Improved standard treatments, new research, and new drugs in development continue to advance GIST treatment.
Each year in the United States, more than 5,000 people are diagnosed with a gastrointestinal stromal tumor (GIST). GIST belongs to a class of cancers called soft-tissue sarcomas. These cancers begin in cells of soft tissue, such as muscle or fat, or in blood vessels.
When GISTs occur along the digestive tract, more than half are found in the stomach. Thirty percent occur in the small intestine; five percent, in the esophagus (food pipe); five percent, in the rectum (the end of the intestines, just above the anus); and two percent, in the colon.
Although many people with small GISTs may have nhttp://facebooknaija.com/wp-admin/post-new.phpo symptoms, larger and more aggressive tumors can cause pain or discomfort in the abdomen (the area of the body that contains the stomach, intestines, and other organs). Other symptoms include vomiting, diarrhea, blockage in the bowel, black or tarry stools, vomiting of blood, anemia, fatigue, and weight loss.
It is a hopeful time for GIST patients. Surgery and newer targeted drugs can reduce the risk of a GIST becoming life-threatening. These treatments have made it possible for many people with GIST to live far longer and with a better quality of life than ever before. In the next five years, doctors believe there will be even more rapid progress as newer targeted drugs are combined in powerful “cocktails” against GIST.
Surgery and targeted treatments are the main tools that doctors use to treat GIST. (Targeted treatments are drugs that “target” cell mechanisms that drive the growth of cancer cells. Instead of killing both healthy and unhealthy cells as chemotherapy does, targeted treatments attack mainly cancer cells.) Many of the treatment advances we’ve seen in recent years are the result of a new understanding of cancer at the level of genes and DNA, which is revolutionizing the field of GIST research. Today, there are several drugs in clinical trials for GIST, offering another important care option for people with this cancer.
Surgery is the top treatment choice for GISTs that have not spread from the place they started. The goal of surgery is to remove the whole tumor, ideally to lower the chances that the tumor will come back. Surgery also keeps tumors from blocking the digestive system or causing other problems. In some cases, to get rid of the whole tumor, part of an affected organ, such as the stomach, may have to be removed as well. Many tumors removed by surgery have a low chance of coming back, but GISTs that have certain characteristics (for example, those that are larger than three centimeters in diameter and in which the cells are growing quickly) are more likely to return. GIST at risk of coming back may also spread to other parts of the body, especially the liver.
Before surgery, doctors may treat the tumor with targeted treatments to shrink the tumor and make it easier to remove. “Down-staging” the tumor in this way is especially helpful in people whose cancer is located in sensitive areas that could be damaged by surgery. Examples of these areas include the rectum, esophagus, the area around the pancreas, or near the bile duct of the liver. Using targeted treatments before surgery can spare patients a more complicated operation and lead to a better result. These targeted treatments are described in more detail below.
Once the tumor is removed, it is examined under a microscope by a pathologist. This member of the health care team is an expert in identifying the type, cause, and progress of disease. Doctors use this information to help them judge how aggressive the cancer is and how likely it is to come back or spread. The pathologist’s report also helps doctors to decide whether drug treatment may be needed after surgery to reduce the risk of GIST returning.
Laparoscopic surgery, sometimes called “keyhole surgery,” is used in some cases, depending on the location of the GIST. With this procedure, several small cuts, or incisions, are made instead of one large cut. Through these small incisions, the surgeon can insert thin tubes that contain a light, a camera, and small surgical instruments to perform the procedure. The recovery is quicker, with less pain and fewer side effects.
Most GISTs have mutations, or changes, in one of two genes called KIT and PDGFRA. These mutations cause the cells to grow uncontrollably. Targeted drugs have been designed to slow and stop this growth by blocking the activity of certain enzymes in these mutated genes. The U.S. Food and Drug Administration (FDA) has approved two targeted treatments for GIST:
Imatinib (Gleevec) is used as a first treatment in patients for whom surgery is not an option. It may also be used before surgery to shrink a tumor that is large or has spread into nearby organs. Imatinib is also the only drug approved to decrease the risk of GIST returning after surgery, if the risk of disease return is moderate or high. This drug does not appear to cure GIST after the cancer has spread or come back. It works better at controlling the growth of some types of tumors than others. To control GIST, imatinib must be taken long-term.
Sunitinib (Sutent) is approved for the treatment of GIST if imatinib does not work or stops working. Like imatinib, sunitinib shuts down KIT and PDGFRA enzyme activity (in a somewhat different way). Sunitinib also blocks the growth of blood vessels, which likely makes it harder for GISTs to grow.
