我父亲肺鳞癌的治疗贴(2014年3月1日驾鹤西去）

另外提示大家：BIBW 2992与食物同时服用会影响吸收，它溶解于pH1~6.8，因此不建议用肠溶胶囊。

另外上上周有病友推荐阿托伐他汀（Liptor，立普妥）代替辛伐他汀，我调查，立普妥的降血脂效果比辛伐他汀要强，但副作用大一倍。

越来越年轻，是不是你给吃什么激素类的吃多了？
0 j' }2 X- o* d: s* ^+ E年轻好啊。

老马 发表于 2012-8-10 20:16

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+ @& H' v& E) _我今天观察老爸，发现眉毛和胡子变黑了，新长的头发也是黑的。太奇怪了！@

不奇怪，我家老歌也是这样的.

有个问题：对于her2扩增的，拉帕替尼和阿法替尼效果都不错，拉帕的NSCLC二期临床有一例肿瘤缩小了51%，但对于her2突变的，拉帕效果不成，而阿法替尼有效果。

Lapatinib minimally effective for non-small-cell lung cancer
' t3 p3 s/ u  R7 ?MARCH 18, 2010

+ x0 i, F$ m4 [+ K  XNEW YORK (Reuters Health) - Although well tolerated, lapatinib is minimally effective as monotherapy for advanced or metastatic non-small-cell lung cancer (NSCLC), according to a report in the March 15th Clinical Cancer Research.

Lapatinib (GlaxoSmithKline) is a tyrosine kinase inhibitor of both epidermal growth factor receptor (EGFR) and HER2, the authors explain, and thus has theoretical advantages over inhibition of either EGFR or HER2 alone.
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Dr. Helen J. Ross, from Mayo Clinic, Scottsdale, Arizona, and colleagues evaluated the overall response rate to lapatinib in 131 patients with advanced or metastatic NSCLC. Sixty-five patients were randomized to lapatinib 1500 mg once daily and 66 to lapatinib 500 mg twice daily.
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. R, H$ V( ]7 j" c& _; }3 GWhen the study began, patients with any type of advanced or metastatic NSCLC were recruited ("non-targeted" population). However, when data from other studies began to show that EGFR inhibitors are particularly effective in patients with bronchioloalveolar carcinoma and in never-smokers with any histology of NSCLC, recruitment began to "target" such patients.

The targeted population included 24 patients in the 1500 mg/day group and 32 in the 500 mg twice daily group. The corresponding numbers in the non-targeted population were 41 and 34.
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At the interim analysis of the first 30 targeted patients to reach the initial response evaluation, the response rate was 0% in both treatment groups. In the non-targeted population, one patient in the 1500-mg group achieved a partial response.
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Overall, 31 of 131 patients (24%) had stable disease or better.
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Based on these findings, the study was stopped for reasons of futility, the investigators state.

$ O5 x$ W' N" Q; N  O: L6 AOverall survival in the targeted population was 15.2 months for the 1500-mg once-daily group and 13.9 months for the 500-mg twice-daily group, and in the nontargeted population, overall survival was 11.4 months for the 1500-mg once-daily group and 8.1 months for the 500-mg twice-daily group.

2 Y2 o% o- Q: Q: ?Median progression-free survival was 15.6 weeks (1500-mg once-daily) and 8.7 weeks (500-mg twice-daily) in the targeted population and 12.0 weeks (1500-mg once-daily) and 8.6 weeks (500-mg twice-daily) in the nontargeted population.

