Treatment of GIST

1. Introduction

Once a GIST has been diagnosed by a specialist pathologist, you are best looked after by a Multi Disciplinary Team (MDT) with real expertise in treating GIST. There may be two MDTs involved in your care. The first will be the team which removed your tumour, if this has been done. This team will be specialists in the part of your body where the tumour was eg stomach, intestines, rectum. This is the Site Specific MDT. The second will be the team concerned with your on-going treatment with drugs, or just surveillance. This is the Sarcoma MDT. Many patients with GIST are still being treated in small general hospitals with little knowledge or experience of GIST. You should make sure that you are being treated by GIST specialists. Medical experts who have experience of treating large numbers of GIST patients and who have developed first hand experience of this rare cancer. 

The NICE "Improving Outcomes Guidance for People with Sarcoma", was published in March 2006. This document  recommendations this document makes, are:

"The site-specific MDT has primary responsibility to liaise with the sarcoma MDT to discuss the management of each patient. Specified care plans, taking into account currently available clinical trials, should be used. It should be made clear to patients who their key worker is.

Site-specific and sarcoma MDTs need to ensure that clear pathways exist between the two MDTs, to have common treatment pathways
and to clarify under what circumstances patient care should be transferred from one to the other.

The medical management of patients with GIST should be supervised by cancer specialists with experience in the management of patients with GIST."

It also states that,

"A sarcoma MDT is expected to manage at least 100 new patients with soft tissue sarcomas each year."

It goes on to say that the anticipated benefits of this, will be

"....that all patients have access to appropriate expertise and advice. This should lead to better coordinated and specialist care and improved outcomes in terms of both survival and local control."

In July 2019 NHS England published the First Sarcoma Service specification incorporating the National GIST Guidelines and mandated that GIST and Sarcoma patients should be managed by a specialist Sarcoma MDT (Multidisciplinary team) and/or at a hospital who is recognised as a designated member of the extended Sarcoma MDT. These teams are able to demonstrate that they have experience of managing significant volumes of GIST patients.

The full detail of the NHS England Sarcoma Service Specification can be viewed here.

One of the problems for new patients has until now been that it is not always easy to identify the specialist sarcoma MDTs. This Service specification is designed to resolve this problem. A supporting indicator of expertise is to look at where clinical trials are being carried out and whether a hospital is able to perform mutational testing of tumour tissue. Mutational analysis is increasingly important to the treatment of GIST. Hospitals we believe to be currently involved are shown below:

Hospital Clinical Trials? Mutational testing?
Beatson Cancer Institute in Glasgow
Northern Centre for Cancer Care in Newcastle
The Christie Hospital in Manchester
Weston Park Hospital in Sheffield
Queen Elizabeth Hospital Birmingham
Addenbrooke’s Hospital in Cambridge
University College Hospital in London
The Royal Marsden Hospital in London and Sutton (Surrey)
Velindre Hospital in Cardiff
Bristol Royal Infirmary
St James's University Hospital, Leeds
Oxford University Hospitals NHS Trust No Yes
Royal Liverpool and Broadgreen University Hospitals (including Clatterbridge) No Yes

There may be others, and if you know of them do please let us know. All these hospitals are well reported by our members.

There are also hospitals where members of GCUK are very confident in their medical team, and feel happy to recommend them. These will have a close relationship with one of the specialist centres listed above.

2. Surgery

Surgery to remove all the tumour, or tumours, is usually the first choice, provided this is possible. The tumour, with part of the organ it is attached to, will be removed. The aim is always to remove as much of the surrounding tissues as necessary to ensure that all the GIST cells have gone. In surgical terms this is known as an "R0 resection"

2.1 GIST in the Stomach

This will mean removing part or all of the stomach and possibly the spleen as well. The surgeons will try not to remove all the stomach unless it is absolutely necessary, because life after a total gastrectomy is much more difficult than life after a partial gastrectomy. Loss of the spleen is not a big problem: the patient just has to be careful as bacterial infections develop very fast. The patient may be put on antibiotics for life. We have two booklets available giving tips on living with a gastrectomy (partial or total). These are "Living after GI surgery for GIST" and "No Stomach?".  They can both be downloaded from our Publications page.

