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还原型叶酸载体(RFC)作为晚期非小细胞肺癌(NSCLC)中培美曲塞治疗反应的预测标志物。

Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC).

作者信息

Alvarez-Fernandez Carlos, Perez-Arnillas Quionia, Ruiz-Echeverria Lucrecia, Rodriguez-Rubi David, Sanchez-Lorenzo Luisa, Li-Torres Walter, Izquierdo-Manuel Marta, Berros Jose P, Luque-Cabal Maria, Jimenez-Fonseca Paula, Villanueva-Palicio Noemi, Esteban-Gonzalez Emilio

机构信息

Department of Medical Oncology, Hospital Universitario Central de Asturias, Celestino Villamil s/n. 33006, Oviedo, Asturias, Spain,

出版信息

Invest New Drugs. 2014 Apr;32(2):377-81. doi: 10.1007/s10637-013-9992-1. Epub 2013 Aug 4.

Abstract

INTRODUCTION

RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC.

METHODS

The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples.

RESULTS

RFC expression was detected in 16 (33 %) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p = 0.926) and median OS (11.7 vs 4.8; p = 0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p = 0.039).

CONCLUSIONS

These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.

摘要

引言

还原叶酸载体(RFC)是哺乳动物细胞中叶酸辅因子和抗叶酸治疗药物的主要转运系统。本研究的目的是评估接受培美曲塞治疗的晚期非小细胞肺癌(NSCLC)患者中RFC表达的预测价值。

方法

本研究在48例接受过二线和三线培美曲塞单药治疗的晚期NSCLC患者中进行。使用两步免疫组织化学染色模型在石蜡包埋组织样本中评估RFC表达。

结果

在16例(33%)患者中检测到RFC表达。在总体人群中,无进展生存期(PFS)中位数和总生存期(OS)中位数分别为3.3个月和6.5个月。RFC表达阳性的患者亚组的PFS中位数(4.5个月对2.8个月;p = 0.926)和OS中位数(11.7个月对4.8个月;p = 0.150)有更好的趋势。在腺癌组织学且有RFC表达的患者中,培美曲塞治疗后的OS中位数为14.4个月,而腺癌但无RFC表达的患者为5.0个月(p = 0.039)。

结论

这些结果提示RFC表达与抗叶酸药物(培美曲塞)治疗反应之间可能存在关联,且与肿瘤组织学无关。需要进一步研究来证实这些结果。

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