肿瘤治疗新技术 医术天地

  • 用微信扫描以下二维码

    更多移动资讯等着你

  • 抗癌故事

肿瘤治疗新技术

首页
/
最新疗法
/
抗癌故事
/
癌症论坛
/
抗癌头条
/
名医博客
/
肿瘤问答
/
医学文献
/
健康大数据
/

紫杉醇纳米制剂对I/II期的晚期胰腺癌临床治疗 025

楼主:倾城花音2017-03-21 05:21 只看楼主

马上注册,结交更多好友,享用更多功能,让你轻松玩转社区。

您需要 登录 才可以下载或查看,没有帐号?立即注册

x
导读:据研究发现胰腺癌细胞及周围基质表达有富含半胱氨酸的酸性分泌蛋白,该蛋白可被紫杉醇纳米制剂识别并结合,导致更多的紫杉醇作用于肿瘤细胞,诱导肿瘤细胞坏死。
          紫杉醇纳米制剂是有蛋白质包裹的紫杉醇,据研究发现胰腺癌细胞及周围基质表达有富含半胱氨酸的酸性分泌蛋白,该蛋白可被紫杉醇纳米制剂识别并结合,导致更多的紫杉醇作用于肿瘤细胞,诱导肿瘤细胞坏死。该药物于2005年由FDA批准用于治疗复发或对其他化疗抵抗的乳腺癌。
2009年ASCO报道的紫杉醇纳米制剂在胰腺癌中的I/II临床研究简介如下:63例晚期胰腺癌患者接受如下治疗:紫杉醇纳米制剂(nab-P100-150 mg/m2), 吉西他滨 (G 1000 mg/m2) 分别与D1、8、15天,每四周重复。 结果最常见的3/4度骨髓毒性为中性粒细胞减少症(>20%)1例患者在接受nab-P 150 mg/m2后因脓毒血症并致死。49例被评价患者中1例(2%)CR,12例(24%)PR,20例(41%)SD,中位生存期9月。35例患者被检测SPARC表达,其中 10例 (29%) SPARC+; 25 例(71%) SPARC-. 在被检测SPARC表达的患者中, 27例可评价疗效:SPARC+患者较SPARC- 患者有更高的反应率(75% VS 26%,P=0.03)。中位无疾病进展时间SPARC+/ SPARC-为4.8月/6.2月。45例CA199基线水平升高患者中,42例(93%)患者CA199水平下降>40%。由此可见,nab-p+G在晚期胰腺癌中耐受良好,且有一定抗瘤作用,值得Ⅲ期临床研究进一步证实。SPARC+者有更高反应率和无疾病进展生存期。
SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study.
Citation:J Clin Oncol 27:15s, 2009 (suppl; abstr 4525)
Author(s):
D. D. Von Hoff, R. Ramanathan, M. Borad, D. Laheru, L. Smith, T. Wood, R. Korn, N. Desai, J. Iglesias, M. Hidalgo; TGen, Scottsdale, AZ; Mayo Clinic, Scottsdale, AZ; Johns Hopkins, Baltimore, MD; South Texas Oncology and Hematology, San Antonio, TX; University of Alabama, Birmingham, AL; Scottsdale Medical Imaging, Scottsdale, AZ; Abraxis BioScience, Los Angeles, CA
Abstract:
Background: Pancreatic cancer cells and surrounding stroma are known to overexpress SPARC (secreted protein acid rich in cysteine), which is associated with poor clinical outcomes. nab-P, an albumin-bound nanoparticle form of paclitaxel increased tumor accumulation of paclitaxel through binding of albumin to SPARC. This disease specific phase 1 study was designed to evaluate the safety and efficacy of G + nab-P and the correlation of response with tumor SPARC and serum CA19-9 levels.
Methods: nab-P doses (100-150 mg/m2) + (G) (1000 mg/m2) were given on days 1, 8, and 15 of a 28-day cycle to pts with metastatic pancreatic adenocarcinoma and with no prior chemotherapy for their metastatic disease. Level 3 SPARC staining by immunohistochemistry was considered positive.
Results: 63 pts received treatment. The most common grade 3 and 4 adverse event that occurred in >20% of pts was neutropenia. Nine (18%) pts and 4 (8%) pts had a grade 3/4 event, respectively. Neuropathy was also observed. One combination-associated death due to sepsis occurred at the 150 mg/m2 nab-P level. Serial PET scans of 53 pts with outside adjudication to date showed 12 (23%) complete responses, 29 (55%) partial responses (PRs) and 4 (8%) stable disease (SD). By RECIST criteria, of the 49 pts evaluable to date, 1(2%) had CR, 12 (24%) had PR, and 20 (41%) had SD. The median survival was 9 months to date. SPARC data were available for 35 pts, of which 10 (29%) were SPARC+ and 25 (71%) were SPARC-. Of these, 27 pts had evaluable response data. Pts that were SPARC+ (8/27) were more likely to be responders (6/8, 75%) than pts who were SPARC- (5/19, 26%), P = 0.03, Fishers exact test. Median progression-free survival (PFS) increased from 4.8 months for SPARC- pts (22 pts) to 6.2 months for SPARC+ pts (9 pts); however, these data are still immature. Of 45 pts with elevated CA19-9 at baseline, 42 (93%) had maximum decrease of >40% with a median maximum decrease of 92%.
Conclusions: The combination of nab-P and G was generally well tolerated and had substantial enough antitumor activity in patients with pancreatic cancer to warrant a phase III clinical trial. SPARC+ status in these patients was associated with higher response rate and longer PFS.



上一篇:胰腺癌手术适应症
下一篇:FDA批准近年来首个治疗晚期胰腺癌药
使用“←” “→”快捷翻页
作者:游客
您需要登录后才可以回帖 登录 | 立即注册

请遵守医术天地社区公约言论规则,不得违反国家法律法规

猜你喜欢

  • 冷冻消融,在肾癌治疗中显优势

  • 基因检测有什么用途?基因检测有用吗?

  • 干细胞治疗——让盲人重建光明

  • 干细胞储存有必要吗?该如何存储?

    友情链接:
    复大官方网站
    -
    亚西亚健康网
    -
    重庆肛肠医院
    -
    名医博客
    -
    抗癌资讯

    sitemap|网站地图|手机版|

    医术天地 (琼B2-20040038-1)

       

    快速回复 返回顶部 返回列表