What is Glivec?
Glivec is a medicine containing the active substance imatinib. It is available as capsules (50 and 100 mg) and tablets (100 and 400 mg).
What is Glivec used for?
Glivec is an anticancer medicine used to treat the following diseases:
- chronic myeloid leukemia (CML), a white blood cell tumor characterized by the uncontrolled increase of granulocytes (a type of white blood cell). Glivec is used in patients with "Philadelphia positive chromosome" (Ph +). This means that some genes of these subjects have reorganized themselves to form a special chromosome, called, precisely, "Philadelphia chromosome". Glivec is used in adults and children with newly diagnosed Ph + CML in whom bone marrow transplantation is not recommended. Glivec is also used in adults and children in the "chronic phase" of the disease, after failure of therapy with interferon alpha (another anticancer medicine), and at a later stage of the disease ("accelerated phase" and "blast crisis") ;
- acute lymphoblastic leukemia with Philadelphia chromosome positive (ALL Ph +), a type of tumor characterized by a rapid proliferation of lymphocytes (another type of white blood cells). Glivec is used in combination with other anticancer medicines in adults with newly diagnosed LAA Ph +. It is also used as a monotherapy for the treatment of Ph + ALL if the disease recurs or if the patient does not respond to treatment with other drugs;
- myelodysplastic or myeloproliferative syndromes (MD / MPD), a group of diseases in which the body produces a high amount of (one or more types) of abnormal blood cells. Glivec is used in the treatment of adult patients with MD / MPD who have reorganizations of the platelet-derived growth factor receptor gene (PDGFR);
- advanced hypereosinophilic syndrome (HES) or chronic eosinophilic leukemia (LEC), two diseases characterized by uncontrolled growth of eosinophils (another type of blood cells). Glivec is used to treat adults with HES or LEC in which a specific reorganization of two genes is observed, called FIP1L1 and PDGFRα;
- stromal tumors of the gastro-intestinal tract (GIST), a type of neoplasm (sarcoma) of the stomach and intestine characterized by the uncontrolled growth of cells in the supporting tissues of these organs; Glivec is used to treat adults with GIST who cannot be surgically removed or extended to other parts of the body, as well as to adults who are at risk of re-forming a GIST following surgical removal;
- dermatofibrosarcoma protuberans (DFSP), a type of neoplasm (sarcoma) in which cells in the under-skin tissue divide uncontrollably. Glivec is used to treat adults with non-operable DFSPs and adults in whom surgery is not recommended because sarcoma has recurred after a first treatment or has spread to other parts of the body.
The medicine can only be obtained with a prescription.
How is Glivec used?
Treatment with Glivec should be started by a doctor experienced in treating patients with blood cancer or malignant sarcomas. Glivec is taken orally during a meal, with a large glass of water to reduce the risk of stomach and bowel irritation. The dose depends on the disease being treated, the age and condition of the patient, and the response to treatment, but should not exceed 800 mg a day. For more information, see the package leaflet.
How does Glivec work?
The active substance in Glivec, imatinib, is a protein-tyrosine kinase inhibitor. That is, it blocks some specific enzymes known as tyrosine kinases. These enzymes can be found in some receptors on the surface of tumor cells, including receptors that stimulate uncontrolled cell division. By blocking these receptors, Glivec helps reduce cell division.
How has Glivec been studied?
For LMC, Glivec has been tested in 4 important studies involving 2 133 adults and in a study of 54 children. One of these studies, involving 1, 106 adult subjects, compared Glivec used as monotherapy with a combination of interferon alfa (IFN) and cytarabine (other anticancer drugs). The time frame in which patients did not experience a worsening of the disease was measured in the study.
For EVERYTHING, Glivec has been studied in three studies involving 465 adults, including one that compared Glivec with standard chemotherapy (medicines used to kill cancer cells) in 55 patients who had recently been diagnosed with cancer.
For Gist, Glivec was analyzed in two main studies. One concerned 147 patients whose GIST could not be surgically removed or in which it had extended to other parts of the body, and examined the possible reduction in tumor size. This study did not compare Glivec with other therapies. The other study compared Glivec with placebo (a dummy treatment) in 713 patients whose tumors had been surgically removed. The time frame in which patients did not experience a worsening of the disease was measured in the study.
For MD / MPD (31 patients), HES and CEL (176 patients), and DFSP (18 patients), Glivec was not compared to other therapies. These studies were conducted to determine if the white blood cell count returned to normal levels or if the number of cancer cells decreased or the size of the tumor decreased.
What benefit has Glivec shown during the studies?
Glivec was more effective than the reference drugs. In patients with CML, the tumor worsened in 16% of patients taking Glivec after five years, compared with 28% of those taking a combination of interferon alpha and cytarabine. Glivec was more effective than standard chemotherapy even in patients with ALL. Among patients with surgically removed GIST, those taking Glivec lived longer than those taking placebo without tumor reformase. In non-comparative studies conducted on patients with CML, ALL and GIST, between 26% and 96% responded to treatment.
As for the other pathologies, given that they are rare diseases, the available data are scarce; despite this, about two thirds of patients showed at least a partial response to Glivec.
What is the risk associated with Glivec?
The most common side effects of Glivec (seen in more than 1 patient in 10) are weight gain, neutropenia (low number of white blood cells fighting infection), thrombocytopenia (low platelet count number), anemia ( decrease in the number of red blood cells), headache, nausea, vomiting, diarrhea, dyspepsia (indigestion)), abdominal pain, edema (fluid retention), rash, spasms and muscle cramps, muscle and joint pain and fatigue. For the full list of all side effects reported with Glivec, see the Package Leaflet.
Glivec should not be used in people who may be hypersensitive (allergic) to imatinib or any of the other substances.
Why has Glivec been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that Glivec's benefits are greater than its risks in the treatment of CLL, ALL, MP / MPD, HES, CEL, GIST and DFSP, and recommended that it be released marketing authorization.
Glivec was originally authorized in "exceptional circumstances" because, as the diseases were rare, limited information was available at the time of approval. Since the company provided the additional information requested, the "exceptional circumstances" were eliminated on 13 April 2007.
Other information on Glivec:
On 7 November 2001, the European Commission granted a marketing authorization valid for Glivec, valid throughout the European Union, to Novartis Europharm Limited. This authorization was renewed on 7 November 2006.
The summary of the opinion of the Committee for Orphan Medicinal Products on Glivec can be found here (CML: February 14, 2001), here (GIST: November 20, 2001), here (LLA: August 26, 2005), here (DFSP: August 26, 2005), here (HES and LEC: 28 October 2005), here (MD / MPD: 23 December 2005).
For the full EPAR for Glivec, click here.
Last update of this summary: 11-2012.
