Gastrointestinal stromal tumor medical therapy
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Gastrointestinal stromal tumor Microchapters |
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Differentiating Gastrointestinal stromal tumor from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]
Overview
Medical Therapy
Treatment Option Overview for GIST
- Surgical Therapy
- Chemotherapy
- Tyrosine Kinase Inhibitor Therapy
Chemotherapy
Before the advent of molecularly targeted therapy with TKI, efforts to treat GIST with conventional cytotoxic chemotherapy were essentially futile. The extreme resistance of GIST to chemotherapy may be caused, in part, by the increased expression of P-glycoprotein, the product of the MDR-1 (multidrug resistance-1) gene, and MRP1 (multidrug resistance protein-1), which are cellular efflux pumps that may prevent chemotherapeutic agents from reaching therapeutic intracellular concentrations in GIST. There is universal agreement that standard chemotherapy has no role in the primary therapy of GIST.
Tyrosine Kinase Inhibitor Therapy
TKIs have revolutionized the management of GIST. The TKI imatinib mesylate is used as the first-line treatment for unresectable, metastatic, or recurrent GIST. Although complete responses are rare, a large majority of patients with metastatic or inoperable GIST have either a partial response or disease stabilization after starting imatinib. Median survival rates have gone from less than 2 years to more than 5 years since the advent of imatinib therapy.
Therapy with neoadjuvant imatinib to reduce the tumor volume may be used for patients with very large primary GIST that cannot be removed without the risk of unacceptable morbidity. Additional therapy with adjuvant imatinib is being studied to determine whether imatinib reduces recurrence, which is common after resection of primary GIST.
Because disease progression has been reported to follow the cessation of imatinib therapy, patients with unresectable or metastatic disease are often treated with a TKI indefinitely, as long as the disease does not progress and patient tolerance permits.
- Most small GISTs (<5 and especially <2 cm) with a low rate of mitosis (<5 dividing cells per 50 high-power fields) are benign and,after surgery, do not require adjuvant therapy.
- Larger GISTs (>5 cm), and especially when the cell division rate is high (>6 mitoses/50 HPF), may disseminate and/or recur.
- Until recently, GISTs were notorious for being resistant to chemotherapy, with a success rate of <5%. Recently, the c-kit tyrosine kinase inhibitor imatinib, a drug initially marketed for chronic myelogenous leukemia, was found to be useful in treating GISTs, leading to a 40-70% response rate in metastatic or inoperable cases.
- Patients who become refractory on imatinib may respond to the multiple tyrosine kinase inhibitor sunitinib (marketed as Sutent).