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不知道有没有人发过，我看到有讨论这个药但是没见到关于肾癌的，如果有发过不好意思啊，连接在这里
http://www.asco.org/ASCOv2/Meeti ... mp;abstractID=95382
看到这个药是看了Chris Battle的博客 http://kidneycancerchronicles.com/author/chris/ 在这里也推荐一下。他很乐观，四年参加各种临床试验，不断地因为无效被踢出来，他写的总是很诙谐，医生担心他的病熬不过这个月都被他说得轻描淡写的，各种乐观向上，最新的几个提到了这个药。有个临床试验是关于肾癌但是要求骨转，他不符合得自己掏钱，最近一个写到他的肿瘤有缩小，自己四年的感慨，我真的边看边哭。癌症病人和家属都太不容易了，大家都要加油！好药越来越多！活着就有希望！
感觉比较有意义的是临床实验的人之前大多都吃过各种各样的靶向药，结果还不赖，貌似没有什么交叉耐药，网上找了一段大概的中文介绍。
Cabozantinib（ XL184）为针对MET 及VEGFR2 的靶向药物。有基础研究发现，抗血管生成靶向药物耐药可能与MET激活有关，通过抑制MET 通路可能能够克服抗VEGF 治疗所造成的获得性耐药。本届大会发言报告了一项XL184 用于治疗复发难治性晚期肾癌的临床研究，共入组25 例患者。这些患者既往接受过多种靶向药物治疗，给予口服XL184 140mgqd，同时联合罗格列酮治疗。客观有效率达28%，疾病控制率达80%，仅4% 的患者出现原发耐药治疗，大部分患者的肿瘤获得缩小，16 周的疾病控制率为72%，全部患者的中位PFS为14.7 个月，中位随访14.7 个月后中位总生存时间仍未达到。不良反应主要为疲乏、腹泻等，与其他靶向药物的不良反应类似。上述研究的结果取得如此令人惊喜的效果，可能有望进行晚期肾癌的一线药物治疗临床试验。
Efficacy of cabozantinib (XL184) in patients (pts) with metastatic, refractory renal cell carcinoma (RCC).
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Sub-category:
Kidney Cancer
Category:
Genitourinary Cancer
Meeting:
2012 ASCO Annual Meeting
Session Type and Session Title:
Oral Abstract Session, Genitourinary Cancer (Nonprostate)
Abstract No:
4504
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4504)
Author(s):
Toni K. Choueiri, Sumanta Kumar Pal, David F. McDermott, David A. Ramies, Stephanie Morrissey, Yihua Lee, Dale Miles, Jaymes Holland, Janice P. Dutcher; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA; City of Hope, Duarte, CA; Beth Israel Deaconess Medical Center, Boston, MA; Exelixis, South San Francisco, CA; Dana-Farber Cancer Institute, Boston, MA; St. Luke's-Roosevelt Hospital Center, New York, NY
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^) here and in the printed Proceedings.
Abstract Disclosures
Abstract:
Background: Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2 that is currently undergoing evaluation in several oncology indications. Renal cell carcinoma (RCC) was chosen as an indication in this drug-drug interaction (DDI) study based on involvement of the MET and VEGFR signaling pathways in this disease. The primary objective of this study is to determine the effect of cabo on single dose PK of the CYP2C8 substrate rosiglitazone (rosi). Anti-tumor activity was also evaluated. Methods: Eligible pts were required to have RCC with clear cell components with metastases, Karnofsky performance status of ≥70 and measurable disease by RECIST. Pts needed to have experienced PD following standard therapies. Cabo was given daily at a dose of 140 mg free base (equivalent to 175 mg salt form) starting at Day 2. Rosi (4 mg) was given Day 1 and Day 22 to complete PK assessment for DDI. Cabo was continued until PD. On Day 57 and every 8 weeks thereafter subjects underwent tumor assessments by mRECIST. Results: Enrollment is complete at 25 RCC pts; 17/25 (64%) RCC pts had received ≥ 2 prior agents; 13/25 (52%) with at least 1 VEGF pathway inhibitor and 1 mTOR inhibitor. The majority of pts were in an intermediate (21/25) or poor (3/25) prognostic category (1/25 in favorable category) per Heng et al (JCO, 2009, v27, p5794). ORR by mRECIST: 7/25 (28%). Disease control rate (PR + SD): 72% at 16 weeks; 19/21 (90%) pts with ≥1 post-baseline scan experienced tumor regression (range: 4 - 63% reduction in measurements). 10/25 (36%) pts remain on cabo. Median PFS is 14.7 months (95% CI: 7.3, upper limit not reached) with a median follow-up of 7.7 months. AEs ≥ Grade 3 severity: hypophosphatemia (36%), hyponatremia (20%), and fatigue (16%). PK data suggest that clinically relevant doses of cabo do not alter the Cmax or AUC0-24h of rosi, consistent with no inhibition of CYP2C8. Conclusions: Cabo demonstrates encouraging anti-tumor activity in heavily pretreated RCC pts with a toxicity profile similar to that of other VEGFR TKIs. PK data suggest no DDI between cabo and rosi (CYP2C8 substrate). |
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