The U.S. Food and Drug Administration requires the irinotecan package labeling to indicate that patients with UGT1A1*28 are at increased risk for neutropenia and that clinicians should consider using a reduced dosage for these individuals, Stewart said. Based on this warning, we wanted to determine if children with the UGT1A1*28 gene variation were likely to suffer the same toxicity even if they received irinotecan in 10 small doses over two weeks instead of one large dose.
The St. Jude team conducted a retrospective study of 74 children who had received this low-dose treatment for any of a variety of solid tumors. A total of 27 children had both copies of the normal gene UGT1A1 with six copies of TA in the promoter region; 36 had one normal and one UGT1A1*28 gene with seven copies of TA; and nine had two copies of UGT1A1*28.
The researchers found no association between UGT1A1*28 and either diarrhea or neutropeniaeven if the patient had two copies of this gene when irinotecan was given at the reduced dose. Therefore, the researchers concluded that it was not useful to test patients to determine if they had UGT1A1*28.
This is a negative finding in the sense that the UGT1A1*28 variation does not seem to predict toxic responses in patients treated with low-dose irinotecan, said Lisa McGregor, M.D., Ph.D., assistant member of the St. Jude Department of Oncology and the reports senior author. But it should help clinicians design effective and safe irinotecan treatments for individual children.