Gleevec (imatinib mesylate)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Gastrointestinal stromal tumors (GISTs)
General Information
Gleevec has been approved for the treatment of patients with
positive inoperable and/or metastatic malignant gastrointestinal
stromal tumors (GISTs). This is not the first approval for
Novartis' Gleevec; in May 2001, the drug received approval for
the treatment of chronic myeloid leukemia (CML).
Gleevec is a signal transduction inhibitor that works by
targeting the activity of enzymes called tyrosine kinases. The
activity of one of these tyrosine kinases, known as c-kit, is
thought to drive the growth and division of most GISTs.
Clinical Results
Gleevec's approval was supported by data from an open-label,
multinational study conducted in subjects with unresectable or
metastatic malignant GISTs. In the trial, 147 subjects were
randomized to receive 400 mg or 600 mg orally q.d. for up to 24
months. Subjects in the trial were between 18 and 83 years of age,
and they had a pathologic diagnosis of Kit-positive unresectable
and/or metastatic malignant GIST. Results showed an overall
response rate of 38% (400mg=33%; 600mg=43%) based on confirmed
partial responses at the time of data cut-off for submission.
Side Effects
In the GIST clinical trial, the most common adverse events
included the following:
- Edema
- Nausea
- Diarrhea
- Abdominal pain
- Muscle cramps
- Fatigue
- Rash
Additionally, seven subjects in the trial were reported to have
gastrointestinal bleeds and/or intratumoral bleeds.
Mechanism of Action
Imatinib is an inhibitor of the receptor tyrosine kinases for
platelet-derived growth factor (PDGF) and stem cell factor (SCF),
c-kit, and inhibits PDGF- and SCF-mediated cellular events. In
vitro, imatinib inhibits proliferation and induces apoptosis in
GIST cells, which express an activating c-kit mutation. (from
Gleevec Prescribing Information).
Additional Information
The brand name Gleevec is used in the United States, whereas the
drug is referred to as Glivec outside the United States.
For additional information on Gleevec, please visit
www.gleevec.com.