There is also a very good description of stomach surgery available at Follow the links for surgery for stomach cancer.

2.2 GIST in the intestines

Again, the tumour will be removed with as much of the gut as is necessary to be sure that it has all gone. Losing part of your gut is not usually much of a problem afterwards.

After a GIST has been completely removed (from the stomach or the intestines), some patients have no further problems, especially if the tumour was small, on the stomach, and only growing slowly.

2.3 GIST in the liver

GISTs do not usually affect the liver first. GISTs in the liver are almost always secondaries from the stomach or gut. Liver surgery has only been possible fairly recently. Great advances are being made in the methods used, and it is now sometimes possible to remove GISTs from the liver surgically. It is also sometimes possible to use a new technique called Radio Frequency Ablation (or RFA). This is done through a tiny hole, and is much less invasive than surgery, but is only used on small tumours.

3. Drug treatment

3.1 Treatment with Glivec®

(Click here for a summary of the NICE guidelines for the use of Glivec® for the treatment of GIST.)

Glivec is the trade name for the generic drug called imatinib mesilate, often just referred to as imatinib. When it was being developed it had the research code STI-571. All these terms are still in use! Glivec is one of a group of drugs called targeted drugs. They are designed with a very specific molecular shape to fit into a space in a specific molecule. In the case of Glivec, it fits into a tyrosine kynase molecule and stops it working.

If a GIST cannot easily be removed, either because it is too large, or it is in a difficult place, Glivec will usually be prescribed. In 85% of patients it will stop the GIST growing and in many cases the tumour will shrink. This may mean that surgery to remove it becomes possible.

Glivec does not "cure" the underlying condition. The condition sends out messages "make tumours" to the body. Glivec stops the messages getting through, so growth of the tumour is inhibited. That is why one must take Glivec for life. It's rather like wearing spectacles: your eyesight is not cured but you can continue with your life normally so long as you wear them.

Trials are taking place to see whether Glivec will help to prevent recurrence after surgical removal of the tumour. It will be years before we know the answer! (See our Clinical Trials page.)

Glivec is now licensed for the treatment of adult patients with metastatic or inoperable GISTs, and is approved by the National Institute for Clinical Excellence (NICE). Glivec is very expensive, and only has NICE approval for 400mg. Officially it can only be continued if the patient responds within 12 weeks. (For more details click on "NICE decision on GIST"). If a patient responds to Glivec they will currently be able to use the drug for three years. There are currently trials taking place to compare the benefit of five years use of Glivec compared to three years. See our Clinical Trials page.

3.1.1 Taking Glivec

Glivec is a local irritant and the reason for the instruction on the packs "Take with a large glass of water" is to minimise the irritant effect on your digestive system. So:

  • Don't let the stuff touch your digestive system in the initial concentrated form in the pills. Take it with food so that it is surrounded when inside. 
  • Glivec is very soluble in water so drink at least half a pint of water with each dose of pills. This way you can get it diluted as quickly as possible. 
  • Don't lie down or slump on the sofa for an hour after taking it. If possible sit upright or, better, walk about a bit to shake it up and encourage it to dissolve and get into your bloodstream.

For most people the side-effects of Glivec are not difficult to deal with, and certainly nothing like the serious side-effects of conventional chemotherapy. This is mainly because the drug is targeted at a particular chemical process in the body. Conventional chemotherapy acts by attacking all rapidly dividing cells in the body. Of course, cancer cells are dividing rapidly, but then so are many other types of non-cancer cells. An example of this would be the cells providing hair growth, hence the familiar loss of hair during chemotherapy.

3.1.2 Possible side-effects of Glivec

Glivec does have side-effects, most of which seem to diminish with time (or maybe one just gets used to them):

Everyone experiences some tiredness and fatigue, at least at first. This was the most common side-effect in a survey of about 200 GIST patients undertaken by the Life Raft Group. In many patients, this fatigue may still be the effect of abdominal surgery, as well as the effect of Glivec. This may help to explain why it gets better with time. In any case, what's wrong with a quick afternoon nap?

