can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? - EGAPPWG-

Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan?

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group*

Disclaimer: This recommendation statement is a product of the independent EGAPP Working Group. Although the Centers for Disease Control and Prevention (CDC) provides support to the EGAPP Working Group, including staff support in the preparation of this document, recommendations made by the EGAPP Working Group should not beconstrued as official positions of the CDC or the US Department of Health and Human Services.

Summary of Recommendations: The Evaluation of Genomic Applications in Practice and Prevention (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
who are to be treated with irinotecan, with the intent of modifying the dose as a way to avoid adverse drug reactions (severe neutropenia).

Rationale: The EGAPP Working Group (EWG) found no intervention trials showing that targeted dosing of irinotecan based on UGT1A1 genotyping could reduce the rates of two specific adverse drug events, severe (Grade 3–4) neutropenia or diarrhea. Observational studies indicate a
significant association between UGT1A1 genotypes, particularly *28/*28 and *1/*28, and the occurrence of severe neutropenia. Observational studies also indicate a possible association between severe diarrhea and these UGT1A1 genotypes, but the association is not statistically significant. An additional finding was the suggestion that reducing irinotecan dose may
result in patient harms due to diminished effectiveness of treatment in highest risk individuals (*28/*28 homozygotes), and that a higher dose might be warranted among individuals at lower risk of adverse drug events (*1/*1 and *1/*28 genotypes). This review did not consider higher risk patients (e.g., having previous adverse reactions to irinotecan or additional risk factors for neutropenia). Analytic Validity: The EWG found adequate evidence to conclude that analytic sensitivity and specificity were high for...


*EGAPP Working Group: Chair: Alfred O. Berg, MD, MPH (University of Washington), Members: Katrina Armstrong, MD, MSCE (University of Pennsylvania School of Medicine); Jeffrey Botkin, MD, MPH (University of Utah); Ned Calonge, MD, MPH (Colorado Department of Public Health and Environment); James Haddow, MD (The Warren Alpert Medical School of Brown University); Maxine Hayes, MD, MPH (Washington State Department of Health); Celia Kaye, MD, PhD (University of Colorado School of Medicine); Kathryn A. Phillips, PhD (University of California, San Francisco); Margaret Piper, PhD, MPH (Blue Cross/Blue Shield Association Technology Evaluation
Center); Carolyn Sue Richards, PhD, FACMG (Oregon Health & Science University); Joan A. Scott, MS, CGC (Johns Hopkins University); Ora L. Strickland, PhD, DSc (Hon.), RN, FAAN (Emory University); Steven Teutsch, MD, MPH (Merck & Co.).
E-mail: egappinfo@egappreviews.org.
Disclosure: Steven Teutsch is an employee, option and stock holder in Merck
& Co., Inc.
Submitted for publication August 8, 2008.
Accepted for publication September 23, 2008.
DOI: 10.1097/GIM.0b013e31818efd9d


full-text ► http://www.egappreviews.org/docs/EGAPPWG-UGT1A1Rec.pdf