Treating advancing GIST ... page 2

For patients who relapse following treatment with Glivec, or who do not respond, Sutent (or sunitinib) was trialled in 2004/05. It too showed a remarkable effect and was licensed in August 2006 for 'second-line' use for patients refractory on Glivec. It was approved for use in the NHS in 2009.

Mutations of c-kit

Research has revealed that mutations in c-KIT which drive the development of GIST tumours can differ between patients.  A mutation at Exon11 is the most common mutation (about 85% of cases) and patients with this form of GIST are most likely to be responsive to Glivec. A mutation at Exon9 is rarer (about 10% of patients) and research suggests that a double dose (800mg/day) has a similar effect.  A small percentage of patients have mutations at other locations in the GIST cell, or no identifiable mutations at all.  Research continues to find the best route to treat these patients. For some of these other mutations Sutent may be an appropriate first line therapy.

However, at this time, neither double dose Glivec, nor Sutent as a first-line therapy are guaranteed funding by the NHS.

Reasons for relapse

Patients who respond well to Glivec at the standard dose of 400mg/day (mostly those with an Exon11 mutation) will be closely monitored for signs of relapse. Sadly about half will have done so by 24 months, but there are many who do not show any signs of progressive disease for several years, and a percentage who will be stable or even disease free at more than five years. A few patients have gone 9 years or more (which is as long as anyone has been taking Glivec).

It is clear that resistance to Glivec builds up over time and the GIST tumour finds ways around Glivec's action.

Treatment options

The standard dose of Glivec is 400mg/day. When a patient shows signs of progressive disease the doctors will undertake a review to see which tumours are advancing and to make an assessment of whether further surgery might be possible.

If not they will consider increasing the dose of Glivec to 800mg/day - a dose which is not automatically funded by English PCTs. They may also consider whether Sutent is an option, this is funded by the NHS.

Further research

GIST is one of the most heavily researched rare cancers at present.  The success of Glivec and the understanding which researchers have gained from the trials with GIST patients has shown possible routes for the treatment of other cancers.

Tests and clinical trials continue, both to understand GIST and its response to Glivec, and to examine how Glivec might help patients with other cancers. The kind of response shown by CML and GIST patients will not be seen in another cancer but Glivec in combination with other therapies, either standard or newly developed, may well prove to be active agent.

Similarly research for new agents which would help GIST patients is also underway. A drug from Novartis called nilotinib (Tasigna) is currently being closely considered in clinical trials.

If you want to find out more the following links offer a starting point.

The NHS Guidelines for treating GIST with Glivec (imatinib)

The NHS Guidelines for treating GIST with Sutent (sunitinib)

GIST Support UK - patient advice

The Liferaft Group - patient support and patient led GIST research

GIST Support International - patient support group

Reports on Dr Brian Drucker's early research

Page reviewed December 2009