Vatalanib (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

, codenamed PTK787 or PTK/ZK) is a small molecule

protein kinase inhibitor A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate, or PO4, group) to a protein and can modulate its function. The phospha ...

that inhibits

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

. It is being studied as a possible treatment for several types of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, particularly cancer that is at an advanced stage or has not responded to

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

. Vatalanib is orally active, that is, it is effective when taken by mouth. Vatalanib is being developed by Bayer Schering and

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

. It inhibits all known

VEGF receptors VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inhi ...

, as well as

platelet-derived growth factor receptor Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular ...

-beta and c-kit, but is most selective for

VEGFR-2 Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) also known as vascular endothelial growth factor receptor 2 (VEGFR-2) is a VEGF receptor. ''KDR'' is the human gene encoding it. KDR has also been designated as CD309 (cluste ...

Development

Vatalanib was discovered through high-throughput screening. Retrieved on October 29, 2008. It has been extensively investigated in

Phase I Phase 1, Phase I or Phase One may refer to: Media * Marvel Cinematic Universe: Phase One, six American superhero films from 2008–2012 * ''Phase One'' (Art Ensemble of Chicago album), 1971 * ''Phase One'' (Saga album), 1998 * ''Phase One'', r ...

, II and

III III or iii may refer to: Companies * Information International, Inc., a computer technology company * Innovative Interfaces, Inc., a library-software company * 3i, formerly Investors in Industry, a British investment company Other uses * Ins ...

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s. Two large, randomized controlled Phase III trials have studied the effect of adding vatalanib to the FOLFOX

chemotherapy regimen A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combinat ...

in people with metastatic

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

: CONFIRM-1, whose participants had not yet received any treatment for their cancer; and CONFIRM-2, in which participants had received

first-line treatment A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...

with

irinotecan Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cispl ...

and fluoropyrimidines. Vatalanib produced no significant improvement in overall survival (the

primary endpoint Clinical endpoints or clinical outcomes are outcome measures referring to occurrence of disease, symptom, sign or laboratory abnormality constituting a target outcome in clinical research trials. The term may also refer to any disease or sign tha ...

of the studies), although it did significantly increase progression-free survival in CONFIRM-2. Both trials found that progression-free survival was improved in people with high levels of lactate dehydrogenase, an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

used as a marker of tissue breakdown; the reasons for and implications of this difference are still unclear.

Adverse effects

The adverse effects of vatalanib appear similar to those of other VEGF inhibitors. In the CONFIRM trials, the most common side effects were

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, gastrointestinal upset (

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, and

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

Notable users

Patrick Swayze, a popular actor in the 1980s who starred in such films as

Dirty Dancing ''Dirty Dancing'' is a 1987 American romantic drama dance film written by Eleanor Bergstein, produced by Linda Gottlieb, and directed by Emile Ardolino. Starring Patrick Swayze and Jennifer Grey, it tells the story of Frances "Baby" Houseman ...

and Road House was given this drug when he was diagnosed with Stage IV Pancreatic Cancer in 2008. Doctors hoped the drug would cut off blood supply to the tumor. Despite this, Swayze died on September 14, 2009, 20 months after being diagnosed.

References

External links

Ongoing and completed clinical trials of vatalanib
at ClinicalTrials.gov (U.S.

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

) {{Chemotherapeutic agents Angiogenesis inhibitors Tyrosine kinase inhibitors Experimental cancer drugs