做凡人 发表于 2013-8-24 00:51:10

靶向治疗后的高剂量白介素治疗似乎效果更好

本帖最后由 做凡人 于 2013-8-24 01:04 编辑

这里有篇文章,有兴趣的可以读一下:
http://meetinglibrary.asco.org/content/89632-116

Background: High-Dose Interleukin-2 (HD IL2) remains a good option for treatment of metastatic renal cancer. As a first-line treatment, in carefully selected patients, it can produce high rates of response ( OR 50%; CR 25%) (Shablak A et al., J Immunotherapy 2011, 34(1):107-122). Its use after targeted therapies is controversial and there are reports of increased toxicity, particularly an increased incidence of cardiovascular toxicity (and possibly a reduced response rate (Cho DC et al., J Immunotherapy 2009, 32(2):181-520). However, there is potential to use it either in patients who have failed treatment with targeted therapy or as a consolidation therapy after successful treatment with a targeted agent. Methods: Here we present the outcomes of 16 patients treated with first-line immunotherapy with HD-IL2 after targeted therapy: of these 8 had been treated after failure of 1-3 lines of targeted therapy and 8 have been treated as consolidation after initial response to sunitinib. The histological characteristics of the tumours all fitted into the “favourable” group as defined previously by us and all had high levels of expression of CAIX (> 80%). All had ECOG PS 0/1, a satisfactory baseline stress echo, an interval of at least 8 weeks from last dose of targeted agent to start of HD-IL2 and at most 2 organs of disease. Results: Toxicity is indistinguishable from that of patients without prior treatment and no patient needed inotropic support or admission to intensive care. The number of doses given per cycle was also similar to that in unpretreated patients. Overall the response rates are excellent – with 9/13 evaluable patients having RECIST defined response and 6/13 having a complete remission. To date none of the patients in complete remission have realpsed but follow up is relatively short with the longest being 24 months. The responses have been particularly striking following treatment with mTor inhibitors. Conclusions: Overall, HD IL2 can be given safely in carefully selected patients after targeted therapies. It appears to be effective as a salvage therapy and potentially as a consolidation therapy. Updated results will be presented.

背景:高剂量白介素是转移性肾细胞癌的一个有效治疗办法。作为一线治疗,在认真选择的病人中,可以达到很高的有效率 (OR:50%,CR:25%)在靶向治疗之后使用白介素治疗是有争议的,有增加毒性尤其是心脏毒性的报道。然而仍然有潜力作为一线靶向治疗失败的选择或是作为治疗成功后的巩固。在这里我们介绍16个靶向治疗后用高剂量白介素治疗的资料。其中8个1-3线靶向治疗失败,另外八个舒尼替尼刚刚起效。病人的属性显示会有比较大的可能性对免疫治疗起效。(CAIX (> 80%)我不知道是啥。。)在开始治疗前他们停止靶向治疗至少八周,最多两个器官有病变。观察到的毒性和没有进行靶向治疗的病人无显著差异,剂量也没有区别。OR很惊人,13个可评估病人中,9个有反应,6个肿瘤完全消退。目前这六人都没有复发(目前还没有追踪很久,最长的24个月)。在mtor抑制剂之后的反应率尤其的好。结论:高剂量白介素治疗在靶向治疗之后仍旧适合而且有效。

当然还是小范围的实验,但是至少证明了即使靶向治疗之后,高剂量白介素还是可行的。但是身体功能要维持的比较好,因为副作用比较大。

做凡人 发表于 2013-8-24 05:50:04


http://www.ncbi.nlm.nih.gov/pubmed/20393025
找到了,有篇报道说CAIX高表达跟高剂量白介素成功概率相关
大意: 47个肾透明细胞癌病人,CR和PR只有3人(6%)和15人(32%)。 但CAIX为负的病人没有人对治疗有反应。

Abstract
Aim: The objectives of this study were to evaluate treatment responses to high-dose interleukin-2 (HD IL-2) in patients with metastatic renal cell carcinoma (mRCC) and assess correlation between responses and prognostic factors, such as histology, site of metastatic disease, prior treatment, prior nephrectomy, and carbonic anhydrase IX (CAIX) expression.
PATIENTS AND METHODS:
A retrospective analysis was performed on all mRCC patients treated with HD IL-2 between 1996 and 2006 at the University of Minnesota Medical Center in Minneapolis, Minnesota, USA. A cycle of HD IL-2 consisted of 600,000 U/kg given once every 8 hours for 14 doses. Cycles were repeated until disease progression or intolerable toxicities developed. CAIX expression and staining intensity were evaluated on available primary tumor tissue.
RESULTS:
Forty-seven patients with mRCC were identified. Of the 107 cycles of therapy that were given, 97.1% of patients received only two cycles of therapy. Complete response and partial response were seen in 3 (6%) and 15 (32%) patients, respectively. The overall disease control rate was 42.6%. The longest durable CR was 72 months and the shortest was 45 months. The median time to disease progression in patients with a CR or PR was 12 months. Patients with a Memorial Sloan-Kettering Cancer Center prognostic score of '1' were two times more likely to progress after two cycles than patients with a score of '0'. No response was observed in patients whose tumors were negative for CAIX by immunoperoxidase staining.
CONCLUSION:
HD IL-2 is a reasonable option for first-line therapy for selected patients with mRCC. Patients with tumors negative for CAIX may not benefit from HD IL-2 therapy. Further research is necessary to define patients with a higher likelihood of disease response to this therapy.

飞雪鸢 发表于 2013-8-24 18:54:04

高剂量是多高的剂量呢

常春藤 发表于 2013-8-25 07:02:08

靶向之后身体整体机能受损的情况下承受白介素之副作用,是很可怕的。如果用,必定要在医院医师的严密监控下实施。

好英雄老大 发表于 2013-8-25 19:44:24

都已经被折磨得很了,还能耐受高剂量的人又有多少?想想都可怕,万一遇到并发症怎么办?

stilllx 发表于 2013-8-29 00:26:00

适用于年轻体格好的人,最好还是靶向药前。博一把。

jove9999 发表于 2013-9-28 22:50:02

我吃了一年半的靶向药,然后做了伽马刀,休息了三个月了,能做白介素吗

leeefeng 发表于 2013-9-29 14:13:48

索坦服用了3年半了,这次检查有耐药迹象,目前身体状况尚可,不知国内哪家医院可以做这个?
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