易瑞沙耐药后的解决方案，请大家都来找出路

jimmy112199 · 发表于 2007-7-20 08:20:24

这是韩国的IRESSA后用TARCEVA的结果，有几点值得注意：1) IRESSA 和 TARCEVA 同时用药没有特别效果。There appears to be no benefit from combining Tarceva with Iressa for the
treatement of NSCLC2) 停药4个月没有提用化疗。 3) 给出的再次耐药的中位时间(125天)和中位生存期(158天)。 Tarceva® May Be
Effective in Patients with NSCLC Progressing after Responding to Iressa®

Researchers from <st1country-region><st1place>South Korea</st1place></st1country-region>
have reported that Tarceva®
(erlotinib) may be effective in patients with stable non–small cell lung cancer
(NSCLC) after
treatment Iressa® (gefitinib). The details of this study were reported in the <st1date month="6" day="20" year="2007">June 20, 2007</st1date> issue of the Journal
of Clinical Oncology.

Tarceva and
Iressa are tyrosine kinase inhibitors that are active in a subset of patients
with NSCLC. Responsive tumors were likely to be adenocarcinomas or
bronchio-alveorlar carcinomas and occurred more frequently in non-smokers and
women. Responses also occur more frequent in patients with specific mutations
of EGFR. There appears to be no benefit from combining Tarceva with Iressa for the
treatement of NSCLC but sequential use has not been reported before.

This trial included 21 patients who had received two or three prior
chemotherapy regimens and prior treatment with Iressa. Patients who experienced
cancer progression within four months of discontinued treatment with Iressa
were then treated with Tarceva.
Eleven patients were female, 16 had adenocarcinoma and 11 were never smokers.
Five of 17 evaluable patients had EGFR mutations.

The overall response rate was 10% with disease control in 29%. The median
disease control was 125 days. Median overall survival was 158 days.

<ul type="disc"><li class="MsoNormal">&#160

atients who
experienced disease stabilization while being treated with Iressa had a
75% rate of cancer control when treated with Tarceva.</li><li class="MsoNormal">&#160

atients who had not
experienced disease stabilization while being treated with Iressa had only
a 17.6% rate of cancer control when treated with Tarceva.</li><li class="MsoNormal">&#160

atients lacking EGFR
 mutations who experienced disease stabilization while being treated with
 Iressa had significantly higher rates of cancer control and cancer
 regression than the same group of patients with EGFR mutations.</li></ul>

The researchers concluded that patients with NSCLC who had prior disease
control with Iressa and do not have EGFR mutations appear to have benefit from
treatment with Tarceva
once their cancer progresses. Patient with recurrent NSCLC may wish to speak
with their physician regarding their individual risks and benefits of treatment
with Tarceva.

Comments: These data suggest that
sequential treatment of NSCLC with Iressa and Tarceva can be effective if patients had an
initial response.

Reference: Chul Cho B, Im C-K, Park M-S,
et al. Phase II study of erlotinib in advanced non–small cell lung cancer after failure of gefitinib. Journal
of Clinical Oncology. 2007;25:2528-2533. 

<op> </op>

<op> </op>

非小细胞肺癌患者伊丽沙®有效后又进展，它赛瓦®仍可有效<op></op>

<op> </op>

研究者来自南韩的报道，
它赛瓦®,可有效地治疗伊丽沙®治疗耐药后稳定期非小细胞肺癌( NSCLC ) . 

<op> </op>

详情本研究报告于2007年6月20日发行的临床肿瘤学杂志. 

它赛瓦和伊丽沙是酪氨酸激酶抑制剂, ，对肺腺癌，或支气管癌alveorlar ,

非吸烟者，，女性，患者有特定的突变受体.

,它赛瓦和伊丽沙联合治疗肺癌显然并没有特别效果，但使用时序还没有被报导过. 

<op> </op>

这项试验包括21个病人，病人事先已受到两个或三个前化疗，再接受伊丽沙治疗. 病人出现癌症的进展，中止伊丽沙治疗达四个月，再用它赛瓦.


<op> </op>

11例患者均为女性, 16例腺癌，和11名从未吸烟者. 17人中5人有EGFR突变. 整体有效率为10% ,疾病控制率在29% . 中期疾病控制是125天. 平均存活期为158天. 

<op> </op>

*病人经历IRRESA疾病稳定的, 用它赛瓦治疗75%治疗有效.

 *病人用IRESSA后，从未经历过疾病稳定, 的，, 用它赛瓦治疗，仅有17.6%
, 有效.

