Prospective pharmacogenetic analysis in advanced colorectal cancer (CRC) patients receiving first-line cetuximab-UFT-irinotecan therapy: Importance of gene polymorphisms related to antibody-dependent cellular cytotoxicity (ADCC)

4069 Background: Our purpose was to test the predictive value of germinal gene polymorphisms potentially linked to cetuximab, fluoropyrimidine and irinotecan pharmacodynamics on toxicity, clinical response, time to progression (TTP) and overall survival (OS). Methods: 52 patients with advanced CRC were enrolled in an ancillary pharmacogenetic study of the phase II CETUFTIRI trial (33 men, 19 women, mean age 63, range 36–84, PS 0–1). Treatment consisted in cetuximab (day 1-day 8-day 15, 250 mg/m2/week following a 400 mg/m2 loading dose) associated with irinotecan (day 1, 250 mg/m2) and UFT-folinic acid (day 1 to day 14, 250 mg/m2/day UFT, 90 mg/day folinic acid). Median number of administered cycles was 7 (range 1–8). The following gene polymorphisms were analyzed on blood genomic DNA: EGFR (CA repeats in intron 1, - 216G>T, -191C>A), EGF (61A>G), FCGR2A (131Arg>His), FCGR3A (158Phe>Val), UGT1A1 (TA repeats), TYMS (28 bp repeats including the G>C mutation on the 3R allele, 6 bp deletion in 3’ UTR), MTHFR (...