chemistry

Lapatinib

Lapatinib is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Lapatinib rather than just read about it. In short: Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) (trade names Tykerb and Tyverb marketed by Novartis) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways.

Key takeaways

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

Reference excerpt

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) (trade names Tykerb and Tyverb marketed by Novartis) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

Status In March 2007, the U.S. Food and Drug Administration (FDA) approved lapatinib in combination therapy for breast cancer patients already using capecitabine (Xeloda). In January 2010, Tykerb received accelerated approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses the HER2 receptor and for whom hormonal therapy is indicated (in combination with letrozole). Pharmaceutical company GlaxoSmithKline (GSK) markets the drug under the proprietary names Tykerb (mostly U.S.) and Tyverb (mostly Europe and Russia). The drug currently has approval for sale and clinical use in the US, Australia, Bahrain, Kuwait, Venezuela, Brazil, New Zealand, South Korea, Switzerland, Japan, Jordan, the European Union, Lebanon, India and Pakistan. In August 2013, India's Intellectual Property Appellate Board revoked the patent for Glaxo's Tykerb citing its derivative status, while upholding at the same time the original patent granted for lapatinib. The drug lapatinib ditosylate is classified as S/NM (a synthetic compound showing competitive inhibition of the natural product) that is naturally derived or inspired substrate.

Mode of action

Biochemistry Lapatinib inhibits the tyrosine kinase activity associated with two oncogenes, EGFR (epidermal growth factor receptor) and HER2/neu (human EGFR type 2). Over expression of HER2/neu can be responsible for certain types of high-risk breast cancers in women. Like sorafenib, lapatinib is a protein kinase inhibitor shown to decrease tumor-causing breast cancer stem cells. Lapatinib inhibits receptor signal processes by binding to the ATP-binding pocket of the EGFR/HER2 protein kinase domain, preventing self-phosphorylation and subsequent activation of the signal mechanism (see Receptor tyrosine kinase#Signal transduction).

Clinical application

Breast cancer Lapatinib is used as a treatment for women's breast cancer in treatment-naïve, ER+/EGFR+/HER2+ breast cancer patients and in patients who have HER2-positive advanced breast cancer that has progressed after previous treatment with other chemotherapeutic agents, such as anthracycline, taxane-derived drugs, or trastuzumab (Herceptin). A 2006 GSK-supported randomized clinical trial on female breast cancer previously being treated with those agents (anthracycline, a taxane and trastuzumab) demonstrated that administrating lapatinib in combination with capecitabine delayed the time of further cancer growth compared to regimens that use capecitabine alone. The study also reported that risk of disease progression was reduced by 51%, and that the combination therapy was not associated with increases in toxic side effects. The outcome of this study resulted in a somewhat complex and rather specific initial indication for lapatinib—use only in combination with capecitabine for HER2-positive breast cancer in women whose cancer have progressed following previous chemotherapy with anthracycline, taxanes and trastuzumab. Early clinical trials have been performed suggesting that high dose intermittent lapatinib might have better efficacy with manageable toxicities in the treatment of HER2-overexpressing breast cancers.

Adverse effects Like many small molecule tyrosine kinase inhibitors, lapatinib is regarded as well tolerated. The most common side effects reported are diarrhea, fatigue, nausea and rashes. Of note, lapatinib related rash is associated with improved outcome. In clinical studies elevated liver enzymes have been reported. QT prolongation has been observed with the use of lapatinib ditosylate but there are no reports of torsades de pointes. Caution is advised in patients with hypokalaemia, hypomagnesaemia, congenital long QT syndrome, or with coadministration of medicines known to cause QT prolongation. In combination with capecitabine, reversible decreased left ventricular function are common (2%).

Ongoing trials in gastric cancer Phase III study designed to assess lapatinib in combination with chemotherapy for advanced HER2-positive gastric cancer in 2013 failed to meet the primary endpoint of improved overall survival (OS) against chemotherapy alone. The trial did not discover new safety signals, while the median OS for patients in the lapatinib and chemotherapy group was 12.2 months against 10.5 months for patients in the placebo plus chemotherapy. Secondary endpoints of the randomized, double-blinded study, were progression-free survival (PFS), response rate and duration of response. Median PFS was 6 months, response rate was 53% and the duration of response was 7.3 months in the investigational combination chemotherapy group compared to median PFS of 5.4 months, response rate of 39% and duration of response of 5.6 months for patients in chemotherapy alone group. Diarrhoea, vomiting, anemia, dehydration and nausea were serious adverse events (SAE) reported in over 2% of patients in the investigational combination chemotherapy group, while vomiting was the most common SAE noted in the chemotherapy group.

References

External links "Lapatinib Ditosylate". NCI Drug Dictionary. National Cancer Institute. "Lapatinib Ditosylate". National Cancer Institute. 16 March 2007.

Illustrations

Worked examples

Example 1 — a first encounter with Lapatinib

Start with the simplest possible case. Write down what Lapatinib claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, 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 Lapatinib 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 Lapatinib 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 Lapatinib

In research: Lapatinib appears in chemistry 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 Lapatinib 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: Lapatinib is common in secondary-school and first-year university syllabi. It links to neighbouring topics 3-Fluorophenyl compounds, Anilines, Antineoplastic drugs, so understanding it makes those chapters shorter.
In everyday life: Look for Lapatinib 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.

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How to study Lapatinib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Lapatinib 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 Lapatinib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Lapatinib in simple terms?

Why does Lapatinib matter?

Because it connects several chemistry 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 Lapatinib?

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 Lapatinib.