 *患者缺乏EGFR突变的人，经历了疾病稳定后,
比EGFR突变的人，<op></op>

有明显较高比率癌症控制。<op></op>

研究者的结论是：非小细胞肺癌患者用伊丽沙有效，并没有EGFR突变的，癌症进展后.似乎会得益于它赛瓦，
患者肺癌复发不妨跟自己的医生讨论，它赛瓦治疗对他们的风险和益处.

 评论: 这些数据表明,序贯使用治疗肺癌药物Iressa,它赛瓦是可以有效的,如果患者IRESSA治疗有效。.

 参考:吉町二,肌肉注射三钾,公园米S等. 

在晚期非小细胞肺癌IRESSA治疗失败后，用TARCEVA的第二阶段研究. 临床肿瘤学杂志. 2007年; 25:2528-2533 .

jli999 · 发表于 2007-7-20 12:51:16

非常感谢jimmy112199提供的译文。这个信息对于易瑞沙耐药后的患者太重要了，在此之前大家知道的都是IRESSA及它赛瓦因为针对的是同一靶点，所以易瑞沙耐药后通常不再建议用它赛瓦。另外，关于EGFR突变,研究者的结论是“非小细胞肺癌患者用IRESSA有效，并没有EGFR突变的，癌症进展后.似乎会得益于它赛瓦”，说明没有EGFR突变的，易瑞沙仍可能有效；而没有EGFR突变的，IRESSA耐药后它塞瓦的有效率可能更高。       加油啊!尽管目前的这些研究和数据只能作为一种参考，但对我们仍是不小的鼓舞。再次表示感谢！

我爱妈妈 · 发表于 2007-7-20 14:30:12

TO：东方谢谢你的关心。昨天妈妈来北京看了中医专家，我也看到了CT片子。上面写道（大概内容）：1、左肺上叶下舌段仍见不规则肿物影，边界不清，肿瘤较前略有缩小；2、左肺仍见多发结节状，高密度影；考虑转移瘤，大小、数目大部病变同前相仿，左肺上叶结节较前略有增多，右肺上叶前段见一结节，考虑转移。3、右肺下叶后基底段见斑片状高密度影，考虑炎性病变。4、纵隔4R、<chmetcnv wst="on" tcsc="0" numbertype="1" negative="False" hasspace="False" sourcevalue="4" unitname="l">4L</chmetcnv>、5区、7区见多发性小结节，大者径小于<chmetcnv wst="on" tcsc="0" numbertype="1" negative="False" hasspace="False" sourcevalue="1" unitname="cm">1.0cm</chmetcnv>，同前大致相仿。5、胸椎、肋骨破坏大致同前。6、左胸腔积液较前减少，左侧胸膜增厚；右侧胸腔积心包未见积液中医的意见与西医大夫一致：暂时不用做任何其它治疗，继续观察并服用易瑞莎，辅助以草药以及益肺清化膏但妈妈的感觉没有以前好，痛感以及频度都比过去强，而且现在气短、无力、咳嗽加重、小便有些费劲谢谢东方的建议，重新考虑吃英国版易瑞莎。请教各位：对于以上报告，大家有什么建议吗？我自己认为必须采取一定措施，不能坐等；但医生却说，问题不大，观察观察。弄不明白，好郁闷啊

小路 · 发表于 2007-7-21 07:27:36

谢谢jimmy,你的译文太重要了, 我想问jimmy: 易瑞沙耐药后直接上它沙瓦会有效吗？“易瑞沙稳定期用它沙瓦会有效……”什么叫稳定期？是指“易”耐药后重上化疗后的稳定期吗？具体多长时间？这句话含义是什么？

[此贴子已经被作者于2007-7-23 16:55:18编辑过]

东方 · 发表于 2007-7-23 23:34:34

感谢jimmy,对于上述报告我有同感，我妈妈就是在易瑞沙耐药后，用了两期力比泰单疗无效后立即转用特罗凯，争取了3个月有效期，虽然现在再度出现耐药，但我上周开始进行DCA的服用后目前感到有效。也就是说，在易瑞沙耐药后，再次化疗争后转用特罗凯仍有效。

小路 · 发表于 2007-7-24 06:23:32

东方，目前服用DCA成功的案例有吗？有机会给大家讲讲。谢了！

jimmy112199 · 发表于 2007-7-24 07:49:25

<div class="msgheader">QUOTE:</div><div class="msgborder">以下是引用小路在2007-7-21 7:27:36的发言： 谢谢jimmy,你的译文太重要了, 我想问jimmy: 易瑞沙耐药后直接上它沙瓦会有效吗？“易瑞沙稳定期用它沙瓦会有效……”什么叫稳定期？是指“易”耐药后重上化疗后的稳定期吗？具体多长时间？这句话含义是什么？ 
</div>我也不太清楚，原文是 within four months of discontinued treatment with Iressa, 四个月不连续的IRESSA治疗。 但查看了他们的另一论文，好像是直接上 TARVECA。因为文中报道的中位癌症无进展只有60天。 <h1>A
phase II study of erlotinib treatment in advanced non-small cell lung
cancer after failure of gefitinib: Is a clinical benefit still
achievable?</h1>