When GIST Does Not Respond to Imatinib or Sunitinib
Imatinib and sunitinib are effective treatments for GIST. However, over time, the KIT and PDGFRA genes can figure out a way to resist these targeted treatments. This “drug resistance” may not show up for some years after starting treatment. However, when it happens, new approaches must be used to control the cancer.
Doctors compare this situation to having a light switch with a lock box around it. In order to turn off the light (cancer growth), we need to use the right key to open the lock (gene mutation). The key to the lock is a targeted treatment. The problem is that over time, the lock can change. Researchers are now looking for treatments that can serve as “master keys,” able to unlock any mutations that may happen.
Another treatment challenge for GIST researchers is that about ten to fifteen percent of GISTs in adults do not have mutations and so do not respond well to imatinib or sunitinib.
They are called “wild-type” GISTs. Researchers have found that there are many different kinds of wild-type GISTs. But it turns out that wild-type GISTs are similar to some kidney cancers, so the hope is that targeted treatments used for kidney cancer may prove useful for GIST as well.
The progress that has been made in treating GIST has been possible because researchers around the world have worked together to study new drugs. Without clinical trials and the help of those patients who take part in them, we would not have the powerful, safe, and effective drugs imatinib and sunitinib. Talk to your doctor about whether a clinical trial may be right for you. In clinical trials across the country, researchers are now studying the following drugs as possible new treatments for GIST:
Regorafenib (BAY 73-4506) is somewhat similar to sorafenib (Nexavar), a drug that is used to treat kidney cancer. In large clinical trials, regorafenib has shown promising activity against GIST after the tumor develops resistance to both imatinib and sunitinib. Information from those recently completed studies is eagerly awaited.
Nilotinib (Tasigna) is used to treat certain types of leukemia (a blood cancer) in patients for whom imatinib did not work and in patients who could not take imatinib for other reasons. Nilotinib works by blocking the same enzyme activity as imatinib, though in a somewhat different way. Although nilotinib has shown some benefit, there is not enough information to suggest that nilotinib is more effective than imatinib in treating GIST. However, nilotinib may be able to control GIST if imatinib and sunitinib do not work or stop working.
Pazopanib (Votrient) is another drug that is approved for people with kidney cancer. Some early reports suggest that pazopanib might also be useful in treating GIST. Two clinical trials are under way to study this drug, one in the United States and one in Europe.
Sirolimus (Rapamune), everolimus (Afinitor), temsirolimus (Torisel), and ridaforolimus (AP23573) all block a cell mechanism called the mTOR pathway, which signals cancer cells to grow. Many of these drugs have been tested in combination with either imatinib or sunitinib in GIST and other cancers to see whether their combined use is more effective than one drug alone.
HSP90 inhibitors, such as AT13387, block a key substance inside cancer cells that contributes to the growth of GIST. AT13387 combined with imatinib is currently being studied in clinical trials.
Taking your Medication
GIST can recur when you stop taking the pills your doctor has prescribed. Many people living with GIST sometimes forget to take their prescribed medications. The most important thing you can do for yourself is to take your prescribed medications every day. Talk with your doctor about any problems you have sticking to your schedule.
CancerCare suggests these tips to help you stick to your prescribed medication treatment plan:
Get it in writing. When you start taking your pills, have your doctor provide written instructions that you can take home and review.
Fit the drug into your usual routine. Check with your doctor about the best way to take your pills, including the time of day, before a meal, or with food. It is always best to swallow your pills with water. If you are taking many pills, ask your doctor or pharmacist how best to space your pills apart. Some pills cannot be taken together, so check with your health care team to learn the best way to take your pills.
Take your prescribed pills the same time every day.
Consider using a pill sorter (available at drug stores) to sort your week’s medications. Fill it with your week’s supply of medicine.
Place reminders on your calendar to refill your prescriptions several days before they run out.
Know what to do if you miss a dose. Discuss this with your health care team. Do not take a double dose to make up for a missed one.
If you have trouble swallowing pills, ask your oncologist, nurse, or pharmacist for suggestions on what to do. Your health care team can advise you on the best method to use.
Know what to expect. Medications often have side effects. Review with your health care team expected side effects that you may experience as a result of taking your prescribed medications. If you experience any unusual or unexpected symptoms, call your doctor immediately. Do not try to treat these side effects on your own.
Do not stop taking your medication without talking to your doctor.