爸爸去了天国, 终有一天我们会再次相聚

爸爸的女儿

哎, 有的时候真是很无奈的.  国家无法提供好的医疗条件物质条件给我们的父母, 所以我们这些做子女的只能努力承担, 大家都不容易, 压力无时无刻不存在.

爱的力量

原帖由 爸爸的女儿 于 2010-1-13 22:44 发表
今天，坐最早的直通车去了香港，先赶去中环邵医生的诊所买了下两次的阿瓦斯汀，然后去尖沙咀和湾仔公干，回到广州9点多了。邵医生好像把我和安安搞混了，说记得我是帮“老豆”（爸）买药，又说我爸以前用过力比泰，又 ...

Lily姐 我是全程讲普通话的哦，难道你也是讲普通话的。下次我们要是一起去，不是把他弄晕。

爸爸的女儿

好啊, 下次一起去.  我讲粤话, 不过广东人可以大致听出来我不是本地人.

爸爸的女儿

文献介绍，有人 用IRESSA无效后，用 TARCEVA有效(详见所付英文文摘)


ournal of Clinical Oncology, Vol 23, No 30 (October 20), 2005: pp. 7738-7740
© 2005 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2005.02.4471


--------------------------------------------------------------------------------

DIAGNOSIS IN ONCOLOGY

Modern Treatment of Lung Cancer
CASE 2. Response to Erlotinib After Failure of Gefitinib in a Patient With Advanced Non–Small-Cell Lung Carcinoma
David H. Garfield

Department of Medicine, University of Colorado Health Sciences Center, Aurora, CO

An 80-year-old white man presented with a 1-month history of cough and right-sided, nonpleuritic, anterior chest wall pain. Chest x-ray and computed tomography (CT) scans in May 2004 demonstrated bilateral upper lobe masses, larger on the right (8.5 cm) than the left side, with invasion of a right rib anteriorly. Performance status (PS) was 1. Medical history was pertinent for 40 to 60 pack-years of smoking until 30 years prior. His father, mother, and sister all were said to have died of lung cancer. CT-guided fine-needle aspiration (FNA) in May 2004 showed cells compatible with NSCLC, cell type not specified. In June, treatment was started with carboplatin/paclitaxel and zoledronic acid. He received four cycles, and had a brief, partial response (PR) manifested by less cough, reduced anterior chest pain, and an improved chest x-ray appearance. However, by August, disease had progressed in the same thoracic sites, and in September, he was found to have a single, 8-mm brain metastasis. "He received radiation to the rib and whole brain and was started on gefitinib, 250 mg/d. He had neither rash nor diarrhea and had no response in the chest. He was then given two courses of Alimta in November to December, again without response." At that time, PS was 3 and he was, therefore, transferred from home to nursing home in December. An anterior-posterior (AP) chest x-ray in early January showed a large, right upper lobe (RUL) mass, with 1 to 2 additional masses inferiorly, as well as smaller left upper lobe (LUL) masses (Fig 1, see three arrows, LUL masses not visible). "Early in January 2005, erlotinib, 150 mg/d, was started. Within 1 week, he developed rash and diarrhea, had disappearance of his chest pain, but now had a PS of 4. "Erlotinib was held for 1 week until toxicity improved, and was restarted at 150 mg, every other day. By mid-March 2005, the only toxicity was mild rash on the dorsum of his hands. PS was 2. AP chest x-ray showed a significant decrease in the size of the RUL mass and virtual disappearance of the inferior lesions on the right. Further decrease was noted at the end of April 2005, after almost 4 months of erlotinib. (Fig 2, see 2 arrows), and further decrease was noted one month later. However, 2 months later, there was slight growth of the RUL mass, and the LUL mass had reappeared, though he remained at PS2. Erlotinib was increased to 150 mg/d. His rash briefly worsened but then receded without treatment. Two months later, an AP chest x-ray showed that the two masses had stabilized.

[ 本帖最后由 爸爸的女儿 于 2010-1-25 15:32 编辑 ]

爸爸的女儿

Erlotinib Helps in Lung Cancer after Gefitinib Failure
By David Douglas

NEW YORK JUL 05, 2007 (Reuters Health) - Acquired resistance to a particular epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in patients with non-small-cell lung cancer may be overcome by use of a different tyrosine kinase inhibitor, according to Korean researchers.

As senior investigator Joo Hang Kim told Reuters Health, "Strategies for EGFR-targeted cancer therapies include small molecule EGFR inhibitors such as gefitinib (Iressa) or erlotinib (Tarceva). Although gefitinib showed dramatic responses in some patients, almost all patients ultimately experienced disease progression. Currently, there are no further treatment options for these patients."

