cancer.
How Cabozantinib Works
Cabozantinib functions as a multi-targeted receptor tyrosine kinase inhibitor, meaning it blocks the activity of specific proteins called tyrosine kinases that play a role in cancer development. These kinases act like switches, signaling cancer cells to grow, divide, and form new blood vessels that feed the tumor. By inhibiting these signals, cabozantinib aims to slow down or stop cancer progression.
The medication primarily targets several key receptor tyrosine kinases, notably vascular endothelial growth factor receptor 2 (VEGFR2), MET, and AXL. VEGFR2 is particularly involved in angiogenesis, the process by which new blood vessels form to supply tumors with nutrients and oxygen. By blocking VEGFR2, cabozantinib can starve the tumor by disrupting its blood supply.
MET, or mesenchymal-epithelial transition factor, is another significant target. Activation of MET pathways is frequently observed in various cancers, including HCC, and is associated with tumor growth, invasiveness, and the spread of cancer cells to other parts of the body, a process known as metastasis. Inhibiting MET helps to counteract these aggressive features of the cancer.
AXL, or anexelekto, is a receptor tyrosine kinase that also contributes to tumor growth, survival, and metastasis. It has been identified as a mechanism that can lead to resistance against other therapies that target VEGFR. By simultaneously inhibiting AXL, cabozantinib offers a broader approach to disrupting cancer pathways and potentially overcoming drug resistance.
When Cabozantinib is Used for HCC
Cabozantinib is typically considered for individuals with advanced hepatocellular carcinoma, particularly after their disease has progressed following prior systemic therapies. Its approval for HCC treatment is specifically for patients who have already received sorafenib, another oral multikinase inhibitor. This positions cabozantinib as a second-line or even third-line treatment option in the management of advanced HCC.
The medication’s use in this context is supported by findings from the CELESTIAL trial, a large phase 3 study. This trial enrolled patients with unresectable HCC who had experienced disease progression after at least one previous systemic treatment, including sorafenib. The study demonstrated that cabozantinib improved overall survival and progression-free survival compared to a placebo.
Cabozantinib is recommended for patients with advanced HCC who maintain good liver function, often classified as Child-Pugh class A. While most patients in clinical trials had this level of liver function, its effectiveness has been observed across various patient and disease characteristics. This makes it a suitable option for patients whose cancer has continued to advance despite initial treatments.
Cabozantinib offers an additional therapeutic avenue for patients with advanced HCC, especially when other treatments have not been successful. It can potentially extend survival and delay disease progression in this challenging patient population.
Managing Cabozantinib Treatment and Side Effects
Cabozantinib is administered as an oral medication, taken once daily. Patients take the tablet at least one hour before or two hours after eating to ensure proper absorption. Adhering to the prescribed schedule and dosage is important for effectiveness.
Treatment with cabozantinib can be associated with several side effects, requiring careful monitoring and management by a healthcare team. Common side effects include fatigue, diarrhea, and a decrease in appetite. Diarrhea can be frequent and may require anti-diarrheal medications or dietary adjustments.
Another notable side effect is palmar-plantar erythrodysesthesia, often called hand-foot skin reaction, which can cause redness, swelling, pain, or blistering on the palms of the hands and soles of the feet. This dermatological reaction can sometimes be severe and may necessitate dose adjustments or temporary interruptions of treatment. Regular skin checks and moisturizing can help manage these symptoms.
High blood pressure, or hypertension, is also a frequently reported side effect. Patients should have their blood pressure regularly checked and managed with medication if necessary. Other potential side effects include nausea, vomiting, and changes in liver function tests.
Less common, but serious, side effects can include hemorrhages, blood clots, and gastrointestinal perforations or fistulas. Patients should promptly report any signs of severe abdominal pain, unusual bleeding, or symptoms like severe headaches or vision changes to their healthcare provider. Open communication with the medical team about any new or worsening symptoms is important.
Managing these side effects often involves dose modifications, such as reducing the daily dose or temporarily stopping the medication, rather than discontinuing treatment entirely. Regular check-ups with the healthcare provider are necessary to assess treatment response, monitor for side effects, and adjust the treatment plan as needed. This approach helps to maximize the benefits of cabozantinib while minimizing its associated challenges.