Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site
Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site
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DOI：
10.1200/jco.18.00771
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发表时间：
2019-03-01
影响因子：
45.3
通讯作者：
Nakagawa, Kazuhiko
中科院分区：
文献类型：
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作者：
Hayashi, Hidetoshi;Kurata, Takayasu;Nakagawa, Kazuhiko
目的：虽然基因表达谱是一种很有前途的诊断技术，可以确定未知原发部位癌症（CUP）患者的起源组织，但目前还没有临床试验将这种方法指导的部位特异性治疗与经验化疗进行比较。因此，我们进行了一项随机研究，以评估与经验化疗相比，这种部位特异性治疗是否能改善先前未经治疗的CUP患者的预后。患者与方法通过微阵列分析进行全面的基因表达谱分析，并应用已建立的算法预测肿瘤起源。CUP患者随机分配（1:1）接受标准部位特异性治疗或经验性紫杉醇加卡铂（PC）治疗。主要终点为1年生存率。结果随机分配130例患者，有足够的活检组织进行分子分析。分别对部位特异性治疗组和经验性PC组的50例和51例患者进行疗效分析。最常见的预测癌症类型是胰腺癌（21%）、胃癌（21%）和淋巴瘤（20%）。部位特异性治疗和经验PC的1年生存率分别为44.0%和54.9% （P = .264）。部位特异性治疗的中位总生存期和无进展生存期分别为9.8个月和5.1个月，而经验性PC的中位总生存期和无进展生存期分别为12.5个月和4.8个月(P = .896和。550年,分别)。中位总生存期（16.7 v 10.6个月，P = 0.116）和无进展生存期（5.5 v 3.9个月，P = 0.018）在预测高反应性肿瘤类型中优于低反应性肿瘤类型。结论：与经验PC相比，基于微阵列分析的部位特异性治疗并未导致1年生存率的显着改善，尽管对原始部位的预测似乎具有预后价值。
PURPOSEAlthough gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP.PATIENTS AND METHODSComprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate.RESULTSOne hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC (P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC (P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types.CONCLUSIONSite-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.