Dr. Kim and colleagues at Yonsei University College of Medicine, Seoul, sought to determine whether a switch in therapy might help. The team studied 21 patients with advanced non-small-cell lung cancer who had progressed after gefitinib treatment and were then treated with standard doses of erlotinib.

The objective response rate was 9.5%, and 29% of patients had a response or stable disease, the team reports in the June 20th issue of the Journal of Clinical Oncology. The median time to progression was 60 days and the median overall survival was 158 days. Higher efficacy was observed in patients with wild-type EGFR who had stable disease on gefitinib.

"Our results are surprising," continued Dr. Kim, "because both gefitinib and erlotinib share the same mechanism of EGFR blockade and may be cross-resistant. Our results clearly imply that acquired resistance to an EGFR inhibitor can be overcome by a different EGFR inhibitor."

The investigators also emphasize "personalized and tailored lung cancer therapy based on molecular profiling in the era of targeted agents."

[ 本帖最后由 爸爸的女儿 于 2010-1-25 15:37 编辑 ]

爸爸的女儿

2009厄洛替尼（特罗凯）POST-ASCO 专家对话(2009-09-28 21:28:39)
标签：2009 厄洛替尼 特罗凯 asco 教育  分类：胸部肿瘤
2009年7月10～12日，由美国临床肿瘤学会（ASCO）和中国抗癌协会临床肿瘤学协作专业委员会（CSCO）联合举办的2009年ASCO年会精粹（Best of ASCO 2009）会议在青岛隆重举行，来自全国的400余位肿瘤学专家莅临会议。在该会的卫星会和其后的厄洛替尼（特罗凯）研讨会中，多位国内外肿瘤学专家全面总结了厄洛替尼在ASCO 2009年会肺癌领域中公布的重要进展。在此谨整理会议部分精彩内容，以飨读者。

    维持治疗

    意大利Humanitas临床研究所费德里科·卡普佐（Federico Cappuzzo，SATURN研究主要研究者）
     传统的晚期非小细胞肺癌（NSCLC）治疗采取“一线化疗→等待与观察→疾病进展后进行二线治疗”的模式，但一线含铂双药化疗因具有累积毒性而仅能给药4～6周期，另一方面有很高比例的患者在疾病进展后因症状和体力状态的迅速恶化而无法接受二线治疗。在这种背景下，一线化疗后立即以有效药物进行持续治疗的维持治疗模式应运而生，其目的在于延缓疾病进展和症状恶化，使患者保持较好的体力状态以耐受二线治疗，最终实现总生存（OS）的延长。理想的维持治疗药物除可有效延缓疾病进展外，还应具有良好的耐受性，使患者有机会从一线治疗的毒性中得以恢复，并且不应对生活质量带来不利影响。近年来公布的维持治疗研究大体可分为三类，分别应用二线化疗药、单抗类靶向药和表皮生长因子受体酪氨酸蛋白激酶抑制剂（EGFR-TKI）进行。

[ 本帖最后由 爸爸的女儿 于 2010-1-27 20:45 编辑 ]

爸爸的女儿

作为常用的NSCLC二线化疗药物，多西他赛和培美曲塞已分别被尝试用于维持治疗。在费迪亚斯（Fidias）等人于2007年公布的研究中，一线化疗疾病无进展的晚期NSCLC接受随机分组，研究组患者立即应用多西他赛进行维持化疗，对照组在疾病进展后应用多西他赛作二线治疗，结果显示维持治疗较二线治疗的无进展生存（PFS）有显著延长，但OS无显著差异。JMEN研究在一线化疗后给予培美曲塞维持治疗或安慰剂，根据贝拉尼（Belani）等于2009年ASCO年会更新的生存数据，与安慰剂组相比培美曲塞维持治疗组PFS显著延长2.0个月，OS显著延长2.8个月，证实维持治疗模式确实可能带来生存获益。亚组分析显示，培美曲塞维持治疗可显著改善非鳞癌患者的生存期，但未能给鳞癌患者带来获益，亚裔患者接受培美曲塞维持治疗的获益也不甚明确[风险比（HR）=1.05]。此外JMEN研究中安慰剂组患者仅有19%在二线应用了培美曲塞，其维持治疗是否优于二线治疗尚待进一步证实。该研究一线化疗方案中不包括培美曲塞方案，一线应用培美曲塞的患者是否仍能从该药维持治疗中获益也值得探讨。

