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Oncol Rep ; 32(3): 887-92, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24994673

RESUMO

Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin (LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum χ2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Orotato Fosforribosiltransferase/metabolismo , Administração Oral , Adulto , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/farmacologia , Humanos , Leucovorina/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida
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