Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression:: A phase III trial in non-small-cell lung cancer
Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression:: A phase III trial in non-small-cell lung cancer
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DOI：
10.1200/jco.2006.09.7915
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发表时间：
2007-07-01
影响因子：
45.3
通讯作者：
Rosell, Rafael
中科院分区：
文献类型：
--
作者：
Cobo, Manuel;Isla, Dolores;Rosell, Rafael
虽然目前转移性非小细胞肺癌（NSCLC）的治疗方案依赖于以顺铂为基础的化疗，但个体化的治疗方法可能会提高疗效或减少不必要的毒性。切除修复交叉互补1（ERCC1）与顺铂耐药相关。我们假设，分配顺铂治疗前ERCC1 mRNA水平的基础上，将提高respons.Patients和MethodsFrom 2001年8月至2005年10月，444 IV期NSCLC患者参加。从预处理活检组织中分离RNA，并进行定量实时逆转录酶PCR测定以确定ERCC1 mRNA表达。在ERCC1评估之前，患者以1：2的比例随机分配到对照组或基因型组。对照组患者接受多西他赛加顺铂治疗。在基因型组中，ERCC1水平低的患者接受多西他赛加顺铂治疗，ERCC1水平高的患者接受多西他赛加吉西他滨治疗。主要终点是总体客观responseres.ResultsOf 444例患者入组，78（17.6%）去了研究前接受一个周期的化疗，主要是由于肿瘤组织ERCC1 mRNA评估不足。其余346例可评估的反应，客观反应是由53例（39.3%）在对照组和107例（50.7%）在基因型手臂（P = 0.02）。结论ERCC1 mRNA表达的患者肿瘤组织中的评估是可行的，在临床环境中，并预测多西他赛和顺铂的反应。有必要进行更多的研究来优化小肿瘤样本中ERCC1分析的方法，并完善预测患者结局的多生物标志物谱。
PurposeAlthough current treatment options for metastatic non-small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response.Patients and MethodsFrom August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate.ResultsOf 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02).ConclusionAssessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.