Volume 1, Issue 4, 04/02/2009
How do genetic polymorphisms to UGT1A1*28 increase the risk for life-threatening neutropenia when receiving irinotecan (Camptosar®)?
It is well known that the chemotherapeutic regimen of irinotecan (CPT-11, Camptosar®) in combination with 5-f luorouracil and leucovorin is an effective treatment for one of the most common forms of cancer in the western world, metastatic colorectal carcinoma.(1) Like many chemotherapeutic agents, irinotecan is known to cause a number of adverse drug events (ADE). Of greatest concern is the development of severe myelosuppression (in particular neutropenia) that may be life-threatening. Patients at greatest risk for this are those over the age of 65, those having previously received pelvic/abdominal irradiation, patients with low performance status, and patients heterozygous (TA6/TA7) or homozygous (TA7/TA7) for UGT1A1*28 allele.(1,2) What does heterozygous and homozygous mean? Since all humans have 2 copies of a gene coding sequence (or allele), a person is heterozygous if they carry 1 copy of the normal gene and 1 copy of the mutant gene and are homozygous if they have two identical copies of the mutant gene (or gene variation).(3) It is this genetic polymorphism (or variation) or risk factor that is the focus of this newsletter issue. It is estimated that approximately 10% of the North American population is homozygous for this allele.(1) So what role does UGT1A1*28 polymorphism play in causing irinotecan-induced myelosuppression?......To read the full answer please LOGIN or SUBSCRIBE NOW.
