Article date: May 2012
By: Marie‐Christine Etienne‐Grimaldi, Jaafar Bennouna, Jean‐Louis Formento, Jean‐Yves Douillard, Mireille Francoual, Isabelle Hennebelle, Etienne Chatelut, Eric Francois, Roger Faroux, Chaza El Hannani, Jacques‐Henri Jacob, Gérard Milano, in Volume 73, Issue 5, pages 776-785
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
METHODS
Fifty‐two patients with advanced colorectal cancer were enrolled in an ancillary pharmacogenetic study of the phase II CETUFTIRI trial. Treatment consisted of 21 day cycles of cetuximab (day 1–day 8–day 15, 250 mg m−2 week−1 following a 400 mg m−2 initial dose) together with irinotecan (day 1, 250 mg m−2) and UFT–folinic acid (days 1–14, 250 mg m−2 day−1 UFT, 90 mg day−1 folinic acid). Analysed gene polymorphisms (blood DNA) were as follows: EGFR (CA repeats in intron 1, −216G>T, −191C>A), EGF (61A>G), FCGR2A (131Arg>His), FCGR3A (158Phe>Val), UDP‐glycosyltransferase1‐polypeptide A1 (TA repeats), TYMS (28 bp repeats, including the G>C mutation on the 3R allele, 6 bp deletion in 3′ UTR) and MTHFR (677C>T, 1298A>C).
RESULTS
Maximum toxicity grade was linked to EGFR−191C>A polymorphism, with 71.1% grade 3–4 toxicity in CC patients vs. 28.6% in other patients (P= 0.010). A tendency to a better response was observed in patients bearing the TYMS 3RG allele (P= 0.029) and those bearing the FCGR3A 158Val genotype (P= 0.020). The greater the score of favourable TYMS and FCGR3A genotypes, the better the response rate (P= 0.009) and the longer the overall survival (P= 0.007). In multivariate analysis, the score of favourable genotypes was a stronger survival predictor than the performance status.
CONCLUSIONS
Present data suggest the importance of FCGR3A 158Phe>Val and TYMS 5′ UTR polymorphisms in responsiveness and survival of patients receiving cetuximab–fluoropyrimidine‐based therapy.
DOI: 10.1111/j.1365-2125.2011.04141.x
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