Gleevec

General Information | Side Effects | Drug Interactions (adult site)

The most important improvement in the treatment of adult GIST has been the development of highly effective new drugs. Gleevec is the first drug approved (in 2002) specifically for GIST treatment. Although the data is still limited, Gleevec may be less effective for children, since pediatric GISTs do not usually have the mutations that Gleevec targets at the molecular level. In addition, there are other kinase inhibitors that appear to inhibit wild-type KIT (the most common type in pediatric GIST) better than Gleevec. See Activated KIT remains a target in wild-type and pediatric GIST. In addition, trials testing another type of drug that inhibits the IGF1R pathway are being planned for pediatric GIST. It is too early to know how well these drugs will work or what the side effects in children will be.

Because Gleevec is usually still the first drug tried in pediatric GIST, some information about Gleevec will be presented.

Based on the striking results of phase II clinical trials in adult GIST, Gleevec® was filed for registration and received approval from the European Union (EU), the Food and Drug Administration (FDA) in the United States, and other countries for the treatment of adult patients with c-Kit (CD117)–positive unresectable and/or metastatic malignant GISTs.

Gleevec® is known by several different names:

• Gleevec® in the U.S.
• Glivec® outside the U.S.
• Imatinib Mesylate.
• STI571 when it was in clinical trials (STI stands for Signal Transduction Inhibitor).

Gleevec is a pill that is taken either once or twice daily, depending on the dose.

Gleevec is different from traditional chemotherapy in that it is very selective. Traditional chemotherapy kills all cells that are dividing quickly. This is what causes so many of the side effects of traditional chemotherapy. In addition to the cancer cells, this type of chemotherapy also kills many of the bodies normal cells. Gleevec is much more selective and as a result has fewer side effects. It was designed to block the activity of a mutant type of enzyme (an enzyme is a specific type of protein) that causes Chronic Myeloid Leukemia (CML). This enzyme is called Bcr/Abl. In addition to blocking Bcr/Abl, Gleevec also blocks several other enzymes (enzymes are a type of protein). These are:

• KIT.
• Platelet Derived Growth Factor Receptors (PDGFR-alpha and PDGFR-beta).
• Various forms of the Abl enzymes.

The KIT receptor belongs to a class of receptors called the tyrosine kinase family. It is estimated that the human genome will reveal more than 400 tyrosine kinases . Because Gleevec selectively blocks only a few of these tyrosine kinases, it is both effective and has fewer side effects than traditional chemotherapy.

For normal signal transduction to occur in the KIT receptor, a chemical called ATP (adenosine triphosphate) must bind to a site in the kinase domain of the receptor. Gleevec prevents signal transduction of KIT by binding to this ATP binding site. This prevents the transfer of phosphate groups from ATP and blocks signal transduction in normal and mutated forms of KIT.

New: Gleevec is introduced in a tablet form

• New Gleevec® 400mg and 100mg tablets are replacing the 100mg capsules to make therapy more convenient for all patients
• If you have been taking Gleevec capsules, you might be concerned about switching to tablets. It is natural to feel that way
• It is important for you to understand that you will receive exactly the same medicine in the new Gleevec tablets that you have come to know

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Glivec (Gleevec outside the U.S.)

Gleevec (Glivec outside the US) Gleevec is an effective treatment that has been approved in many countries for GIST. In a phase II trial of Gleevec for 147 adult GIST patients, 54% obtained a partial response (over 50% shrinkage of tumors), 28% had minor response (less than 50% shrinkage) or stable disease, and only 14% showed primary resistance to the drug.10 In a EORTC Phase I trial, the response rate was 69%, 77% were still on treatment at 18 months, and 66% were progression free at 18 months.

For more information about Gleevec, call your doctor, see the full Prescribing Information, or call the Gleevec Hotline at 1-877-GLEEVEC (1-877-453-3832).