What is Tivozanib used for?

Tivozanib, sold under the trade name Fotivda, is a potent, selective inhibitor of vascular endothelial growth factor receptors (VEGFR) developed primarily for the treatment of advanced renal cell carcinoma (RCC). This small-molecule tyrosine kinase inhibitor (TKI) targets all three VEGF receptors (VEGFR-1, VEGFR-2, and VEGFR-3), which play a crucial role in angiogenesis—the process through which new blood vessels form from pre-existing vessels. By inhibiting these receptors, Tivozanib restricts the blood supply to cancerous cells, thereby inhibiting tumor growth and progression.

Tivozanib has been under extensive research and development, with pivotal studies conducted by AVEO Oncology and later by EUSA Pharma, which now holds the marketing rights. The U.S. Food and Drug Administration (FDA) granted approval for Tivozanib in March 2021 after a series of clinical trials demonstrated its efficacy and safety in patients with RCC. Notably, Tivozanib is also being investigated for potential applications in treating other cancers, such as hepatocellular carcinoma and colorectal cancer, indicating its broad therapeutic potential.

The mechanism of action for Tivozanib is centered around its ability to selectively inhibit VEGF receptors. VEGF is a signal protein produced by cells that stimulate the formation of blood vessels. In many cancers, VEGF is overexpressed, leading to increased vascular permeability and promoting tumor growth. Tivozanib binds to VEGFR-1, VEGFR-2, and VEGFR-3 with high affinity, blocking the VEGF pathway. This inhibition results in reduced endothelial cell proliferation, migration, and survival. Consequently, the drug effectively starves the tumor of the necessary blood supply needed for its growth and survival. The high selectivity of Tivozanib for VEGF receptors minimizes off-target effects, which can be a significant advantage over other VEGFR inhibitors that may have broader targets and thus more side effects.

Administering Tivozanib is relatively straightforward. The medication is available in oral capsule form, making it convenient for outpatient treatment. The standard dosage is typically 1.34 mg taken once daily for 21 consecutive days, followed by a 7-day rest period, constituting a 28-day cycle. It is essential that patients adhere to this schedule to maximize the drug's efficacy while minimizing potential side effects. The onset time for therapeutic effects can vary among individuals, but clinical studies indicate that patients often begin to see results within the first few treatment cycles. It is crucial to follow the prescribing healthcare provider's instructions closely and attend all scheduled appointments to monitor the drug's impact and make any necessary adjustments.

Like all medications, Tivozanib comes with a range of possible side effects. The most common adverse reactions include hypertension, fatigue, diarrhea, decreased appetite, and dysphonia (voice changes). These side effects are generally manageable and can often be mitigated with supportive care measures. However, more severe side effects can occur, such as proteinuria (high levels of protein in the urine), heart failure, and hemorrhagic events. It's imperative to monitor for these conditions regularly during treatment. Patients with pre-existing cardiovascular conditions should use Tivozanib with caution, as the drug can exacerbate issues related to blood pressure and heart function.

Contraindications for Tivozanib use include a history of severe hypersensitivity to the drug or any of its components. Pregnant women should not use Tivozanib due to the potential risk of harm to the developing fetus, and effective contraception should be used by both men and women during treatment and for at least one month following the last dose. Additionally, due to the risk of severe adverse reactions, the use of Tivozanib in patients with uncontrolled hypertension is contraindicated.

Interactions with other drugs are an important consideration when prescribing Tivozanib. Concomitant use of strong CYP3A4 inhibitors, such as ketoconazole and itraconazole, can increase Tivozanib plasma concentrations, potentially heightening the risk of toxicity. Conversely, strong CYP3A4 inducers like rifampin and phenytoin can decrease Tivozanib plasma levels, potentially reducing its efficacy. Therefore, it may be necessary to adjust the Tivozanib dose when taken alongside these medications.

Moreover, as Tivozanib can affect blood pressure, combining it with other antihypertensive drugs requires careful monitoring to avoid compounded hypotensive effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) should also be used cautiously, as they can affect kidney function, which could be further compromised by Tivozanib.

In summary, Tivozanib represents a significant advancement in the treatment of advanced renal cell carcinoma, with ongoing research suggesting its potential use in other cancers. Its highly selective inhibition of VEGF receptors marks it as a potent anti-angiogenic agent with a relatively manageable side effect profile. However, careful consideration of drug interactions and contraindications is essential to optimize treatment outcomes and ensure patient safety. As research continues, the therapeutic landscape for Tivozanib is likely to expand, offering new hope for patients with various types of cancer.