托泊替康(和美新)在肿瘤脑转移中的应用

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托泊替康(和美新)在肿瘤脑转移中的应用
来源：中国医学论坛报 作者：上海胸科医院肺内科 沈洁 浏览： 12 发布时间：2008年12月28日
   脑转移是指原发于身体其他部位的肿瘤细胞转入颅内,是恶性肿瘤治疗失败的常见原因之一。据统计,约10%~30%的癌症患者在病程中出现脑转移,但其中约2/3生前无症状。随着社会人口老龄化,癌症发病率增高,诊断技术的提高及患者生存期的延长,预计脑转移瘤的发病率将更高。据大宗病例尸检结果及临床资料,实体瘤脑转移患者的数量是原发性脑瘤的10倍,实体瘤脑转移以肺癌最多,占脑转移瘤的40%~60%,甚或高达70%以上,乳腺癌次于肺癌居第二位,约占6.7%~26%,此外较常见的原发癌为肾癌、黑色素瘤、消化道肿瘤和淋巴瘤等。

   

    肺癌脑转移 托泊替康治疗的总缓解率为33.33%~57%

     托泊替康(和美新)具备良好的中枢神经系统(CNS)穿透性,平均脑脊液(CSF)穿透率 ≥30%,血清蛋白结合率≤20%,给药30分钟后在CSF中达到峰浓度,因此认为托泊替康可自由通过血脑屏障(BBB)。此外,在CSF中可检测到较高水平的托泊替康及其代谢物。

     已有多项小规模研究评估了托泊替康治疗脑转移的效果。结果显示,托泊替康对新发脑转移,特别是铂类敏感的小细胞肺癌(SCLC)有明确疗效。阿尔迪佐尼(Ardizzoni)等报告,11例无症状脑转移肺癌患者予托泊替康治疗,7例脑转移病灶可评估者中,3例完全缓解(CR),1例部分缓解(PR)(均见于敏感型SCLC患者)。德皮埃尔(Depierre) 等报告,9例脑转移患者中,4例PR,1例CR(患者同时还接受放疗)。克费尔(Korfel)报告的一项Ⅱ期临床研究评价了托泊替康在30例存在症状性脑转移的复发性SCLC患者中的应用。疗效评价:CR 10%,PR 23%,疾病稳定(SD)27%; 全组疾病进展时间(TTP)为3.1个月(0.25~14.2个月),总生存期(OS)为 3.6个月(0.25~14.2个月);托泊替康有效者的TTP为 3.9个月(1.4~6.7个月),OS为5.9个月(1.4~7.9个月)。一项针对SCLC和非小细胞肺癌(NSCLC)患者(n=255)的回顾性研究显示,24例(22例 SCLC和2例 NSCLC)可评估疗效和毒性的患者中,4例CR者均为SCLC,8例PR者中7例为SCLC,1例为NSCLC。22例SCLC患者的 OS 为6.1个月(图)。

   

    乳腺癌脑转移 托泊替康疗效初显

     在针对乳腺癌脑转移方面,有一项多中心Ⅱ期临床研究对托泊替康的疗效及安全性进行了评价。

     该研究排除既往曾接受过放疗者,共纳入24例乳腺癌伴两个径线可测量的脑转移患者,这些患者既往曾接受过辅助化疗或姑息性化疗。用药剂量为托泊替康1.5 mg/(m2·d),连续5天,每3周一个疗程,中位疗程数为3(1~11),不允许同时接受放疗(骨的姑息性放疗除外)。

     结果显示,在16例可评估疗效患者中,1例CR,5例PR,5例SD,缓解和疾病稳定的中位时间分别为124天(35~151天)和45天(41~161天);中位生存期为6.25个月(1.25~13.2个月)。

   

     结论 综上所述,托泊替康具备良好的CNS穿透性,治疗肺癌脑转移可达到较高的缓解率,为肺癌脑转移患者带来了福音。同时,Ⅱ期临床研究已显示出托泊替康对乳腺癌脑转移的疗效。


图 托泊替康对肺癌脑转移患者的疗效

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http://www.zlyp.cn/clinic_app/7919.html

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拓扑替康治疗小细胞肺癌的系统评价(PDF)《中国循证医学杂志》[ISSN:1672-2531/CN:51-1656/R]期数: 2007年03期 页码: 189-203 栏目: 二次研究 出版日期: 2007-03-25
文章信息/Info
Title: Topotecan for Small Cell Lung Cancer: A Systematic Review
作者: 王晓珊1；吴泰相2*；侯梅1
1. 四川大学华西医院肿瘤中心（成都 610041）
2. 四川大学华西医院循证医学与临床流行病学中心（成都 610041）

Author(s): WANG Xiao-shan1；WU Tai-xiang2*；HOU Mei1
1. Clinical Oncology Center, West China Hospital, Sichuan University, Chengdu 610041, China;
2. Chinese Evidence-Based Medicine Center/INCLEN CERTC, West China Hospital, Sichuan University, Chengdu 610041, China
关键词: 拓扑替康; 小细胞肺癌; 治疗; 系统评价

Keywords: Topotecan;  Small cell lung cancer;  Treatment;  Systematic review
分类号: -
DOI: -
文献标识码: A
摘要: 目的　系统评价拓扑替康在小细胞肺癌治疗中的临床疗效和安全性, 一线及二线治疗中的地位, 不同给药方式的疗效及其毒副作用。
方法　采用Cochrane系统评价方法，检索Cochrane图书馆临床对照试验库、MEDLINE、EMbase、Cancerlit、CBM、CNKI和VIP等电子数据库，并辅以手工检索和附加检索。检索时间截至2006年。由2名评价者独立评价并交叉核对纳入研究质量，对同质研究采用RevMan 4.2.8软件进行Meta分析。
结果　共纳入14个研究，2 099例小细胞肺癌患者，所有研究均报道采用了随机方法，均未详细报道随机方案的隐藏情况及是否采用盲法。Meta分析结果表明，TP 方案（拓扑替康＋顺铂）与EP方案（足叶乙甙＋顺铂）的反应率相似 [OR 0.83, 95%CI (0.63,1.09)]，但具有相对高的致血小板下降的骨髓毒性；单药拓朴替康与CE方案（足叶乙甙＋卡铂）的反应率相似 [OR 0.59, 95%CI (0.22,1.60)]；TEP方案（拓扑替康＋足叶乙甙＋顺铂）与EP方案的反应率相似 [OR 1.37, 95%CI (0.82,2.28)]，TEP方案致化疗后重度白细胞下降、重度血小板下降、重度血红蛋白下降均高于EP方案；口服拓扑替康与静脉滴注拓扑替康的化疗后反应率 [OR 0.97, 95％CI (0.60,1.57)]、中位疾病进展期 [WMD –2.32, 95％CI ( –5.72, 1.09)]、中位生存期 [WMD –1.65, 95％CI (–7.13,3.83)] 相似，口服拓扑替康化疗后重度中性粒细胞下降明显低于静脉滴注拓扑替康。所有研究共报道了45例治疗相关性死亡。
结论　拓扑替康治疗小细胞肺癌有确切临床疗效，无论是单药还是与其他药物的联合用药均具有与当前一线经典方案相当的疗效，但具有相对高的致白细胞和血小板下降的骨髓毒性，已被认为是治疗化疗敏感的小细胞肺癌患者复发的二线推荐药物，但是作为一线用药仍然需要更多的实践来证实。但由于纳入的研究存在选择性偏倚和测量性偏倚的高度可能性，势必影响结果的论证强度，期待更多高质量的随机双盲对照试验提供高质量的证据。

Abstract: Objective　To evaluate the role of topotecan in the treatment of small cell lung cancer (SCLC).
Methods　Up to 2006, we searched The Cochrane Library, MEDLINE, EMbase, Cancerlit, CBM, CNKI and VIP. Handsearch and additional search were also conducted. The quality of included studies was evaluated and meta-analyses were performed for the results of homogeneous studies by RevMan 4.2.8 software.
Results　Fourteen studies involving 2 099 participants with SCLC were included. All included studies were adequate in reporting randomization, while inadequate in allocation concealment and blinding. Meta-analyses showed that the response rate of TP (topotecan + cisplatin) regimen had no significant difference compared with EP regimen (etoposide + cisplatin) with OR 0.83 and 95%CI 0.63 to 1.09, but myelo-suppression such as leucopenia and thrombopenia was more severe with TP regimen; the response rate of monotherapy with topotecan was similar with that of CE (carboplatin + etoposide) regimen with OR 0.59 and 95%CI 0.22 to 1.60; the response rate of TEP (topotecan + etoposide + cisplatin) regimen was comparable with that of EP regimen with OR 1.37 and 95%CI 0.82 to –2.28, but myelosuppression and anemia were more severe with TEP regimen; the response rate with OR 0.97 and 95％CI 0.60 to –1.57, median time to progression with WMD –2.32 and 95％CI –5.72 to 1.09 and median survival time with WMD –1.65 and 95％CI –7.13 to 3.83 of IV topotecan were similar to those of oral topotecan, while neutropenia was more severe with IV topotecan. Forty-five treatment-related deaths were reported in all included studies.
Conclusions　Topotecan is an effective agent for SCLC when used as monotherapy or in combined treatment, but myelosuppression such as leucopenia and thrombopenia was relatively severe. Although it has been recommended as a second-line agent for recurrence of sensitive SCLC, more clinical trials are needed to define its role in first-line treatment. Due to a high risk of selection bias and detection bias in included studies, the evidence is insufficient to determine the effect of topotecan. Further large-scale trials are required to define the role of topotecan in the treatment of SCLC.

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坚强小鱼

好像对非小细胞肺癌不敏感。

步行者

对非小细胞癌的研究怎么说呢
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