Tivozanib

Key takeaways

Tivozanib belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Tivozanib to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Tivozanib from memory before moving on to harder problems.

Reference excerpt

Tivozanib, sold under the brand name Fotivda, is a medication used for the treatment of advanced renal cell carcinoma (kidney cancer). It is an oral VEGF receptor tyrosine kinase inhibitor. The most common side effects include fatigue (tiredness), hypertension (high blood pressure), diarrhea, decreased appetite, nausea, dysphonia (voice changes), hypothyroidism, cough, and stomatitis. Tivozanib was approved for medical use in the European Union in August 2017, and in the United States in March 2021.

Medical uses In the United States, tivozanib is indicated for the treatment of adults with relapsed or refractory advanced renal cell carcinoma following two or more prior systemic therapies. In the European Union, it is indicated for the treatment of adults with advanced renal cell carcinoma; and for the first line treatment of adults with advanced renal cell carcinoma and for adults who are VEGFR and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced renal cell carcinoma.

Contraindications Tivozanib must not be combined with St. John's Wort, an inducer of the liver enzyme CYP3A4. It should not be taken during pregnancy as it is teratogenic, embryotoxic and fetotoxic in rats.

Adverse effects The most common side effects in studies were hypertension (high blood pressure, in 48% of patients), dysphonia (hoarse voice, 27%), fatigue and diarrhea (both 26%). A hypertensive crisis occurred in 1% of patients.

Interactions Administration of a single dose of tivozanib with rifampicin, a strong inducer of the enzyme CYP3A4, cuts the biological half-life and total exposure (area under the curve) of tivozanib in half, but has no relevant influence on highest concentrations in the blood. Combination with ketoconazole, a strong CYP3A4 inhibitor, has no relevant effects. The clinical significance of these findings is not known.

Pharmacology

Mechanism of action A quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor (VEGF). It is designed to inhibit all three VEGF receptors.

Pharmacokinetics After tivozanib is taken by mouth, highest blood serum levels are reached after 2 to 24 hours. The total area under the curve is independent of food intake. When in the bloodstream, over 99% of the substance are bound to plasma proteins, predominantly albumin. Although the enzymes CYP3A4 and CYP1A1 and several UGTs are capable of metabolising the drug, over 90% circulate in unchanged form. The metabolites are demethylation, hydroxylation and N-oxidation products and glucuronides. The biological half-life is 4.5 to 5.1 days; 79% being excreted via the feces, mostly unchanged, and 12% via the urine, completely unchanged.

Chemistry Tivozanib is used in form of the hydrochloride monohydrate, which is a white to light brown powder. It is practically insoluble in water and has low solubility in aqueous acids, ethanol and methanol. It is not hygroscopic and not optically active.

History It was discovered at Kyowa Kirin and developed by Aveo Pharmaceuticals. The US Food and Drug Administration (FDA) approved tivozanib based on evidence from one clinical trial of 350 adult participants with advanced kidney cancer (renal cell carcinoma) that had been treated with two or more prior medicines and has come back or did not respond to treatment. The trial compared participants who were randomly assigned to receive either tivozanib or sorafenib. Both the participants and the health care providers knew which treatment was being given. The treatment continued until the disease progression or the side effects became too toxic. The trial compared the length of time participants were alive without progression between the two groups. The trial was conducted at 120 of sites in 12 of countries in North America and Europe. The number of participants representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.

Clinical trials Phase III results on advanced renal cell carcinoma suggested a 30% or 3 months improvement in median progression-free survival compared to sorafenib but showed an inferior overall survival rate of the experimental arm versus the control arm. The Food and Drug Administration's Oncologic Drugs Advisory Committee voted in May 2013 13 to 1 against recommending approval of tivozanib for renal cell carcinoma. The committee felt the drug failed to show a favorable risk-benefit ratio and questioned the equipose of the trial design, which allowed control arm patients who used sorafenib to transition to tivozanib following progression disease but not those on the experimental arm using tivozanib to transition to sorafenib. The application was formally rejected by the FDA in June 2013, saying that approval would require additional clinical studies. In 2016, Aveo Oncology announced the start of a second Phase III clinical study in third line advanced RCC patients.

Society and culture

Legal status In August 2017, the European Commission approved tivozanib for medical use in the European Union.

References

External links Clinical trial number NCT02627963 for "A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)" at ClinicalTrials.gov

Illustrations

Worked examples

Example 1 — a first encounter with Tivozanib

Start with the simplest possible case. Write down what Tivozanib claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Tivozanib before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Tivozanib ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Tivozanib

In research: Tivozanib appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Tivozanib in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Tivozanib is common in secondary-school and first-year university syllabi. It links to neighbouring topics Angiogenesis inhibitors, Cancer treatments, Chloroarenes, so understanding it makes those chapters shorter.
In everyday life: Look for Tivozanib outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Tivozanib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Tivozanib means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Tivozanib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Tivozanib in simple terms?

Tivozanib, sold under the brand name Fotivda, is a medication used for the treatment of advanced renal cell carcinoma (kidney cancer). It is an oral VEGF receptor tyrosine kinase inhibitor.

Why does Tivozanib matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Tivozanib?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Tivozanib.