Treatment of inoperable gastrointestinal stromal tumor (GIST) with Imatinib (Glivec, Gleevec).
Heikki Joensuu
Abstract
Heikki Joensuu
Abstract
BACKGROUND: Imatinib (STI571 or Glivec, Novartis) is a new type of tyrosine kinase inhibitor that selectively inhibits various tyrosine kinases including ABL, BCR-ABL, KIT and PDGF receptors. IMATINIB IN CML: Earlier studies have shown that Imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), which is characterized by translocation of chromosome material from chromosome 9 to chromosome 22 with formation of the so-called Philadelphia chromosome. During this process, an abnormal fusion protein, tyrosine kinase BCR-ABL, is formed. In a phase I study it was shown that a daily dose of 300 mg Imatinib resulted in a complete hematological response in almost 98% of the patients. IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also suitable indications for treatment with Imatinib, the prerequisite being overexpression by the tumor of c-KIT (CD117). This tumor entity responds extremely poorly to polychemotherapy. Initial case reports and various study approaches appear to indicate that treatment of GIST with Imatinib is a highly promising therapeutic option in this entity. Follow-up studies with FDG-PET have shown an appreciable decrease in uptake by tumor tissue, in some cases within only a few days, which may well indicate an inhibition of intratumoral metabolism and growth. Most patients with metastatic GIST achieve durable responses with imatinib, and the disappearance of cancer-related symptoms is often rapid. CONCLUSION: Imatinib is the first effective systemic therapy for advanced GIST.
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BACKGROUND: Imatinib (STI571 or Glivec, Novartis) is a new type of tyrosine kinase inhibitor that selectively inhibits various tyrosine kinases including ABL, BCR-ABL, KIT and PDGF receptors. IMATINIB IN CML: Earlier studies have shown that Imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), which is characterized by translocation of chromosome material from chromosome 9 to chromosome 22 with formation of the so-called Philadelphia chromosome. During this process, an abnormal fusion protein, tyrosine kinase BCR-ABL, is formed. In a phase I study it was shown that a daily dose of 300 mg Imatinib resulted in a complete hematological response in almost 98% of the patients. IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also suitable indications for treatment with Imatinib, the prerequisite being overexpression by the tumor of c-KIT (CD117). This tumor entity responds extremely poorly to polychemotherapy. Initial case reports and various study approaches appear to indicate that treatment of GIST with Imatinib is a highly promising therapeutic option in this entity. Follow-up studies with FDG-PET have shown an appreciable decrease in uptake by tumor tissue, in some cases within only a few days, which may well indicate an inhibition of intratumoral metabolism and growth. Most patients with metastatic GIST achieve durable responses with imatinib, and the disappearance of cancer-related symptoms is often rapid. CONCLUSION: Imatinib is the first effective systemic therapy for advanced GIST.
Key concepts: Imatinib, GiST, Medicine, Cancer research, CD117, Tyrosine kinase, Tyrosine-kinase inhibitor, Philadelphia chromosome