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Am J Clin Oncol ; 37(2): 117-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23211222

RESUMO

PURPOSE: To investigate the feasibility of personalizing chemotherapy in patients with rectal cancer. METHODS: Patients with cT3 or cN1 and cM0 rectal cancer were eligible. A set of 6 molecular markers including KRAS, BRAF, and PI3K mutations and expression of topoisomerase-1 (Topo-1), ERCC-1, and thymidylate synthase (TS) using immunohistochemistry were performed in a tumor biopsy. All patients were treated with capecitabine 625 to 825 mg/m/12 h M-F in combination with either irinotecan or oxaliplatin based on Topo-1 and ERCC-1 expression plus either bevacizumab or cetuximab based on the mutation status. All patients received intensity-modulated radiation therapy. A surgery was performed 6 to 8 weeks after the treatment. RESULTS: Fifteen patients (94%) had T3 tumor and 10 (62%) N+ disease of 16 patients enrolled. In all patients, the full set of markers was analyzed within 10 days. Seven patients had K-ras mutation, and 4, 5, and 10 expressed Topo-1, ERRC-1 and TS, respectively. All patients had wild-type BRAF and PI3K tumors. The median time from obtaining informed consent to the treatment period was 18 days and all patients completed the chemoradiation treatment. Fifty percent achieved a complete pathologic response to treatment. Four patients (25%) developed grade 3 proctitis or diarrhea. There were no relevant surgical complications. Sixty-nine percent of the patients received adjuvant XELOX. CONCLUSIONS: The individualization of neoadjuvant chemotherapy in patients with rectal cancer is feasible and leads to a high rate of pathologic response.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia de Alvo Molecular/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina , Cetuximab , Quimiorradioterapia , DNA Topoisomerases Tipo I/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Oxaloacetatos , Fosfatidilinositol 3-Quinases , Projetos Piloto , Medicina de Precisão/métodos , Estudos Prospectivos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Retais/genética , Neoplasias Retais/cirurgia , Resultado do Tratamento , Proteínas ras/genética
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