UGT1A1*28 Polymorphism Related Toxicities are more Frequent in Chemotherapy Naïve Patients

Irinotecan( CPT-11 ) is an important chemotherapy for the treatment of colorectal cancers. The main drawback is its toxicity which includes Neutropenia and Diarrhea.  Some studies confirms the correlation between increasing the incidence of Neutropenia and Diarrhea in patients with UGT1A1*28 polymorphism and other studies could not conclude it. So, other factors may incorporate to act with the presence of the polymorphism to increase CPT-11 toxicity. In this study, we try to find these factors. Patients were divided into 2 groups according to the presence or absence of previous chemotherapy treatment. All patients received standard IFL regimen. Primary endpoint was: comparison between the 2 groups as regard to toxicities. Secondary endpoint was assessment of the incidence of UGT1A1*28 polymorphism. UGT1A1*28 polymorphism was present in 20 patients (43%) of them 15% are homozygous. Twenty three patients were chemotherapy naive in group (1) and 20 patients in group (2) had received previous chemotherapy. Grade (II-IV) neutropenia were found in 52 % of group 1 versus 20 % of group 2 (P=0.1). Grade (II-IV) diarrhea was found in 52 % of patients of group 1 and 15% of patients with group 2 (P=0.05).Treatment delay occurred in 29.16 % of group 1 versus 72.4 % of group 2. (P=0.1). The study concluded that UGT1A1*28 polymorphism is present frequently (43%) in a Caucasian population and is associated with more incidence of toxicity in chemotherapy naïve patients.