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Sutent shows promise in children with metastatic GIST resistant to Imatinib

A small pilot study from researchers at Dana-Farber Cancer Institute has shown that children with a rare digestive-tract cancer that is resistant to front-line therapy may benefit from a newer targeted therapy that has been shown effective in adults.

Researchers led by Katherine Janeway, and George Demetri, of the Ludwig Center for Cancer Research at Dana-Farber have presented results of a preliminary clinical trial in which three children, two teenagers and a pre-teen, with metastatic gastrointenstinal stromal tumor ( GIST ) resistant to Imatinib (Gleevec/ Glivec ) were treated with Sunitinib ( Sutent ).

Sutent was recently approved by the FDA for use in GIST patients as a multi-targeted "smart drug" that inhibits several growth-stimulating kinase enzymes in cancer cells. With Sunitinib therapy, the GIST lesions stabilized or decreased in size in all three pediatric patients, with one patient experiencing a complete remission of two cancerous lung nodules.
Positron emission tomography ( PET ) scanning in two patients showed significant decreases in tumor-related activity at all sites where the disease was present.
Side effects of Sunitinib were manageable in all three patients.

GIST most often occurs in people over the age of 40 and can arise anywhere in the gastrointestinal tract. Studies have estimated that there are at least 5,000 new cases a year in the United States.
Very rare in children, GIST was found to account for less than 5 percent of all cases of the disease at one major cancer center.

In most young people with GIST, the cancer cells do not have detectable mutations in the genes encoding the KIT and PDGFR-a, kinases, although these signaling proteins are uncontrollably activated. Adults with GIST whose tumors lack mutations in these genes generally do not benefit from Imatinib therapy, but show significant improvement with Sunitinib treatment.
These findings led researchers to test Sunitinib in pediatric GIST patients.

" The results of this initial trial confirm our prior observations that Sunitinib is an effective therapy for GIST cells without kinase mutations, and it is particularly important for these pediatric patients with Imatinib-resistant GIST, " says Demetri, the study's senior author.

Source: Dana-Farber Cancer Institute, 2006