- L! V! ]0 W2 p4 I! h' [The incidence of adverse events considered to be related to study medication was 89% for 1500 mg once daily and 83% for 500 mg twice daily, but only 8% of patients in each group experienced serious adverse events related to study medication.
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Among 92 patients with tumor tissue available, 2 had mutations in EGFR and 1 had mutations in both EGFR and KRAS. None had mutations in HER2.
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& |& [  J/ P0 `' u. gOf 77 patients with sufficient DNA for gene copy evaluation, 5 (8.8%) had increased EGFR copy number and 2 (3.5%) had increased HER2 gene copy number.
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8 Y! m. |! W% [  JNone of the patients with EGFR mutations responded to lapatinib, and only 1 patient with HER2 amplification had an unconfirmed decrease of 51% in tumor measurement.
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"Lapatinib as a single agent at the doses studied seems to have minimal single-agent activity, at least as measured by response rates," the authors conclude, "although progression-free survival in the 1500-mg once-daily group was in the range that would be expected with first-line chemotherapy."
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8 n6 h% g+ k6 b/ H: i"Patients in this small study had a suggestion of disease stabilization with lapatinib," Dr. Ross said. "It would be of interest to examine it in the adjuvant setting after resection perhaps, after chemoradiotherapy perhaps or after up-front chemotherapy. It is possible that combination with other targeted agents, such as anti-angiogenic agents, might be useful."
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The study was sponsored by GlaxoSmithKline.

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Clinical Cancer Researchclincancerres.aacrjournals.org
" i- T1 Z- O4 f  k9 b$ iPublished OnlineFirst February 8, 2012; doi: 10.1158/1078-0432.CCR-11-2511
5 P5 x! [, s4 O: mClin Cancer Res April 1, 2012 18; 1947
6 C* W! V3 P( |  z# _Frequency of Driver Mutations in Lung Adenocarcinoma from Female Never-Smokers Varies with Histologic Subtypes and Age at Diagnosis
Yang Zhang1,3, Yihua Sun1,3, Yunjian Pan1,3, Chenguang Li1,3, Lei Shen2,3, Yuan Li2,3, Xiaoyang Luo1,3, Ting Ye1,3, Rui Wang1,3, Haichuan Hu1,3, Hang Li1,3, Lei Wang1,3, William Pao4, and Haiquan Chen1,3
* o; m2 l" |' j, h7 ]5 ^, o+ Author Affiliations
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Authors' Affiliations: Departments of 1Thoracic Surgery and 2Pathology, Fudan University Shanghai Cancer Center; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; and 4Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
Corresponding Author:
Haiquan Chen, Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China. Phone: 86-21-6417-5590; Fax: 86-21-6268-6511; E-mail: hqchen1@yahoo.com; and William Pao, Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232. Phone: 615-936-3524; Fax: 615-343-7602; E-mail: william.pao@vanderbilt.edu
Y. Zhang, Y. Sun, and Y. Pan contributed equally to this work and should be considered co-first authors.
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Abstract
+ t6 S  c! B/ i. x2 w. i; }& ~Purpose: Our previous study revealed that 90% [47 of 52; 95% confidence interval (CI), 0.79–0.96] of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma.
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8 F+ D' @  B# E( {5 w9 nExperimental Design: Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histologic subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathologic parameters according to mutational status of these genes.

Results: Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (P < 0.001), whereas patients harboring HER2 mutations were significantly younger (P = 0.036). Higher prevalence of KRAS (P = 0.028) and HER2 (P = 0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (P = 0.002). Multivariate analysis revealed that older age at diagnosis (P = 0.013) and acinar predominant subtype (P = 0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (P = 0.030) and IMA (P = 0.017). IMA (P = 0.006) and poor differentiation (P = 0.028) were independently associated with KRAS mutations.

Conclusions: The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histologic subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies. Clin Cancer Res; 18(7); 1947–53. &copy;2012 AACR.

Her2-Targeted Therapies in Non–Small Cell Lung Cancer
http://clincancerres.aacrjournals.org/content/12/14/4377s.full
Sensitivity to Her2-directed therapies is complex and involves the expression of not only Her2 but also other EGFR family members, their ligands, and molecules that influence pathway activity, such as insulin-like growth factor-1 receptor, PTEN, and p27. It is unclear whether agents targeting Her2 will prove successful in future clinical trials in a highly selected patient cohort, either with Her2 amplification or Her2 gene mutations. The frequency of Her2 mutations in NSCLC may be too low to justify a prospective clinical trial in this patient group. Nevertheless, the EGFR experience has taught us that responses can easily be diluted in an unselected cohort of patients.
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Certainly, trials to date have been insufficiently powered to determine whether NSCLC patients with Her2 gene amplification (rather than overexpression by immunohistochemistry) benefit from Her2-targeted therapies. The frequency of Her2 amplification (2-23%) in NSCLC and the widespread availability of Her2 FISH analysis may justify a final study of trastuzumab monotherapy in this patient population.

/ e/ v" s7 C* `& C. [5 U3 oThe role played by Her2 as the obligate heterodimerization partner for the other EGFR family members renders Her2 an attractive target irrespective of receptor overexpression. Arguably, the most exciting Her2 approach will prove to be combinatorial approaches using an EGFR tyrosine kinase inhibitor together with Her2 dimerization inhibitors (e.g., pertuzumab).
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Given the central part played by Her2 in receptor signaling, gene amplification witnessed in human malignancies, and the recent Her2 mutations documented in NSCLC, the failure of trastuzumab in clinical trials of NSCLC should not discourage further studies of these potentially important agents.

几种主要检测方法的比较— IHC、FISH、ELISA的区别？
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' ~' V6 r6 |+ W% z  Y a)IHC用特异的抗体检测HER2蛋白，其有以下特点： 高敏、快速， 在细胞或组织中精确定位过度表达蛋白， 新鲜冰冻或石蜡包埋切片均能应用。优点：试剂应用较少，设备较简单。缺点是福尔马林固定或石蜡包埋切片可使HER2检出率降低。HER2抗原在福尔马林固定或石蜡包埋切片中抗降低，这和以下因素有关：组织固定的时间和自然状态、组织处理的方法、石蜡包埋的温度、保存时间（特别未染色切片）、检测的抗体。
, i9 e8 K! X1 i  @" Vb)FISH测定HER2基因的扩增已被用于乳腺癌的诊断，它有以下特征：高敏， 通常采用福尔马林固定、石蜡包埋切片，固定、包埋切片中敏感性并不降低。但比IHC步骤复杂，需要一些较为特殊的设备，需要特异性和地高辛连接的HER2反义寡聚核苷酸，反义寡聚核苷酸和HER2结合存在于切片中，这可以通过针对于地高辛的免疫荧光素标记的抗体，用免疫荧光的方法测定。
7 g9 @( }4 j# T/ V5 i+ ~2 Rc)ELISA能用于新鲜肿瘤组织或血清的HER2蛋白的测定，其结果可能和IHC及FISH测定有区别。ELISA法检测血清HER2蛋白的终点与IHC/FISH不同：ELISA检测脱落循环受体，而后两者检测扩增基因/细胞蛋白。血清中的HER2蛋白是细胞HER2蛋白100-110kD的细胞外区。
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# J; q  v/ `  u) j+ O对于HER2状况作了IHC检测是否还要进行FISH检测？

a)IHC与FISH检测都可以比较准确的反映HER2状况，两者之间有较高的一致性。以百分比形式的IHC报告不能作为用药参考。罗氏提供的HER2检测手册中有检测标准流程和评分方法的详细介绍
b)IHC 3＋的患者与FISH＋的一致性达到89%，不同IHC 试剂检测的2＋的患者中有24%-53%的患者FISH＋，关键性临床试验数据显示赫赛汀对IHC 2+的患者仍然有效。
5 C: M+ b! o& A1 C2 [c)FISH检测从基因层面诊断HER2基因的扩增，可以更准确检测病人的HER2状况。目前国内也有1～2家中心可以进行此项检测复旦大学附属上海肿瘤医院病理科。
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想问下，为啥要做胸部伽玛刀放疗呢？
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