Treatment of inoperable gastrointestinal stromal tumor (GIST) with Imatinib (Glivec, Gleevec).
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.
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.
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.


CONCLUSIONS
Imatinib is the first effective systemic therapy for advanced GIST.
Joensuu
Heikki
H
Department of Oncology, Helsinki University Central Hospital, Finland. heikki.joensuu@hus.fi
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics; D017154:Stromal Cells; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit