Preliminary indication of survival benefit from ERCC1 and RRM1-tailored chemotherapy in patients with advanced nonsmall cell lung cancer: evidence from an individual patient analysis.
Preliminary indication of survival benefit from ERCC1 and RRM1-tailored chemotherapy in patients with advanced nonsmall cell lung cancer: evidence from an individual patient analysis.
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DOI：
10.1002/cncr.26522
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发表时间：
2012-05-01
期刊：
影响因子：
6.2
通讯作者：
Bepler G
中科院分区：
文献类型：
--
作者：
Simon GR;Schell MJ;Begum M;Kim J;Chiappori A;Haura E;Antonia S;Bepler G
ERCC 1和RRM 1分别是预测铂类药物和吉西他滨敏感性或耐药性的分子决定因素。使用这些分子决定因素的定制治疗在先前报道的II期试验中表明患者受益。在这里，我们报告了一个个体患者分析的前瞻性累积的患者治疗与“个性化治疗”的方法与其他“标准”非定制的方法。在H Lee Moffitt癌症中心（HLMCC）进行的4项II期临床试验中，招募了具有结节转移性疾病且ECOG PS为0/1的NSCLC患者：试验A）卡铂/吉西他滨一线治疗，随后为多西他赛;试验B）多西他赛和吉非替尼治疗70岁或以上患者;试验C）卡铂/紫杉醇/阿曲生坦联合治疗;试验D）基于ERCC 1和RRM 1的个性化治疗（PT）。低RRM 1/低ERCC 1患者接受吉西他滨/卡铂;低RRM 1/高ERCC 1，吉西他滨/多西他赛;高RRM 1/低ERCC 1，多西他赛/卡铂;高RRM 1/高ERCC 1，长春瑞滨/多西他赛。将试验A、B和C中接受治疗的患者合并在一起，并作为“标准治疗”组进行分析。参加试验D的患者被称为“个性化治疗”组。个体患者数据更新至2011年2月8日。使用Kaplan-Meier方法估计总生存期（OS）和无进展生存期（PFS）。缓解（44% vs. 22%; p=0.002）、OS（中位OS; 13.3个月vs. 8.9; p= 0.016）和PFS（中位PFS 7.0 vs. 4.3; p= 0.03）均出现统计学显著性改善。该个体患者分析表明，ERCC 1和RRM 1定制选择的一线治疗比标准治疗选择方法提高了生存率。
ERCC1 and RRM1 are molecular determinants that predict sensitivity or resistance to platinum agents and gemcitabine, respectively. Tailored therapy using these molecular determinants suggests patient benefit in a previously reported phase II trial. Here we report an individual patient analysis of prospectively accrued patients treated with the ‘personalized therapy’ approach versus other ‘standard’ non-customized approaches. NSCLC patients with extranodal metastatic disease and an ECOG PS of 0/1 were accrued to four phase II clinical trials conducted at the H Lee Moffitt Cancer Center (HLMCC): Trial A) carboplatin/gemcitabine first-line followed by docetaxel; Trial B) docetaxel and gefitinib therapy in patients aged 70 years or older; Trial C) combination therapy with carboplatin/paclitaxel/atrasentan; Trial D) personalized therapy (PT) based on ERCC1 and RRM1. Patients with low RRM1/low ERCC1 received gemcitabine/carboplatin; low RRM1/high ERCC1, gemcitabine/docetaxel; high RRM1/low ERCC1, docetaxel/carboplatin; high RRM1/high ERCC1, vinorelbine/docetaxel. Patients treated on trials A, B and C were pooled together and analyzed as the ‘standard therapy’ group. Patients accrued to trial D were called the ‘personalized therapy’ group. Individual patient data were updated as of 02/08/11. Overall Survival (OS) and progression free Survival (PFS) were estimated using the Kaplan-Meier method. There was a statistically significant improvement in responses (44% versus 22%; p=0.002), OS (median OS; 13.3 months vs. 8.9; p= 0.016) and PFS (median PFS 7.0 vs. 4.3; p= 0.03). This individual patient analyses suggests that ERCC1 and RRM1 tailored selection of first-line therapy improves survival over standard treatment selection approaches.
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影响因子：
45.3
作者：
Scagliotti, Giorgio Vittorio;Parikh, Purvish;Gandara, David
通讯作者：
Gandara, David
影响因子：
45.3
作者：
Bepler, Gerold;Kusmartseva, Irina;Simon, George
通讯作者：
Simon, George
影响因子：
158.5
作者：
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通讯作者：
Johnson, David H.
DOI：
10.1016/j.biocel.2007.05.006
发表时间：
2007-01-01
影响因子：
4
作者：
Simon, George R.;Ismail-Khan, Roohi;Bepler, Gerold
通讯作者：
Bepler, Gerold
影响因子：
11.5
作者：
Chiappori, Alberto A.;Haura, Eric;Bepler, Gerold
通讯作者：
Bepler, Gerold