<table width="98%" cellspacing="0" cellpadding="0" border="0">
<tbody><tr>
 <td width="99%" valign="top">
 <table width="100%" cellspacing="3" cellpadding="0" border="0">

 <tbody><tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>
 Sub-category:
 </h3></td>
 <td width="99%" valign="top"><h4>
 <a href="http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_category_abstracts_view&confID=47&subCatID=47">
 Non-Small Cell Lung Cancer
 </a>
 </h4></td>
 </tr>


 <tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>
 Category:
 </h3></td>
 <td width="99%" valign="top"><h4>
 Lung Cancer
 </h4></td>
 </tr>

 <tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>
 Meeting:
 </h3></td>
 <td width="99%" valign="top"><h4>
 <a href="http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_meeting_categories_view&confID=47">
 2007 ASCO Annual Meeting
 </a>
 </h4></td>
 </tr>
 </tbody></table>
 </td>
 <td width="1%" valign="top" nowrap="nowrap">

 <h4>
 <a target="_new" href="http://www.asco.org/portal/site/ASCO/template.RAW/menuitem.34d60f5624ba07fd506fe310ee37a01d/?javax.portlet.tpst=0e116779df458209ada2be0aee37a01d_ws_RW&javax.portlet.prp_0e116779df458209ada2be0aee37a01d_viewID=abst_detail_rawview&javax.portlet.begCacheTok=com.vignette.cachetoken&javax.portlet.endCacheTok=com.vignette.cachetoken&index=n&confID=47&abstractID=30381">
 <img border="0" alt="" src="http://www.asco.org/portal/beans/virtualmeeting/images/print.gif"/>
 Printer Friendly
 </a>
 </h4>
 <h4>
 <a href="http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&index=y&abstractID=30381#">
 <img border="0" alt="" src="http://www.asco.org/portal/beans/reutersnews/images/email.gif"/>
 E-Mail Article
 </a>
 </h4>

 </td>
</tr>
</tbody></table>

<table width="98%" cellspacing="3" cellpadding="0" border="0"><tbody><tr><td colspan="2"><img width="1" height="10" border="0" alt="" src="http://www.asco.org/portal/beans/virtualmeeting/images/clear.gif"/></td></tr>
<tr><td id="vmtablerowdark" colspan="2"><img width="1" height="1" border="0" alt="" src="http://www.asco.org/portal/beans/virtualmeeting/images/clear.gif"/></td></tr>
<tr><td colspan="2"><img width="1" height="10" border="0" alt="" src="http://www.asco.org/portal/beans/virtualmeeting/images/clear.gif"/></td></tr>

<tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>Abstract No:</h3></td>
 <td width="99%" valign="top">
 <h4>7609</h4>
 </td>
</tr>

<tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>Citation:</h3></td>
 <td width="99%" valign="top">
 <h4>Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 7609</h4>
 </td>
</tr>

<tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>Author(s):</h3></td>
 <td width="99%" valign="top">
 <h4>B. Cho, C. Im, H. Choi, S. Shin, J. Sohn, J. Kim, S. Kim, J. Moon, Y. Kim, J. Kang</h4>
 </td>
</tr>
<tr>
 <td width="1%" valign="top" nowrap="nowrap"><h3>Abstract:</h3></td>
 <td width="99%" valign="top">
 <h4>Background:
To evaluate the efficacy and toxicity of erlotinib in patients (pts)
with advanced NSCLC who had progression after treatment with gefitinib.
Methods: The study included stage IIIB/IV recurrent or
metastatic NSCLC pts who have received 2 or 3 prior chemotherapy
regimens and showed documented disease progression during or within 4
months after treatment with gefitinib. Pts received erlotinib 150 mg
daily until disease progression or unacceptable toxicity. We analyzed
EGFR mutations and other genetic abnormality from available tumor
samples. Results: Pts and disease characteristics (n = 21)
included median age 56 years; number of prior chemotherapy regimens
(two, n=10; three, n=11); male (n=10); adenocarcinoma (n=15); and
smoking status (never, n=11; former, n=3; current, n=7). Among the 17
pts with tumor samples available, EGFR mutation were detected in 5
(29.4 %). The DCR and RR for all pts were 28.6% (95% CI, 16.7 to 59.6%)
and 9.5% (95% CI, 5.6 to 19.8%). All responders were EGFR nonmutants,
with long duration of disease control on prior gefitinib therapy
(>180 days). The median duration of disease control was 125 days
(95% CI, 73-261 days). The median progression-free survival and overall
survival were 60 days (95% CI, 43-77 days) and 158 days (95% CI,
141-175 days), respectively. Pts who had SD on gefitinib showed
significantly higher DCR (75% vs. 17.6% in non-SD pts,

