These results suggest that polymorphic variations in the intron 1 of the egfr gene is associated with response to EGFR inhibitors and may provide an explanation as to why the development of skin toxicity is associated with a favorable outcome in patients treated with these agents.
Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients.
Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95% CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95% CI, 0.61-1.89) (p(interaction) =0.14).
Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients.
Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients.
Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04-4.99).
However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P </= .05).
The biology of responsiveness is still unclear, although there is growing evidence of an association of skin toxicity or presence of shorter EGFR intron 1 cytosine-adenine repeats with positive outcome.
In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.
Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy.
Our study revealed an influence of the EGFR-R521K genotype on skin toxicity and suggested its relation to clinical activity of cetuximab/docetaxel treatment.
Sex (p=0.005), non-smoking status (p=0.010), skin toxicity (p=0.020), EGFR gene mutations (p<0.001) and EGFR FISH positivity (p=0.016) were found to be associated with gefitinib response.
However, the other three coding XRCC1 variants did not influence the risk of ≥grade 2 acute skin toxicity for patients with breast cancer after radiotherapy.
Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058).
Although skin toxicities are the most common adverse events associated with EGFR inhibitors, the differences in efficacy and safety between pre-emptive and reactive skin treatment according to KRAS tumor status has not been reported.
A placebo-controlled phase 3 trial demonstrated that the epidermal growth factor receptor (EGFR) inhibitor erlotinib in combination with gemcitabine was especially efficient in a pancreatic ductal adenocarcinoma (PDAC) subgroup of patients developing skin toxicity.