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St. Jude shows gene test not needed if cancer drug given in low doses

Investigators at St. Jude Children's Research Hospital have shown that when the cancer drug irinotecan is given in low doses for multiple days, it eliminates the need to delay treatment to perform costly genetic testing that determines if the patient is at risk for serious treatment side effects, such as neutropenia. Neutropenia is an abnormal reduction in the numbers of immune cells, called neutrophils; the disorder leaves individuals more vulnerable to infections.

The finding means that clinicians can begin treatment sooner and eliminate the cost of this specialized test, which determines if the child carries a variation in the gene UGT1A1 that is linked to this side effect of neutropenia. By giving the drug in small doses for two weeks instead of the standard single large dose once a month, children can begin treatment with irinotecan immediately. Irinotecan is used to treat childhood solid tumors such as neuroblastoma, sarcomas and kidney tumors.

A report on this study is in the June 20 issue of the Journal of Clinical Oncology.

UGT1A1 makes an enzyme that modifies the activated form of irinotecan, a molecule called SN-38, so the body can easily remove it. Variations of this enzyme, especially one called UGT1A1*28, do not work as well and allow SN-38 to remain in the body at high levels for an extended period of time, causing side effects.

Like many genes, UGT1A1 has a series of DNA building blocks called thymidine and adenine (TA) repeating several times just in front of the gene itself. This area, called the promoter region, acts as an on switch that triggers the reading of the gene. The normal UGT1A1 has six copies of TA in front of it, while UGT1A1*28 has seven.

Previous studies had shown that when adults who carry two copies of the UGT1A1*28 gene variation received a single high dose of irinotecan, they suffered severe diarrhea or neutropenia, said Clinton Stewart, Pharm.D., associate member of the St.
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
19-Jun-2007


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