Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Curr Opin Oncol. 2010 Jul;22(4):336-41. doi: 10.1097/CCO.0b013e32833a6b8e.
Imatinib has exceptional activity in controlling gastrointestinal stromal tumor (GIST) due to inhibition of the constitutively active conformation of KIT and platelet-derived growth factor-alpha (PDGFRA), which is commonly seen in this tumor. This review explores the current available data on the correlation between imatinib plasma levels, response to treatment, and the mutational status of KIT and PDGFRA.
A recent retrospective analysis demonstrated a relationship between imatinib plasma levels and progression-free survival in patients with advanced GIST. Plasma imatinib levels were notably unrelated to the daily administered dose of imatinib in this small series. Prior phase III trials have demonstrated that dose escalation of imatinib may lead to increased disease control in a subset of patients with advanced GIST who progress on standard dose imatinib. Moreover, patients with GIST carrying an exon 9 mutation may benefit from higher doses of imatinib.
Current available data suggest a possible correlation between imatinib plasma level and progression-free survival in patients with advanced GIST. A prospective trial is underway to evaluate whether modification of imatinib dose to achieve a target imatinib plasma level will impact patient outcome when compared with standard imatinib dosing (www.clinicaltrials.gov, NCT01031628).
由于伊马替尼可抑制胃肠道间质瘤（GIST）中常见的 KIT 和血小板衍生生长因子-α（PDGFRA）的组成性激活构象，因此对 GIST 具有出色的治疗活性。本综述探讨了伊马替尼血药浓度与治疗反应以及 KIT 和 PDGFRA 突变状态之间相关性的现有数据。
最近的一项回顾性分析表明，晚期 GIST 患者的伊马替尼血药浓度与无进展生存期之间存在相关性。在这项小系列研究中，伊马替尼血药浓度与每日给予的伊马替尼剂量明显无关。先前的三期试验表明，伊马替尼剂量的增加可能会导致标准剂量伊马替尼治疗进展的一部分晚期 GIST 患者的疾病控制得到改善。此外，携带外显子 9 突变的 GIST 患者可能受益于更高剂量的伊马替尼。
目前的可用数据表明，晚期 GIST 患者的伊马替尼血药浓度与无进展生存期之间可能存在相关性。目前正在进行一项前瞻性试验，以评估与标准剂量伊马替尼相比，通过调整伊马替尼剂量以达到目标伊马替尼血药浓度是否会影响患者的结局（www.clinicaltrials.gov，NCT01031628）。
Zotero 插件