All About Gleevec (Glivec)
Expert Opinions: KIT & PDGFRA mutations in GIST: A to Z by Michael Heinrich, M.D.
Looking for kinase mutations in GISTs: how, when and why? by Christopher Corless, M.D., PhD.
Based on the striking results of phase II clinical trials, Gleevec was filed for registration and received approval from the European Union (EU) (May 31, 2002), the Food and Drug Administration (FDA) in the United States (February 1, 2002), and other countries for the treatment of adult patients with c-Kit (CD117)positive unresectable and/or metastatic malignant GISTs. On December 19th, 2008, Gleevec was also approved for adjuvant treatment for patients in the United States.
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 body's 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. These are:
- 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.
Gleevec is introduced in a tablet form
- Gleevec 400mg and 100mg tablets have replaced the 100mg capsules to make therapy more convenient for all patients.
- 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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Gleevec (Glivec outside the U.S.)
Gleevec is a new, effective treatment that has recently been approved in many countries for GIST. In a phase II trial of Gleevec for 147 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. In an 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. The differences in response rate may be related to differences in measuring or interpreting response by the institutions involved. These impressive response rates to a previously unresponsive cancer makes Gleevec the preferred treatment for metastatic or inoperable GIST.
For more information about Gleevec; explore the links at the top of this page, call your doctor, see the full Prescribing Information, or call the Gleevec Hotline at 1-877-GLEEVEC (1-877-453-3832).