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DETERMINATION OF PROGNOSTIC AND PREDICTIVE VALUES OF CLINICAL AND HISTOPATHOLOGIC FEATURES, AND EXPRESSION OF ERCC1 AND BETAIII TUBULIN IN PATIENTS DIAGNOSED WITH ADVANCED NON-SMALL CELL LUNG CANCER TREATED WITH CISPLATIN-VINORELBINE

Grant number: 10/15761-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2010
Effective date (End): November 30, 2011
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Gilberto de Castro Junior
Grantee:Carolina Ribeiro Victor
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Lung cancer is the leading cause of death by neoplasm in Western countries. Non-small cell lung cancer (NSCLC), the most common histology of lung cancer, is present in about 50% of new cases in our midst as metastatic disease, incurable. Systemic treatment with chemotherapy based on platinum derivatives, still offers disappointing results: the response rate around 30%, with progression-free survival of three months and overall survival of only nine months.One of the alternatives considered is the standard combination of cisplatin with a vinca alkaloid, the vinorelbine. We consider the selection of patients candidates for this treatment critical for therapeutic success, and thus, to improve response rates (identify more responsive tumors) and reduce the toxicity of treatment (sparing the patients from ineffective, unresponsive and toxic tratment), it is necessary to evaluate predictors of treatment response, which may even have some prognostic use.The expression of ERCC1 (Excision Repair Cross-Complementing Group 1) is associated with a greater capacity for DNA repair in human cancers, and this marker could be used as a predictor of resistance to cisplatin. However, the expression of ERCC1 could reduce the accumulation of mutations in DNA and favorably affect the progression of certain tumors, thus being a factor related to better prognosis. ’III tubulin (TUBB3), a tubulin isoform, appears to be related at least in part to resistance to antimicrotubule agents, but also to other drugs.In order to contribute to a better selection of patients are candidates for systemic chemotherapy consisting of vinorelbine with an agent derived from platinum in the palliative setting (incurable disease, relapse), this study will evaluate the prognostic and predictive value of response to clinical and histopathological features in patients with advanced NSCLC treated with cisplatin and vinorelbine, as well as explore the role of the expression of biological markers related to resistance to antimicrotubule agents (²III tubulin) and mechanisms of DNA repair (ERCC1).