Targeted Therapy for Gastrointestinal Stromal Tumor

Some drugs are able to 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 effective.

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

Imatinib (Gleevec®)

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

Overall, about 2 out of 3 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.

If a GIST has been completely removed by surgery, many doctors recommend you take imatinib for at least a year afterward to lower the risk of the cancer coming back. (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 their tumor’s size, location, and growth rate).

For larger tumors that may be hard to remove surgically, imatinib may be used first to try to shrink the tumor and make surgery more successful. (This is known as neoadjuvant therapy.) It is often given again after surgery as well.

Imatinib is also 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 patients, but it can often shrink or slow their tumors’ growth for several years, helping them 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 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 may 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 when imatinib doesn’t work or when patients can’t take imatinib because of its side effects (see previous section). 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.

The most common side effects of sunitinib are 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 is given to patients to treat GIST after imatinib and sunitinib stop working for them. It targets many proteins, including KIT and PDGFRA.

In studies, regorafenib has slowed tumor growth and even shrunk some tumors. So far, though, it’s not clear if it helps patients 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).

More information about the kinds of drugs considered targeted therapy can be found in Targeted Therapy.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: April 4, 2014 Last Revised: February 8, 2016

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