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

Andrea Marrari, Jonathan C. Trent, Suzanne George

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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 impact patient outcome when compared with standard imatinib dosing (www.clinicaltrials.gov, NCT01031628).

Original languageEnglish (US)
Pages (from-to)336-341
Number of pages6
JournalCurrent opinion in oncology
Volume22
Issue number4
DOIs
StatePublished - Jul 1 2010

Keywords

  • gastrointestinal stromal tumor
  • imatinib plasma levels
  • tumor genotyping

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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