GIST, or gastrointestinal stromal tumor, is a relatively rare cancer of the digestive (gastrointestinal, or GI) tract. GISTs can be found anywhere in the GI tract, including the esophagus, stomach, small intestine, large intestine (colon and rectum), and anus. However, GISTs occur most often in the stomach (60%) or small intestine (25%).^1,2,3

GIST arises from an abnormal change in the specialized cells that control the movement of food and liquid through your digestive system. A protein called KIT normally sends signals that start and stop the growth and reproduction of these cells. A mutation in the KIT gene causes this signal to be "switched on" all the time, causing the special digestive cells to grow and reproduce continuously and eventually become a cancerous tumor.^4,5

Most people diagnosed with GIST are older than 50 years, but these tumors can occur in people of any age. They are slightly more common in men than in women. Although GIST has been diagnosed in members of the same family, this is uncommon.¹

GISTs may not cause any symptoms unless they are in a certain location or grow to a certain size. When there are symptoms, these are the most common^1,4,5,6:

• Abdominal (belly) discomfort or pain
• Nausea, vomiting
• Feeling full after eating a small amount of food
• Loss of appetite
• Weight loss
• Problems swallowing (for tumors in the esophagus)
• Bleeding into the intestinal tract

GISTs are sometimes found by chance, especially when they do not cause symptoms. In these cases, the tumor may be found during an exam for another problem, such as during a colonoscopy for colon cancer.

When symptoms are present, doctors may initially investigate the cause or further evaluate suspicious findings by using any of the following tests^1,3,5:

• CT (computed tomography) scan
• PET (positron emission tomography) scan
• MRI (magnetic resonance imaging)
• Endoscopy
• Endoscopic ultrasound

If a tumor is found, specialized tests can be performed to determine if it is a GIST. These include testing the tumor tissue with a stain for the abnormal KIT protein. About 95% of GISTs have the abnormal KIT protein and are designated "KIT positive." A small percentage of GISTs are KIT negative. There are mutational tests for determining the specific gene change (mutation) causing the GIST.^5,7

• Resectable. This means that the tumor can be surgically removed²
• Unresectable. This means that because of the tumor's size and/or location, removing it would be too risky as that could severely damage surrounding organs or function^2,4
• A local recurrence. When a GIST has been surgically removed and then recurs in the same location²
• Metastatic. When cells from the tumor have spread to other parts of the body and new GISTs have begun to grow in those other sites^2,8

Surgery is the initial treatment for resectable GISTs. However, even if the tumor is successfully removed, there is a risk of recurrence. Some microscopic cancerous cells could remain and start to grow in the original tumor site or elsewhere. That is why postsurgical treatment options should be considered. These may include adjuvant therapy with GLIVEC, an oral drug that suppresses KIT activation, in addition to regular monitoring for tumor recurrence.^2,9

For unresectable or metastatic KIT+ GISTs, the first-line treatment is GLIVEC oral therapy. Chemotherapy and radiation have not proven effective in GIST. Your doctor will also want you to have regular scans to monitor the status of your disease.^1,9

No one can be certain if your tumor will or will not come back. However, a medical oncologist—a doctor that specializes in cancer—should work with your surgeon and other doctors in determining your postsurgical care. The oncologist will evaluate your individual risk of tumor recurrence based on several prognostic factors, which include:

• Tumor size
• Tumor location
• Mitotic rate or mitotic index (rate of tumor growth)

In addition, mutational status, tumor rupture, and your medical history may play a role in your risk of recurrence.

