Targeted Therapy for Gastrointestinal Stromal Tumor

Some drugs can target the gene changes in gastrointestinal stromal tumor (GIST) cells that have been found in recent years. These drugs work differently from standard chemotherapy (chemo) drugs. Targeted drugs are very helpful in treating GISTs, while standard chemo drugs are usually not helpful.

All of these targeted drugs are pills, taken once a day.

Imatinib (Gleevec)

This drug is used to treat most patients with GISTs at some point. It targets both the KIT and PDGFRA proteins, blocking their ability to make tumor cells grow and divide. In most GISTs, the cells have too much of one of these proteins.

Overall, most tumors shrink by at least half when treated with imatinib. Some other tumors shrink less or at least stop growing for a time. A small number of tumors are not helped by this treatment.

Imatinib can be helpful in different situations:

  • If a GIST has been completely removed by surgery, doctors typically recommend taking imatinib for at least a year afterward (unless the risk of the cancer coming back is low). This is known as adjuvant therapy. Many doctors now recommend at least 3 years of imatinib after surgery for patients who are at a higher risk of their tumors returning (based on the tumor’s size, location, and growth rate).
  • For larger tumors that may be hard to remove, imatinib may be used first to try to shrink the tumor and make surgery easier. This is known as neoadjuvant therapy. Imatinib is often given again after surgery as well.
  • Imatinib is usually the treatment of choice for advanced GISTs that have spread too far to be removed by surgery. It doesn’t seem to cure these tumors, but it can often shrink or slow their tumors’ growth for several years, helping patients live longer and feel better. If the drug stops working and the tumor starts growing again, raising the dose of imatinib may help stop the growth for some time, but higher doses can have more side effects.

Side effects can include mild stomach upset, diarrhea, muscle pain, and skin rashes. The stomach upset is lessened if the drug is taken with food. Imatinib can also make people retain fluid. Often this causes some swelling in the face (around the eyes) or in the ankles. Rarely the drug causes more severe problems, with fluid building up in the lungs or in the abdomen. It can also affect heart function in some people.

One other concern when using this drug to treat large GISTs is that these tumors often have a lot of fragile blood vessels. If imatinib causes the tumor to shrink quickly, it could lead to internal bleeding. For this reason, doctors watch patients carefully when they first start taking this drug.

Sunitinib (Sutent)

This drug can be useful in treating GIST if imatinib is no longer working or if a person can’t take imatinib because of its side effects.

Sunitinib targets the KIT and PDGFRA proteins, as well as several other proteins that imatinib does not target.

Sunitinib helps some patients, usually by slowing the growth of the tumor. It can also shrink tumors in a small number of patients. More importantly, patients getting the drug may live longer.

Common side effects of sunitinib include fatigue, diarrhea, mouth irritation, and skin and hair color changes. More serious side effects can include high blood pressure, increased risk of bleeding, swelling, heart problems, and serious liver problems.

Regorafenib (Stivarga)

Regorafenib can be used to treat GIST if imatinib and sunitinib stop working. This drug targets many proteins, including KIT and PDGFRA.

Regorafenib can slow tumor growth and even shrink some tumors. So far, though, it’s not clear if it helps people live longer.

Common side effects include diarrhea, fatigue, high blood pressure, mouth irritation, hair loss, loss of appetite, and problems with redness, pain, or even blistering of the palms of the hands and soles of the feet (called hand-foot syndrome).

Several other targeted drugs are now being studied for use against GISTs as well.

More information about these types of drugs can be found in Targeted Cancer Therapy.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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Demetri GD, Reichardt P, Kang YK, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):295-302.

National Cancer Institute. Physician Data Query (PDQ). Gastrointestinal Stromal Tumors Treatment. 2017. Accessed at on April 17, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma. V.2.2017. Accessed at on April 17, 2017.

Last Medical Review: May 17, 2017 Last Revised: May 17, 2017

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