Novel tyrosine kinase inhibitor improves survival in patients with Glivec-resistant GIST
Survival in patients with gastrointestinal stromal tumours (GIST) who had become resistant to imatinib (Glivec) was improved by treatment with a new oral, multi-targeted tyrosine kinase inhibitor, SU11248. Treatment also achieved response in late-stage kidney cancer.
In a study, 312 patients with GIST who were resistant or intolerant to
imatinib were randomised to SU11248 (25-75mg/day) or to careful observation,
and switched to active treatment if their cancer progressed. Results
showed that SU11248 more than quadrupled duration of disease control,
with a median time to tumour progression of 6.3 months compared with
1.5 months (hazard ratio 0.335; P<0.00001). It also reduced the risk
of death by approximately 51 per cent (hazard ratio 0.491; P=0.00674).
George Demetri, assistant professor of medicine, Dana Farber Cancer Institute,
Boston, Massachusetts, said: “These results substantiate the concept
that multi-targeted drugs such as SU11248, which blocks the tyrosine
kinase enzymes controlling production of several molecular signals involved
in tumour growth, can overcome resistance to other targeted drugs such
as Glivec in cancer.”
He explained that GIST was a key disease for investigating the effects
of these inhibitors because it has mutations that cause the enzymes to
become overactive. Two further studies in metastatic renal cell carcinoma
showed a response rate of 40 per cent with SU11248.
The data were presented at the American
Society of Clinical Oncology meeting in Orlando, Florida, last month. |
The
Pharmaceutical Journal
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