The condition of the GIST—its size, original location in the GI tract, and whether it ruptured or invaded the mucus-producing cell layer—affects the chances of the tumor recurring. The mitotic rate or index tells how aggressive the tumor had been. Other personal factors, such as coexisting medical conditions and age, will also be taken into account as they may affect your risk and what treatment may be appropriate.^5,7,10,11,12

GLIVEC is the only drug approved for the treatment of resected KIT+ GIST as adjuvant treatment after resection of the primary tumor and for the initial treatment of unresectable or metastatic malignant KIT+ GIST (advanced disease). Taken daily as a pill, GLIVEC works by specifically targeting the KIT protein and blocking the signal that tells the cancer cells to grow and reproduce.^9,13

In a clinical trial of over 700 patients with resected KIT+ GIST, 98% of patients taking GLIVEC were free from tumor recurrence after 1 year of treatment. GLIVEC reduced the risk of tumor recurrence by 88% compared with patients taking a sugar pill.¹⁴

In 2 clinical trials of over 1600 patients with advanced disease (unresectable or metastatic KIT+ GIST), more than 80% of the patients taking GLIVEC showed no disease progression (worsening) at 2 years.¹⁵

In another trial with a 5-year follow-up of over 140 patients with advanced KIT+ GIST, 84% of patients taking GLIVEC had disease control.¹⁶

In either case, GLIVEC may still be the appropriate treatment choice.

If your tumor recurs after surgery, whether or not you were taking GLIVEC, you are now considered to have advanced disease. If you were not taking GLIVEC at the time of recurrence, starting or resuming therapy at the 400-mg dose may be appropriate. If you were taking GLIVEC at the time of recurrence, your doctor may increase the dose.⁵

If you already had advanced disease and were taking GLIVEC when your disease worsened, an increase in the GLIVEC dose to 800 mg should be considered. In 2 studies of metastatic patients, about one-third of patients who progressed on 400 mg/day achieved partial tumor shrinkage or stabilization when the dose was increased to 800 mg/day. And about half of the patients had not experienced disease worsening after 2 years on the higher dose of GLIVEC.^5,9,15,17

If GLIVEC is no longer effective for you, a second-line drug may be tried.⁵

Most people will have some side effects from GLIVEC, but many are mild to moderate. Common side effects may include headache, gastrointestinal disturbances (eg, stomach upset, diarrhea), muscle pain, skin reactions (eg, rash), fatigue, and weight increase.⁹

GLIVEC may also cause retention of fluid, called edema. This is often some swelling in the face (around the eyes) or in the ankles. Less commonly, the drug may cause more severe problems, with fluid building up in the lungs and in the abdominal cavity. It may also cause blood disorders, infections, and lung and heart problems in some people.^1,9

Some side effects may be relieved with supportive care (eg, allergy medications, taking the medication with food), whereas other more serious ones may require dose adjustment or discontinuation of the drug. Talk to your doctor if you are feeling unwell or have any symptoms. They could be related to the drug treatment, postsurgical factors, or the disease worsening.^9,18

The recommended dose is 400 mg/day. GLIVEC is available as pills taken by mouth daily. You should take GLIVEC with food and a large glass of water to reduce possible stomach upset. Follow your doctor's instructions and discuss any problems you may be having.⁹

The adjuvant therapy used to treat KIT+ GIST consists of one pill (400 mg) taken daily and is well tolerated, so the impact on your life may be minimal. Though side effects vary from patient to patient, mild nausea, edema, and fatigue are the most commonly reported. However, these side effects are manageable.⁹

It is important to check with your doctor about all of the medications you are or will be taking. That includes nonprescription medicines and supplements, such as vitamins or herbal products, as well as prescribed medications. Some of these substances may affect the amount of GLIVEC in the blood or interfere with its processing. Some substances that may interact with GLIVEC include paracetamol, warfarin, St. John's wort, and some anticonvulsants. These interactions may reduce the effectiveness of GLIVEC or cause side effects.⁹

Women taking GLIVEC should take pregnancy-prevention measures. If a woman does become pregnant, she should notify her doctor right away. There is evidence from animal studies to suggest that (as with many other cancer drugs) taking GLIVEC during pregnancy may be harmful to the unborn baby.⁹

In addition, women taking GLIVEC should not breast-feed. There is limited information on the distribution of GLIVEC in human milk, and the effect of exposure in infants is unknown.⁹