中山大学连发两篇高影响因子论文 解析癌症作用机制

　　生物通报道：来自中山大学附属肿瘤医院的研究人员近期接连发表文章，分别公布了埃克替尼Ⅲ期ICOGEN研究结果，以及PET/CT在鼻咽癌的临床运用新发现。相关成果公布在The Lancet Oncology（影响因子为 25.117）和Journal of Clinical Oncology （影响因子为 18.038）。

在第一篇文章中，中山大学附属肿瘤医院，中国医科院肿瘤医院等处的研究人员采用随机、双盲双模拟、平行对照、多中心评价埃克替尼和吉非替尼治疗既往接受过一个或两个化疗的局部晚期或转移的非小细胞肺癌患者的疗效和安全性Ⅱ/Ⅲ期临床试验。

文章第一作者为中国医科院肿瘤医院石远凯教授和中山大学附属肿瘤医院张力教授，通讯作者为孙燕院士。

盐酸埃克替尼是一种口服的EGFR酪氨酸激酶抑制剂，早期临床研究显示其具有抗肿瘤活性，且毒性反应可以接受。研究人员收集了来自中国的27个中心，年龄介于18至75岁之间，既往对一种或多种基于铂类的化疗方案无反应的晚期非小细胞肺癌患者。

受试者随机分为两组，一组接受盐酸埃克替尼治疗（125mg每日三次），另一组接受吉非替尼治疗（250mg每日一次），直至疾病出现进展或出现不可耐受的毒性反应。

研究者发现，与吉非替尼组的受试者相比，盐酸埃克替尼组的受试者的药物相关不良反应事件更少，两者差异具有显著统计学意义，在药物相关性腹泻方面尤为明显。研究结果指出，对于既往接受过治疗的晚期非小细胞肺癌患者而言，盐酸埃克替尼是一种可供选择的新治疗方法。

这些研究结果曾以摘要形式发表于2011年和2012年的美国肿瘤学年会（ASCO）、世界肺癌大会（WCLC）和欧洲肿瘤年会（ESMO）等学术会议上交流。

另外一篇文章中，肿瘤防治中心鼻咽科麦海强教授研究团队发现PET/CT运用于N2-3分期并且血浆EBV DNA ≥4000copies/ml的鼻咽癌人群，从治疗方法的改善和经济成本方面考虑，该人群获益最大，此项研究成果对于指导PET/CT在鼻咽癌的临床运用具有重要意义。

鼻咽癌(NPC) 在中国华南地区及东南亚较为流行。放疗为该病的主要治疗手段。尽早发现远端转移对于精准分期并获得最佳控制不可或缺。尽管2011年版美国国家综合癌症网络指南认为，对于WHO 2至3型/N2-3 期病情的NPC患者，推荐考虑[18F]氟脱氧葡萄糖正电子发射计算机断层扫描及计算机断层扫描(PET/CT)进行远端转移检测，但该观点鲜有研究支持。

研究人员收集了583例患者，共发现86例(14.8%)患者存在远端转移；其中由PET/CT手段检测出71例(82.6%)，CWU手段检测出31例(36.0%)。多变量分析表明，N晚期及治疗前EBV DNA水平(为远端转移的显著风险因素。对于极低风险患者的远端转移检测，PET/CT并不优于CWU (N0-1 且 EBV DNA ，但对于低风险患者(N0-1 且EBV DNA ≥ 4,000拷贝数/mL及N2-3且EBV DNA <4,000拷贝数/mL; P =.039)及中等风险患者(N2-3 期且EBV DNA ≥ 4,000拷贝数/mL; P< .001)，PET/CT优于CWU。

与传统的分期方法相比，PET/CT更可能检测出NPC患者出现的远端转移情况。这一研究结果表明，N2-3期且EBV DNA ≥ 4,000 拷贝数/mL的患者可在费用及控制方面取得最大获益。

（生物通：万纹）

原文摘要：

Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial

Background
Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer.
Methods
In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18—75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506.
Findings
400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67—1·05; median progression-free survival 4·6 months [95% CI 3·5—6·3] vs 3·4 months [2·3—3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033).

Prospective Study of Tailoring Whole-Body Dual-Modality [18F]FluorodeoxyglucosePositron Emission Tomography/Computed Tomography With Plasma Epstein-Barr VirusDNA for Detecting Distant Metastasis in Endemic Nasopharyngeal Carcinoma atInitial Staging