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UGT1A1 Gene Affects Risk of Irinotecan-Induced Toxicity

Neutropenia risk is higher in UGT1A1*28/*28 carriers who receive medium to high doses

WEDNESDAY, Sept. 5 (HealthDay News) -- Cancer patients with a UGT1A1*28/*28 genotype who receive medium to high doses of irinotecan may have a significantly increased risk of neutropenia, according to a report published in the Sept. 5 issue of the Journal of the National Cancer Institute.

Janelle Hoskins, Ph.D., of the University of North Carolina in Chapel Hill, and colleagues conducted a meta-analysis of nine studies that included a total of 821 patients.

The researchers found that patients with a UGT1A1*28/*28 genotype had a higher risk of irinotecan-related hematologic toxicities (grade III-IV) than patients with a UGT1A1*1/*1 or UGT1A1*1/*28 genotype when receiving both medium and high doses (odds ratios, 3.22 and 27.8, respectively). They also found that patients with a UGT1A1*28/*28 genotype had a similar risk of toxicities when receiving low doses (OR, 1.80).

"We recommend that the product information for irinotecan be amended to describe the association between irinotecan dose and risk of hematologic toxicity among patients with a UGT1A1*28/*28 genotype," the authors write. "We also favor the development of consensus guidelines by national and regional bodies (e.g., the National Cancer Institute, American Society of Clinical Oncologists, European Society of Medical Oncology, or National Comprehensive Cancer Network) for optimal use of UGT1A1*28 genotype information to prescribe irinotecan doses."

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