Second line therapies for the treatment of gastrointestinal stromal tumor.
OBJECTIVE
Most gastrointestinal stromal tumors eventually acquire resistance to imatinib mesylate. This review focuses on recent progress on management of patients whose disease progresses on the standard dose of imatinib.


RESULTS
Approximately 30% of patients failing standard-dose imatinib achieve disease stabilization with high-dose imatinib, but objective responses are few and the clinical benefit usually short-lived. Patients receiving enzyme-inducing drugs may need high imatinib doses to achieve therapeutic blood concentrations. Surgical excision of a single growing metastasis leads to a median progression-free survival time of 7-11 months. Sunitinib malate is effective following imatinib failure. The median time to disease progression is approximately 6 months with sunitinib therapy versus 6 weeks with placebo following discontinuation of imatinib, but few (5%) patients achieve objective response. Patients with gastrointestinal stromal tumor with KIT exon 9 mutation may benefit more from sunitinib than those with exon 11 mutation. Sunitinib frequently causes abnormal thyroid function.


CONCLUSIONS
Sunitinib is now the approved second line therapy following imatinib failure and for patients intolerant to imatinib. The clinical benefit is only moderate, and thyroid function monitoring is required. Several investigational agents are being evaluated for imatinib-resistant gastrointestinal stromal tumor. Palliative procedures, such as hepatic arterial embolization, also require study.
Joensuu
Heikki
H
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. heikki.joensuu@hus.fi
D001549:Benzamides; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D017211:Treatment Failure
D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib