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


RESULTS
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.


CONCLUSIONS
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).
Marrari
Andrea
A
Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. sgeorge2@partners.org
Trent
Jonathan C
JC
George
Suzanne
S
D001549:Benzamides; D018572:Disease-Free Survival; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D009154:Mutation; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor