All You Need to Know About <i>UGT1A1</i> Genetic Testing for Patients Treated With Irinotecan: A Practitioner-Friendly Guide.

Abstract

Irinotecan is an anticancer agent widely used for the treatment of solid tumors, including colorectal and pancreatic cancers. Severe neutropenia and diarrhea are common dose-limiting toxicities of irinotecan-based therapy, and <i>UGT1A1</i> polymorphisms are one of the major risk factors of these toxicities. In 2005, the US Food and Drug Administration revised the drug label to indicate that patients with <i>UGT1A1*28</i> homozygous genotype should receive a decreased dose of irinotecan. However, <i>UGT1A1*28</i> testing is not routinely used in the clinic, and specific reasons include lack of access to concise information on this wide issue as well as mixed recommendations by regulatory and professional entities. To assist oncologists in assessing whether and when to use <i>UGT1A1</i> genetic testing in patients receiving irinotecan-based therapies, this article provided (1) essential knowledge of <i>UGT1A1</i> polymorphisms; (2) an update on the impact of <i>UGT1A1</i> polymorphisms on efficacy and toxicity of contemporary irinotecan-based regimens; (3) dosing adjustments based upon the <i>UGT1A1</i> genotypes, and (4) recommendations from currently available guidelines from the US and international scientific consortia and major oncology societies.