UGT1A1*28 polymorphism in advanced colorectal cancer: The story is not yet ended.

Abstract

516 Background: UGT1A1*28 polymorphism is associated with neutropenia and diarrhea in previous reports, this study tried to investigate correlation with other toxicities like vomiting. Methods: This is a prospective case control study including all eligible cases of advanced colorectal cancer. The genotypes of UGT1A1*28 was assessed in the peripheral blood and/or in tissues by PCR. Patients were divided into two groups, group 1—patients with no mutation, group 2—patients with homo or hetero mutation. All patients received standard IFL regimen. Primary endpoints were (1) comparison between the 2 groups as regard vomiting (2) assessement of the incidence of UGT1A1*28 polymorphism. Secondary endpoints were comparison between the 2 groups as regard: neutropenia, diarrhea, treatment delay, progressive diseases (PD), progression free survival (PFS), and overall survival (OS). Results: 46 cases of advanced colorectal cancer presenting to National Cancer Institute, Cairo University, aged between 19 and 71 years with a median age of 45 years were included and followed up during the period from September 2010 to January 2013 with a median follow up of 9 months. UGT1A1*28 polymorphism was present in 20 patients (43%) of them 15% are homozygous. Grade (2-4) vomiting was found in 8.3 % of group 1 versus 52.5 % of group 2. (p = 0.01). Grade (2-4) neutropenia were found in 20.8 % of group 1 versus 64.7 % of group2. (p = 0.03). Grade (2-4) diarrhea was found in 37.5 % of patients of group 1 and 27.5% of patients with group 2. (p = 0.75). Treatment delay occurred in 29.16 % of group 1 versus 72.4 % of group 2. (p = 0.02). 25% of group 1 showed PD versus 25 % of group 2. (p = 0.8). 1 year PFS was 19% in group 1 versus 23 % in group 2. (p = 0.8) while there was a trend towards better OS in group 1 (47 % versus % 35). (p = 0.07). Conclusions: UGT1A1*28 polymorphism is present frequently (43%) in a Caucasian population and is associated with more vomiting, neutropenia and treatment delay.