May 22, 2010

Personalized cancer therapy for gastrointestinal stromal tumor: synergizing tumor genotyping with imatinib plasma levels

Current Opinion in Oncology
Andrea MarrariSuzanne George

Abstract

Imatinib has exceptional activity in controlling gastrointestinal stromal tumor (GIST) due to inhibition of the constitutively active conformation of KIT and platelet-derived growth factor-alpha (PDGFRA), which is commonly seen in this tumor. This review explores the current available data on the correlation between imatinib plasma levels, response to treatment, and the mutational status of KIT and PDGFRA. A recent retrospective analysis demonstrated a relationship between imatinib plasma levels and progression-free survival in patients with advanced GIST. Plasma imatinib levels were notably unrelated to the daily administered dose of imatinib in this small series. Prior phase III trials have demonstrated that dose escalation of imatinib may lead to increased disease control in a subset of patients with advanced GIST who progress on standard dose imatinib. Moreover, patients with GIST carrying an exon 9 mutation may benefit from higher doses of imatinib. Current available data suggest a possible correlation between imatinib plasma level and progression-free survival in patients with advanced GIST. A prospective trial is underway to evaluate whether modification of imatinib dose to achieve a target imatinib plasma level will imp...Continue Reading

  • References34
  • Citations10

References

  • References34
  • Citations10

Citations

Mentioned in this Paper

Paraganglioma AND Gastric Stromal Sarcoma
Protein Kinase Inhibitors
Exons
Piperazines
Gastrointestinal Stromal Tumors
Imatinib mesylate
Platelet-derived Growth Factor Receptor Binding Activity
Platelet-Derived Growth Factor Receptor
Imatinib
Metabolic Inhibition

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