[Lancet]化疗和厄洛替尼交叉治疗肺癌可行

    6月17日FASTACT-2研究内容在线发表于《The Lancet Oncology》。此前，FASTACT这项随机，安慰剂对照的2期临床研究结果已经表明：化疗和厄洛替尼联合交叉能够显着延长晚期非小细胞肺癌患者的无进展生存期（PFS）。因此研究者们开展FASTACT-2研究，在相似的患者人群中开展3期研究。（The Lancet Oncology, Early Online Publication, 17 June 2013）


研究内容：

       在这项3期临床试验中，纳入未经处理的IIIB/IV期非小细胞肺癌患者，通过一个交互式网络应答系统以1:1的比例随机分配，按照疾病分期，肿瘤组织学，吸烟状况以及化疗方案进行分层。化疗联合厄洛替尼组患者接受：6个疗程吉西他滨（1250 mg/m2，d1、d8，静脉注射）联合铂类（卡铂 5×曲线下面积或顺铂75mg/m2，静脉注射，d1）联合穿插的厄洛替尼（150mg/d,d15-28），化疗联合安慰剂组则接受化疗及安慰剂口服，每4周为1周期。

       一个独立的小组负责监测数据和安全，交互式网络应答系统公司外的任何人都按盲法接受治疗的分配。患者继续接受厄洛替尼或安慰剂直到疾病进展或不可接受的毒性或死亡，所有安慰剂组的患者在疾病进展的时候将提供二线厄洛替尼的治疗。主要终点是意向性治疗人群的PFS。


具体结果：

       从2009年4月29日至2010年9月9日，共451例患者被随机分配到化疗联合厄洛替尼组（n=226）或化疗加安慰剂组（n=225）。化疗联合厄洛替尼组与化疗加安慰剂组相比，PFS得到显着延长（中位PFS 7.6个月[95％CI 7.2 -8.3]，VS 6.0个月[5.6 -7.1]，风险比HR为0.57 [0.47-0.69]，P<0.0001）。化疗联合厄洛替尼与化疗加安慰剂组患者的中位总生存期分别为18.3个月（16.3-20.8）个月和15.2个月（12.7-17.5），HR 0.79[0.64 -0.99]，P=0.0420。

       只有EGFR基因突变的患者在治疗中获益（中位PFS16.8个月[12.9-20.4] vs 6.9个月[5.3-7.6，HR 0.25 [0.16-0.39]，P <0.0001；中位总生存期31.4个月[22.2-未达到，vs 20.6个月[14.2 -26.9]，HR0.48[0.27-0.84，P=0.0092）。

       222例化疗加安慰剂组患者中，76例（34%）出现严重不良事件报告，化疗联合厄洛替尼组的226例中出现69例（31%）。最常见的3级或以上的不良反应为中性粒细胞减少（65例[29％]和55例[25％]），血小板减少症（32％[14％]和31 [14％]）和贫血（26 [12％]和21 [10％]）。

       综上，我们可以看出，对于EGFR突变阳性或EGFR突变状态未知的非小细胞肺癌患者来讲，一线选择化疗和厄洛替尼穿插使用是可行的。

source: http://news.medlive.cn/cancer/info-progress/show-49828_53.html

Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial

Summary

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Background
The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population.


Methods
In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m2 on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m2 on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15—28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779.


Findings
From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2—8·3], vs 6·0 months [5·6—7·1], hazard ratio [HR] 0·57 [0·47—0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3—20·8) and 15·2 months (12·7—17·5), respectively (HR 0·79 [0·64—0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9—20·4] vs 6·9 months [5·3—7·6], HR 0·25 [0·16—0·39]; p<0·0001; median overall survival 31·4 months [22·2—undefined], vs 20·6 months [14·2—26·9], HR 0·48 [0·27—0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively).


Interpretation
Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status.


Funding
F Hoffmann-La Roche.

顶上去

广东的吴一龙好像在2008年的时候就开始相关的临床试验，不知道结果如何

这一年半内到底做了几次化疗啊?一共6次?

知难而进 发表于 2013-7-3 07:39

                               
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这一年半内到底做了几次化疗啊?一共6次?

一年半是整个研究的时间周期嘛 期间不断有患者入组
每个病人只接受了连续6个疗程的化疗：
Drug: erlotinib [Tarceva]
150mg po on days 15-28 of each 4 week cycle until disease progression
Drug: gemcitabine
1250mg/m2 iv on days 1 and 8 of each 4 week cycle for 6 cycles
Drug: Platinum chemotherapy (cisplatin or carboplatin)
cisplatin --75mg/m2 oon day 1 of each 4 week cycle for 6 cycles or carboplatin--5xAUC on day 1 of each 4 week cycle for 6 cycles

4周一个cycle
一共6个cycle