Anlotinib is an oral medication categorized as a multi-targeted tyrosine kinase inhibitor, primarily employed in the treatment of various cancers. It works by interfering with specific pathways that support tumor growth and spread, disrupting the biological processes cancer cells rely upon for their survival and proliferation.
Mechanism of Action
Anlotinib functions as a tyrosine kinase inhibitor (TKI), blocking the activity of certain proteins called tyrosine kinases. These kinases act like switches inside cells, regulating processes such as cell growth, division, and the formation of new blood vessels. By inhibiting these switches, anlotinib disrupts signals that cancer cells use to multiply and sustain themselves.
A primary way anlotinib exerts its effect is by inhibiting angiogenesis, the process by which tumors develop new blood vessels to acquire nutrients and oxygen. It achieves this by targeting receptors like Vascular Endothelial Growth Factor Receptor (VEGFR) 1, 2, and 3. Disrupting these receptors effectively cuts off the tumor’s supply lines, limiting its ability to grow and spread.
The drug also targets Fibroblast Growth Factor Receptor (FGFR) 1, 2, 3, and 4, Platelet-Derived Growth Factor Receptor (PDGFR) alpha and beta, and c-Kit. These targets play roles in tumor cell growth, survival, and migration. By acting on multiple pathways, anlotinib offers a broad approach to slowing tumor progression.
Approved Uses and Cancers Treated
Anlotinib has received approval from China’s National Medical Products Administration (NMPA) for treating several advanced cancers. It is approved as a third-line treatment for advanced non-small cell lung cancer, soft tissue sarcoma, small cell lung cancer, medullary thyroid carcinoma, and differentiated thyroid cancer.
Beyond its approvals in China, anlotinib has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for rare conditions. This designation was granted for soft tissue sarcoma in 2017 and for ovarian cancer in 2015.
Orphan Drug Designation is granted by the FDA to encourage drug development for rare diseases affecting fewer than 200,000 people in the U.S. This provides incentives for pharmaceutical companies to invest in research and development for these diseases. The designation helps address unmet medical needs for patients with uncommon illnesses.
Administration and Dosage
Anlotinib is an oral medication, available in capsule form. Patients typically take the drug once daily for two consecutive weeks, followed by a one-week rest period. This 2-week on, 1-week off schedule constitutes one treatment cycle.
The available capsule strengths include 8 mg, 10 mg, and 12 mg. The initial dosage, along with the specific length of the treatment cycle, is determined by a treating oncologist. This decision is based on an individual patient’s medical condition, their tolerance to the medication, and how they respond to the therapy.
Common and Serious Side Effects
Patients taking anlotinib may experience a range of side effects, some of which are common and generally manageable. Hypertension, or high blood pressure, is frequently reported, affecting approximately 42% to 64.6% of patients. Hand-foot syndrome, characterized by redness, swelling, and pain on the palms and soles, occurs in about 28.33% to 79.31% of individuals.
Fatigue is another common side effect, with reported incidences ranging from 11.5% to 46.3%. Diarrhea also affects a notable number of patients, appearing in about 23.33% to 34.48% of cases. Other common reactions include hyperlipidemia, elevated thyroid-stimulating hormone, nausea, vomiting, constipation, anemia, leukopenia, thrombocytopenia, proteinuria, and skin rash.
Some side effects can be more serious and warrant immediate medical attention. Bleeding events have been reported, including gingival bleeding. These less common events require prompt assessment by a healthcare professional.
There is also a risk of blood clots (arterial thromboembolism), which has been linked to the mechanism of vascular endothelial growth factor (VEGF) pathway inhibitors like anlotinib. This risk is sometimes related to other side effects such as hyperlipidemia, which can contribute to plaque formation.
Gastrointestinal perforation, a rare but severe complication, has been observed with other tyrosine kinase inhibitors. It is a recognized concern for drugs that interfere with VEGF, as this can affect blood vessel integrity in the gastrointestinal tract. Patients should report any sudden or severe abdominal pain, fever, or signs of bleeding to their healthcare team without delay.
Investigational Uses and Clinical Trials
Due to its multi-targeted mechanism, anlotinib is being explored for its potential against various other cancer types in ongoing research. Scientists are conducting clinical trials to assess its effectiveness and safety in conditions beyond its currently approved indications. This active scientific exploration aims to expand the therapeutic reach of the drug.
Anlotinib has shown encouraging results in studies involving renal cell carcinoma, a type of kidney cancer. Research is also underway to investigate its role in treating gastric cancer and esophageal squamous cell carcinoma. These studies represent efforts to determine if anlotinib can offer new treatment options for a broader range of patients in the future.