Response to gefitinib and erlotinib in Non-small cell lung cancer: a retrospective studyReportar como inadecuado




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BMC Cancer

, 9:333

First Online: 18 September 2009Received: 12 February 2009Accepted: 18 September 2009DOI: 10.1186-1471-2407-9-333

Cite this article as: Emery, I.F., Battelli, C., Auclair, P.L. et al. BMC Cancer 2009 9: 333. doi:10.1186-1471-2407-9-333

Abstract

BackgroundIn Non-small cell lung cancer NSCLC, an overactive epidermal growth factor receptor EGFR pathway is a component of the malignant phenotype. Two tyrosine kinase inhibitors TKIs of EGFR, gefinitib and erlotinib, have been used with variable benefit.

MethodsWe have analyzed outcome data of a population of NSCLC patients that received these TKIs to determine the benefit derived and to define the clinical and molecular parameters that correlate with response. Tumor tissue from a subgroup of these patients was analyzed by immunohistochemistry to measure the expression level of EGFR and four activated phosphorylated members of the pathway, pEGFR, pERK, pAKT, and pSTAT3.

ResultsErlotinib was slightly superior to gefitinib in all measures of response, although the differences were not statistically significant. The most robust clinical predictors of time to progression TTP were best response and rash p < 0.0001. A higher level of pEGFR was associated with longer TTP, while the total EGFR level was not associated with response. Higher levels of pAKT and pSTAT3 were also associated with longer TTP. In contrast, a higher level of pERK1-2 was associated with shorter TTP.

ConclusionThese observations suggest the hypothesis that tumor cells that have activated EGFR pathways, presumably being utilized for survival, are clinically relevant targets for pathway inhibition. An accurate molecular predictive model of TKI response should include activated members of the EGFR pathway. TKIs may be best reserved for tumors expressing pEGFR and pAKT or pSTAT, and little pERK. In the absence of molecular predictors of response, the appearance of a rash and a positive first scan are good clinical indicators of response.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-333 contains supplementary material, which is available to authorized users.

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Autor: Ivette F Emery - Chiara Battelli - Paul L Auclair - Kathleen Carrier - Daniel M Hayes

Fuente: https://link.springer.com/







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