= 0.050) and RR (50.0% vs. 0% in non-SD pts,

= 0.029). These pts also showed longer median PFS (140 vs. 37 days in non-SD pts,

= 0.005) and OS (not reached vs. 120 days in non-SD pts,

=
0.043). Among 17 pts with biomarker results available, EGFR nonmutants
who had SD on gefitinib showed significantly higher DCR (100% vs. 21.4%
in non-SD and/or EGFR mutants,

= 0.029) and RR (RR, 66.7 % vs. 0 % in non-SD and/or EGFR mutants,

= 0.022). Conclusions: Erlotinib seems to be a potential therapeutic option for the treatment of selected pts with gefitinib-nonresponsive,
EGFR nonmutant, advanced NSCLC. Response to erlotinib
<table cellpadding="1" border="1" id="&lcub;42C44746-BCFD-4697–8CC6-D678AF8CE792&rcub;" class="DisplayTable" col="3" tgroupstyle="zlj-abs"><tbody><tr><td colspan="1" rowspan="1">Response (RECIST criteria)</td>
<td align="center">No. of pts (n = 21)</td>
<td align="center">%</td></tr><tr><td colspan="1" rowspan="1">Complete response</td><td colspan="1" rowspan="1">0</td><td colspan="1" rowspan="1">0</td></tr><tr><td colspan="1" rowspan="1">

artial response</td><td colspan="1" rowspan="1">2</td><td colspan="1" rowspan="1">9.5</td></tr><tr><td colspan="1" rowspan="1">Stable disease</td><td colspan="1" rowspan="1">4</td><td colspan="1" rowspan="1">19</td></tr><tr><td colspan="1" rowspan="1">

rogressive disease</td><td colspan="1" rowspan="1">15</td><td colspan="1" rowspan="1">71.4</td></tr><tr><td colspan="1" rowspan="1">Disease control rate</td><td colspan="1" rowspan="1">6</td><td colspan="1" rowspan="1">28.6</td></tr><tr><td colspan="1" rowspan="1">95% CI,%</td><td colspan="1" rowspan="1"> </td><td colspan="1" rowspan="1">16.7-59.4</td></tr><tr><td colspan="1" rowspan="1">Overall response rate</td><td colspan="1" rowspan="1">2</td><td colspan="1" rowspan="1">9.5</td></tr><tr><td colspan="1" rowspan="1">95% CI,%</td><td colspan="1" rowspan="1"> </td><td colspan="1" rowspan="1">5.6-19.8</td></tr></tbody></table></h4></td></tr></tbody></table>

jimmy112199 · 发表于 2007-7-24 09:03:45

这里是意大利的一篇TARCEVA抗药后直接上IRESSA的文摘。 

Gefitinib (G) treatment outcome after progression on
erlotinib (E) in patients with advanced non-small cell lung cancer
(NSCLC).  Sub-category:     Non-Small Cell Lung Cancer  Category:    
Lung Cancer  Meeting:     2007 ASCO Annual Meeting