    以厄洛替尼为代表的EGFR-TKI通过阻断EGFR信号传导通路、抑制癌细胞存活而发挥抗肿瘤作用。基础研究曾表明，由化疗药物引起的细胞周期阻滞和致凋亡作用，可被后续应用的厄洛替尼所增强，由此可以设想，一线化疗后以厄洛替尼进行维持治疗有可能改善疗效。

[ 本帖最后由 爸爸的女儿 于 2010-1-27 20:48 编辑 ]

爸爸的女儿

全球多中心随机双盲对照研究SATURN研究旨在探索EGFR-TKI维持治疗疗效与安全性，共纳入889例一线化疗后疾病未进展的晚期NSCLC患者，随机分组后给予厄洛替尼150 mg/d维持治疗或安慰剂，直至疾病进展。结果厄洛替尼维持治疗显著改善了患者的PFS，将疾病进展风险显著降低了29%（图1），其中EGFR免疫组化（IHC）阳性患者疾病进展风险降低31%。亚组分析进一步揭示，厄洛替尼维持治疗带来的PFS获益具有广泛性，无论患者年龄、种族、病理类型和吸烟史如何，均可从厄洛替尼维持治疗中显著获益，先前被认为是EGFR-TKI非优势人群的鳞癌患者在接受厄洛替尼维持治疗后，疾病进展风险亦显著降低24%（图2）。在分子标志物分析中，EGFR突变型患者接受厄洛替尼维持治疗后，疾病进展风险大幅度降低90%，而即使是EGFR野生型患者也可经厄洛替尼维持治疗显著降低22%的疾病进展风险。
    患者生活质量和安全性是衡量维持治疗合理性的重要关注点。在SATURN研究中，厄洛替尼维持治疗显著延迟了疼痛症状的出现，对其他各生活质量指标也无不利影响。在维持治疗组中发生率超过10%的不良反应仅有皮疹和腹泻，但达到3～4级的比例很低。

    SATURN研究与其他维持治疗研究值得进行比较。在日本患者中进行的WJTOG0203研究对一线化疗后疾病未进展的晚期NSCLC患者给予吉非替尼维持治疗或安慰剂，结果维持治疗组PFS有显著延长，但OS未见显著获益。在该研究亚组分析中，仅有腺癌和吸烟患者可从吉非替尼维持治疗中显著获得生存益处。与SATURN研究相比，JMEN研究的基线特征有所不同，其中预后较好的亚裔和不吸烟患者的比例分别为32%和25.6%，高于SATURN研究中相应特征患者的比例（14%和18%），而预后较差的鳞癌患者比例低于SATURN研究（26.1%对38%）。此外，与厄洛替尼维持治疗不同的是，培美曲塞仅可改善非鳞癌患者的生存。SATURN研究中，厄洛替尼为具有较高治疗难度的患者群体带来了广泛的获益，其治疗价值值得肯定。


    图1 SATURN研究中厄洛替尼显著延长患者的PFS

    图2 厄洛替尼维持治疗可使各人口学和临床特征亚组患者显著获益

    厄洛替尼通过阻断EGFR信号传导通路，在抑制肿瘤生长的同时也降低碱性成纤维生长因子（bFGF）、血管内皮生长因子（VEGF）、转化生长因子α（TGFα）等促血管生成因子合成，因而可能与抗血管生成药物具有一定的协同和互补作用。ATLAS研究共纳入近800例在一线化疗+贝伐单抗治疗后疾病未进展的晚期NSCLC患者（绝大多数为非鳞癌），随机分组后给予贝伐单抗+厄洛替尼或贝伐单抗+安慰剂治疗，与SATURN研究相似的是，在维持治疗阶段加入厄洛替尼后疾病进展也有显著的降低（HR=0.72，P=0.0012），并且年龄、种族、性别、吸烟史、体力状态等基线特征和一线化疗方案的选择均可从厄洛替尼维持治疗中获益。

    基于SATURN、ATLAS和JMEN等维持治疗研究的结果，维持治疗可延缓肿瘤的进展，并很有可能延长患者的生存。维持治疗的决策应以个体化的思路进行，根据患者意愿（是否愿意放弃“治疗假期”、倾向接受口服或注射给药）、EGFR状态（表达、扩增和突变等）以及病理学类型等因素，决定是否采用维持治疗以及应用何种药物

[ 本帖最后由 爸爸的女儿 于 2010-1-27 20:59 编辑 ]