Should UGT1A1 Genotyping Be Used to Predict Response to Irinotecan Chemotherapy?
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Irinotecan is a drug that is often used in combination with other chemotherapy agents to treat colorectal cancer that has spread to other parts of the body (metastatic). Certain changes in a gene known as UGT1A1 have been found to affect how quickly a person’s body metabolizes (changes) irinotecan from its active to inactive form. This could impact how much of the drug should be used (dosing), and the type and severity of side effects a person might experience.
Patients metabolize (or process) drugs differently because of a variety of factors. Variations in genes may be one reason why some people metabolize certain drugs well and other people do not. The EGAPP™ Working Group examined the scientific evidence to see whether UGT1A1 genotyping is valid and useful for guiding irinotecan dosing in the management of patients with metastatic colorectal cancer to improve effectiveness and reduce side effects.
EGAPP™ Recommendation Statement
“The EGAPP™ Working Group found that the evidence is currently insufficient to recommend for or against the routine use of UGT1A1 genotyping in patients with metastatic colorectal cancer (CRC) who are to be treated with irinotecan, with the intent of modifying the dose as a way to avoid adverse drug reactions (severe neutropenia).”
Summary of Findings on UGT1A1 Genotyping to Predict Response to Irinotecan
In 2009, the independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group evaluated the use of UGT1A1 genotyping to determine the best dose of irinotecan to prevent side effects when treating patients with metastatic colorectal cancer. The Working Group determined that there was not enough evidence to conclude whether UGT1A1 genotyping should be used for this purpose. The balance of benefits and harms of UGT1A1 genotyping to guide irinotecan use could not be determined from the available evidence.
The EGAPP recommendation statement was based on the following key points from the evidence review:
- UGT1A1 genotyping results appear accurate for the common variants.
- Observational studies identified associations between UGT1A1 genotype results and the occurrence of certain side effects, as well as a potential impact on treatment effectiveness.
- The EGAPP Working Group (EWG) found no evidence that demonstrated that targeted dosing of irinotecan based on UGT1A1 genotyping leads to improved patient outcomes.
- Even if targeted dosing were shown to be highly effective, it is not clear that benefits (reduced side effects) would outweigh harms (unresponsive tumors).
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