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The results are presented in Table 5 for the eruption and Table 6 of diarrhea. Due to small numbers, multivariate analysis of diarrhea grade ≥ 2 was not performed. Higher levels of C min were associated withincreased buy soma CC WALLACE 2403 Roseville risk of rash of grade ≥ 2, the likely increase in eruption about 1.8 times for every 1 mg / dL increase in the level of depression. A significant effect was detected EGFR intron 1 (CA) n repeat (≥ grade 2 rash) which is associated with allele length S / L buy soma CC WALLACE 2403 Roseville with an increased risk of toxicity from s / s (p = 0.buy soma CC WALLACE 2403 Roseville 044). There was also a marginal association (P = 0.070) between the CYP3A4 and rashes on the skin with a reduced risk of G / G compared to A / A. The ABCG2 1143 C / T polymorphism is associated with a slightly lower risk destout rash grade (p = 0.086), and G-16702 / A polymorphism also confers a lower risk of any grade (p = 0.buy soma CC WALLACE 2403 Roseville 048) or high grade (p = 0.050) eruption. No statistically significant association was found between Cmin and diarrhea, only a marginal association (P = 0.10) for control of EGFR 497 G / A.

Patients with genotype G / G CYP3A5estaban higher risk of diarrhea of ​​any grade (p = 0.070) and 15 622 patients with C / T polymorphism (P = 0.057). This prospective study was conducted to assess the clinical impact of diarrhea and rash on the number of genetic polymorphisms that we and others have identified the genes encoding the target of erlotinib, as well as genes related to membrane transport and metabolism.7 8, 13,17,18,33,41 Our results indicate that the determinants of erlotinib toxicity may include the skin with the plasma concentration and buy soma CC WALLACE 2403 Roseville variability of EGFR intron polymorphism ( P = 0.034 and P = 0.044, respectively, in a multivariate model). However, diarrhea was correlated with the buy soma CC WALLACE 2403 Roseville two linked polymorphisms in the promoter of the EGFR (P 0.01) but buy soma CC WALLACE 2403 Roseville not with the concentration of erlotinib. We emphasize the fact that many polymorphic loci were tested candidate and multiple analysis of each polymorphism were performed.

The multivariate tests could lead to the detection of false associations, and therefore our results are in need of confirmation in independent data sets. Erlotinib is a substrate of CYP3A4 metabolic enzymes and Phase II CYP3A5.18 However, CYP3A4 and CYP3A5 polymorphisms determine the levels of expression and enzyme activity showed that the marginal associations with either erlotinib pharmacokinetics or toxicity observed.