Everyone seems to experience the strange side-effect of "puffy eyelids" and some eye-watering. This is a weird effect, considering where the drug is targeted, but it does ease with time in most patients and is not exactly painful or crippling.

It is quite common to get digestive upsets of various kinds, most commonly wind ("gas" in the US) and the associated discomfort. Some patients are affected by diarrhoea. These digestive upsets are most troublesome in patients who have had part (or all) of their stomach removed because of the position of the original GIST. Glivec does cause digestive upsets and some discomfort (hardly pain), which can be mitigated by taking the drug with food and a large glass of water.

There are a variety of rather surprising effects associated with skin and body hair. Some patients experience rashes and skin roughening which is helped by skin creams and anti-itch prescriptions. Body hair seems to turn brittle and be easily rubbed off by clothing. Quite a few (mainly male) patients have reported that their head hair has darkened from grey and there are a few cases of hair re-growth on bald patches(!).

There is a feeling that Glivec reduces high blood pressure, so if medication is being taken for hypertension, one's GP must be aware of this and not lower the blood pressure too much by the combination of drugs.

A few reports indicate that Glivec may be effective in reducing blood cholesterol levels, so again your GP should check this.

In August 2006 there was a report that Glivec may affect the heart in a very small number of patients. However the risks appear to be small, and for a patient with inoperable GIST there really is no choice. (We do not currently know whether there are any similar side-effects with Sutent.)

Another side effect, which is rare but potentially serious, is accumulation of fluid in the body - particularly in the abdominal cavity. This is called Ascites. It seems to happen occasionally after liver surgery. It can usually be treated with diuretics, but sometimes the fluid has to be drained.

The majority of patients seem to manage the side-effects very well. Most are able to return to their normal lives, and only a few have to take specific measures to cope with the side-effects. A very few need to stop taking Glivec, or reduce the dose.

Unfortunately, some patients have GISTs which do not respond to Glivec. We now strongly suspect that this is because GIST tumours don't all have the same genetic mutations, and some respond to Glivec better than others. Other patients have tumours which stop responding to Glivec after some time, and in many cases this appears to be because of a new mutation or mutations.

At a London Patient information meeting a straw poll was conducted, in which patients were asked to list the side effects they had experienced and the frequency. The sample size was very small (19) but the results we nevertheless interesting. Click here to see the results of this poll. A similar poll was conducted for Sutent, but as the number of patients was only 5 we felt this is too small a sample to have any worthwhile meaning.

3.2 Treatment with Sutent

Sutent is the trade name for the generic drug called sunitinib, marketed by Pfizer. Both these terms are used. Sutent is a tyrosine kinase inhibitor working through multiple targets to deprive tumour cells of the blood and nutrients needed to grow.

Patients whose tumours become resistant to Glivec, or who cannot tolerate the drug, can be treated with Sutent. Sutent has been proved to be a valuable drug for GIST patients, increasing the average overall survival. There is evidence that patients who have Exon 9 mutatons, or Wild-type GIST tend to respond best to Sutent.

Possible side effects of Sutent

In most patients the side-effects of Sutent are more difficult to tolerate than those of Glivec. Some patients have to change the way they take the drug, or take a lower dose, after discussion with their oncologist.

The most commonly reported side-effects include "hand-foot syndrome" (where hands and feet become very sore), diarrhoea, skin discoloration, mouth irritation, weakness, and altered taste. Some patients also experience fatigue, high blood pressure, bleeding, swelling, and taste disturbance. Hypo-thyroidism was also observed.

Pfizer has produced an information booklet for patients taking Sutent. This gives guidance for managing side-effects, and should be given to every patient by their oncologist before they start taking the drug.

3.3 Treatment with Regorafenib (Stivarga)

This drug has now been approved for GIST in the European Union and is available for oncologists to prescribe after patients have progressed or are intolerant to imatinib and/or sunitinib. Regorafenib is the standard third line treatment for GIST patients in England, Scotland and Wales. If you live in Northern Ireland your doctor can apply to your local Health and Social Care (HSC) Trusts through the Individual Funding Requests (IFR) process.

4. Other Drugs

Other drugs are being developed, and some are now being tested in clinical trials (see Clinical Trials page).