Gene :: Genes and Drug Dose Predict Increased Risk of Neutropenia from Irinotecan

Patients with a particular version of the UGT1A1 gene are at greater risk of neutropenia, a shortage of certain white blood cells, if they are taking medium or high doses of the anticancer drug irinotecan.

In 2005, the FDA highlighted an increased risk of neutropenia from irinotecan in these patients. However, it is unclear when DNA testing would be of highest value for managing this important anticancer drug.

Janelle Hoskins, Ph.D., of the University of North Carolina in Chapel Hill and colleagues reviewed data from nine studies on irinotecan and neutropenia risk according to which version of UGT1A1 patients had. They found that patients who received a medium or high dose of the drug had greater risk of neutropenia if they had two copies of UGT1A1*28, compared with two copies of UGT1A1*1 or one of each. At lower doses the risk was the same regardless of which version patients had.

?We recommend that the product information for irinotecan be amended to describe the association between irinotecan dose and risk of [neutropenia] among patients with a UGT1A1*28/*28 genotype,? the authors write.

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