rinter Friendly  E-Mail Article  Abstract No:     18138 
Citation:     Journal of Clinical
Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20
Supplement), 2007: 18138  Author(s):     F. Grossi, A. Brianti, C. Defferrari, M.
Loprevite, G. Catania, P. Pronzato 
Abstract:     Background: Two case
reports describe a response to E after failure of G (Garfield DH, J Clin Oncol
2005) or to G after failure of E (Choong NW et al, Nat Clin Pract Oncol 2006)
in patients (pts) with advanced NSCLC. Otherwise, a limited experience in 5 pts
suggests that E is not effective in pts progressing on G (Viswanathan A et al,
Lung Cancer 2005). Aim of this study was the evaluation of response and time to
progression (TTP) in advanced NSCLC pts treated with G after failure of E.
Methods: Pts received G 250 mg/day after disease progression (PD) with E 150
mg/day. Pts accrual was stopped on August 2006 after the approval of E for use
in <st1country-region><st1place>Italy</st1place></st1country-region> and
the consequent closure of the G compassionate-use program. Results: From May
2005 to August 2006, 15 pts were enrolled. Median age 65 years (50-85); males=
14 pts (93%); never/former smokers= 4/10 pts (26/67%); adenocarcinoma= 10 pts
(67%); PS 0/1= 5/10 pts (33/67%); in 2 pts (13%) E was administered as
first-line therapy, 8 pts (53%) received 2 prior lines of chemotherapy (CT) and
3 pts (20%) received CT between E and G. One patient (7%) had a partial
response (PR) and 5 pts (33%) had disease stabilization (SD) with E; with G no
PR and 6 SD (40%) were obtained. Five out of 6 RP/SD pts with E, had SD with G;
8 out of 9 PD pts with E, had PD with G; 1 SD patient with E, progressed with G
and 1 vice versa. TTP in RP/SD pts was 7.2 and 3.4 months for E and G
respectively; in PD pts TTP was 1.7 and 1.6 for E and G respectively. Conclusions:
Our data suggest that there is a benefit with G in pts who had RP/SD with E and
that is associated with a good TTP. Conversely G is not recommended in pts that
immediately progressed after E. Moreover these results support the rationale of
treating PD pts with an EGFR TKI with another one; it may be worthwhile to
collect more data on E.

<op> </op>

<op> </op>

在治疗晚期非小细胞肺癌( NSCLC ) ,Tarceva治疗进展后用IRESSA治疗结果


子类:非小细胞肺癌类<op></op>

:肺癌会议: 2007 asco届年会打印机友好电子邮件<op></op>

文章摘要:
18 138

引文<op></op>

:临床肿瘤学杂志, 

2007 asco届年会诉讼第一部分25卷,第 18S系列( 6月20补编) , 2007年: 18 138

作者: F. Grossi, A. Brianti, C. Defferrari, M. Loprevite, G.
Catania, P. Pronzato

摘要<op></op>

:背景:两个病例报告描述了针对IRESSA失败后TARCEVA的效果(Garfield DH, J Clin Oncol 2005 ) ,或 TARCEVA失败后IRESSA的效果。(Choong
NW et al, 临床实用肿瘤2006年) 对
晚期非小细胞肺癌的患者. 另外, 有限的经验,在5病例表明TARCEVA不能有效正进行IRESSA治疗的患者，
((Viswanathan A et al, ,肺癌2005 ) . 

此项研究的目的是评价，对晚期非小细胞肺癌TARCEVA治疗
失败后，用IRESSA的效果和疾病进展时间( TTP )，<op></op>

方法:

病人得到150毫克/天TARCEVA治疗，之后病情进展( PD ).

病人收到250毫克/天的IRESSA治疗，试验被停止了，由于2006年8月TARCEVA被批准在意大利使用和随之而来的禁止IRESSA的慈善使用. 结果<op></op>

从2005年5月至2006年8月，15个病人注册试验. 年龄中位数65岁( 1950年至1985年) ; =男性14例( 93% ) ; 从不/从前吸烟者=4 / 10例(67分之26% ) ;腺癌10例( 67%
) ;

S 0 / 1 = 5 / 10例(67分之33% )
; 在2例中(占13% )TARCEVA被作为第一线治疗,
8例病人(
53% ) 以前得到2个化疗( CT ) ，3例( 20%
) , 在TARCEVA和IRESSA之间接受CT，接受TARCEVA治疗后，
其中一名病人(
7% ) 部分缓解( PR ) , 5例( 33%
)疾病稳定，接受IRESSA治疗后，没人部分缓解(

R)
，和6个稳定(SD)(
40% ) ，6个接受TARCEVA治疗后获得部分缓解或稳定的，接受IRESSA治疗后，5个是稳定， 9个接受TARCEVA治疗后进展的病人中，8人接受IRESSA治疗后仍进展，1个TARCEVA稳定，IRESSA进展，一个TARCEVA进展，但IRESSA是稳定，部分有效(RP)
和稳定(SD病人的TTP，TARCEVA和IRESSA分别是7.2和3.4个月; 进展病人(PD)的TTP，TARCEVA和IRESSA分别是1.7和1.6个月。<op></op>

 结论: 我们的资料显示, 对那些对TARCEVA是部分缓解(PR)或稳定的(SD)
的病人，，同时有与良好的TTP，IRESSA是有好益的。. 反之，TARCEVA后立即进展的病人，不推荐IRESSA。此外，这些研究结果支持基本理由--治疗进展的病人使用这种或那种EGFR
TKI; 也许值得收集更多的关于TARCEVA的数据<op></op>

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易瑞沙 耐药后的解决方案，请大家都来找出路

易瑞沙耐药后的解决方案，请大家都来找出路