乳腺癌易感基因1和受体相关蛋白80 mRNA表达水平指导肺癌患者个体化治疗的多中心随机对照临床研究

摘要

[Abstrca t] Objective BRCA 1 ( breast cancer susceptibility gene 1) and RAP80 ( receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes .A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression.Methods Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm.Patients in the control arm received docetaxel/cisplatin; in the experimental arm , patients with low RAP 80 expression received gemcitabine/cisplatin ( Arm 1 ) , those with intermediate/high RAP 80 expression and low/intermediate BRCA 1expression received docetaxel/cisplatin ( Arm 2 ) , and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3).The primary end point was progression-free survival (PFS).Results 226 patients were screened and 124 were randomized in this trial.ORR in the four subgroups was 22.6%, 48.4%, 30.3%and 19.2%, respectively (P=0.08);PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84).The common adverse effects included neutropenia , nausea, anemia and fatigue.Conclusions No statistically significant difference of ORR , PFS or OS is observed in the experimental arms compared with the control arm .Patients with low RAP 80 mRNA levels have a trend of better survival and higher response rate to gemcitabine /cisplatin chemotherapy .%目的：探讨乳腺癌易感基因1（ BRCA1）和受体相关蛋白80（ RAP80）mRNA 表达水平在肺癌患者个体化治疗中的指导作用。方法采用1∶3随机表法，将符合入组标准的进展期非小细胞肺癌（NSCLC）患者分为对照组和试验组，其中试验组根据BRCA1和RAP80 mRNA表达水平分为试验1组（RAP80 mRNA低表达， BRCA1 mRNA水平无要求）、试验2组（RAP80 mRNA中、高表达且BRCA1 mRNA中、低表达）和试验3组（RAP80 mRNA中、高表达且BRCA1 mRNA高表达）。对照组采用多西他赛＋顺铂方案化疗，试验1组采用吉西他滨＋顺铂方案化疗，试验2组采用多西他赛＋顺铂方案化疗，试验3组采用多西他赛单药化疗，比较各组患者的客观缓解率（ ORR）、疾病控制率（ DCR）、无进展生存时间（ PFS）、总生存时间（ OS）和不良反应。结果有226例患者进行筛选，最终入组患者124例。其中对照组31例，试验1组32例，试验2组33例，试验3组28例。对照组、试验1组、试验2组和试验3组患者的ORR分别为22．6％、48．4％、30．3％和19．2％，差异无统计学意义（ P＝0．08）。对照组、试验1组、试验2组和试验3组患者的DCR分别为64．5％、83．9％、63．6％和69．2％，差异无统计学意义（ P＝0．25）。对照组、试验1组、试验2组和试验3组患者的中位PFS分别为4．74、5．59、3．78和2．73个月，差异无统计学意义（ P＝0．55）。对照组、试验1组、试验2组和试验3组患者的中位OS 分别为10．82、14．44、10．86和108．6个月，差异无统计学意义（ P＝0．84）。常见的不良反应有粒细胞减少、消化道反应、贫血和乏力。结论试验组患者在PFS、RR及OS上较对照组无优势，但RAP80 mRNA低表达且接受吉西他滨＋顺铂化疗的患者较其他患者有预后较好的趋势。