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Your GIST Treatment Guide

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What Are GIST Targeted Therapies? continued...

In certain circumstances, Gleevec may not be recommended after surgery. These circumstances may include KIT negative tumors (13%) or the presence of the PDGFRA gene (4%). In the latter instance, the PDGFRA gene conveys imatinib resistance, but also reduces the risk of GIST recurrence.

“There are different kinds of mutations in GIST tumor cells,” says Demetri. “About one out of five GISTs is driven primarily by something called the PDGFRA gene. This makes them resistant to Gleevec, so there’s no point to taking it. The good thing is that this mutation also makes the tumor act like a pussycat; it might be very big, but it rarely would come back. That’s why it’s important that your tumor cells undergo molecular testing, so that you don’t spend years on a treatment that won’t do anything for you.”

Gleevec is a “targeted therapy,” known as a tyrosine kinase inhibitor (TKI). These drugs interfere with the signals sent out by cancer cells, specifically those with the KIT mutation.

“Most people tolerate Gleevec very well,” says Demetri. However, as with all medications, there are side effects. The most common side effects of imatinib include:

  • Fluid retention
  • Swelling around the eyes and legs
  • Diarrhea, nausea, and vomiting
  • Muscle cramps
  • Muscle or bone pain
  • Abdominal pain
  • Fatigue
  • Excessive gas
  • Rashes

Some patients cannot tolerate imatinib and have to discontinue the drug. The most serious side effect -- severe liver dysfunction -- may result in the withdrawal therapy.

In this case, or for tumor recurrence or resistance during imatinib therapy, the drug sunitinib (Sutent) is used. This drug has a GIST control rate of more than 50% with 2-year survival rates.

“Sutent targets a different genetic signaling switch than Gleevec does, so it has different toxicities. You don’t get the swelling you see with Gleevec, but instead you get others, like mouth sores and change in taste, and most commonly high blood pressure, which doctors will need to monitor closely,” says Demetri.

The drug regorafenib (Stivarga) is used to treat patients who have tumors that cannot be surgically removed and no longer respond to other GIST treatments.  

Other agents being evaluated for GIST include sorafenib (Nexavar), dasatinib (Sprycel) and nilotinib (Tasigna).

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