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Rudin content, MD, PhD, Sidney Kimmel Comprehensive Cancer Center buy soma drugs Mesa at Johns Hopkins, David H. Koch Cancer Research Building, Room 544, 1550 Orleans St., Baltimore, MD 21231, e-mail: at jhmi.edu Rudin To assess the determinants of pharmacogenomics and pharmacokinetics of rash and diarrhea, the two main toxicities. dose-limiting factor receptor (EGFR) tyrosine kinase erlotinib buy soma drugs Mesa PATIENTS AND METHODS: In a prospective clinical study of 80 cancer patients with non-small cell lung, head and neck cancer and ovarian cancer was performed. Detailed pharmacokinetics and toxicity of erlotinib were evaluated. Polymorphic loci in EGFR, ABCG2, CYP3A4, CYP3A5 and genotype, and their effects on the pharmacokinetics and toxicity were evaluated. Results: A novel diplotypes of two polymorphic loci in the ABCG2 promoter involving-15622C / T and buy soma drugs Mesa 1143C / T has been identified, with alleles conferring lower ABCG2 levels associated with pharmacokinetic parameters, including erlotinib higher AUC (p = 0.019) and maximum concentration (P = 0.006). The variability of rash was best explained by a logistic regression model that incorporates trough plasma concentrations of erlotinib (P = buy soma drugs Mesa 0.034) and EGFR intron 1 polymorphism (P = 0.044). Variability in diarrhea was associated with two polymorphisms in the promoter of the EGFR (P 0.01) but not with erlotinib concentration Conclusion. Although exploratory in nature, this combined pharmacogenomic and pharmacokinetic model helps buy soma drugs Mesa to define and differentiate the major determinants of the skin and gastrointestinal buy soma drugs Mesa toxicity of erlotinib. The results buy soma drugs Mesa can be useful both in designing trials targeting a particular severity of the rash and in considering changes to the dose and schedule buy soma drugs Mesa of the patients experienced dose limiting toxicities of erlotinib or similarly buy soma drugs Mesa targeted agents.

Further studies on the relationship between germline polymorphisms in EGFR and the toxicity and efficacy of EGFR inhibitors are warranted. Erlotinib is the only epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor currently approved for marketing in the United States.

The most common side effects of erlotinib include rash diarrhea.1-3 and two of these toxicities can be severe and can lead to discontinuation of treatment. A strong association, but some unexplained rashes and survival was observed in buy soma drugs Mesa patients receiving erlotinib for various epithelial cancers, including lung cancer, head and neck, ovarian and cancer3 Interestingly, the toxicity spectrum and the association between the clinical benefit and rash were observed in all classes buy soma drugs Mesa of EGFR inhibitors.

Rash and diarrhea associated with the EGFR inhibitor use buy soma drugs Mesa both show great variability. Several buy soma drugs Mesa possible explanations for this observation have been proposed, including pharmacodynamic and pharmacokinetic (PK) variability.4, 5 Identify the determinants of variability can give you a basic idea guiding the design of future clinical research in defining rational strategies for maximize benefits and minimize the clinical effects in patients treated with these agents.