CP-225 UGT1A1*28 polymorphism and irinotecan effectiveness

Background UGT1A*28 polymorphisms have been associated with an increase in SN-38, the active metabolite of irinotecan. Thus some authors also related the presence of this mutated allele with an increase in the effectiveness of irinotecan treatment. Purpose To evaluate the influence of the UGT1A1*28 polymorphism on the effectiveness of irinotecan. Material and methods This was a prospective, observational, 4 year single centre study (November 2012–May 2016). All adult colorectal cancer patients treated with the FOLFIRI protocol (irinotecan 180 mg/m 2 /fluorouracil 400 mg/m 2 /fluorouracil 2400 mg/m 2 /leucovorin 200–400 mg/m 2 ) were included. Inclusion criteria were: ECOG 0–1, haemoglobin > 10 g/dL, leucocytes >3000/mm 3 and platelets >100 000/mm 3 ). Effectiveness was evaluated as progression free survival (PFS) and overall survival (OS). The rs8175347 UGT1A1 polymorphism was established by analysing the genomic DNA of a peripheral blood sample. Genetic characterisation was carried out using LightClycler 480 platform and specific allele HybProbe fluorescent probes. The study was approved by the hospital’s ethical committee (CEIC) and classified as EPA-SP by the Spanish Agency for Drugs and Health Products (AEMPS) with GNC-QUI-2013-01 code. Patients were requested to sign an informed consent form prior to inclusion. Results The study included 34 patients, average age 60 (27–81) years, of which 77.7% were men. 90.6% of patients were treated with anti-VEGFR or anti-VEGFA, and irinotecan was prescribed as secondline treatment. 44.4% of patients showed UGT1A1 wild-type (WT) alleles, while 41.2% and 14.7% had heterozygous and mutated homozygous alleles, respectively. After 4 years of follow-up, median PFS and OS were 7.0 and 23.0 months for patients with any mutated allele in the UGT1A1 gene, while for patients with the WT genotype, values were 8.0 (p=0.4590) and 15.0 (p=0.6128) months, respectively. Moreover, median PFS and OS were 4.0 (p=0.648) and 44.0 (p=0.1628) months for patients with the *28/*28 genotype and 7.0 (p=0.650) and 23.0 months (p=0.8354) for heterozygous patients. Conclusion Our results show that the rs8175347 polymorphism in UGT1A1 does not influence the effectiveness of irinotecan. Prospective randomised studies with a large number of patients are required to establish if this polymorphism influences the effectiveness of irinotecan therapy. No conflict of interest