Harvard Medical School, Clinical Director Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Cancer Chemother Pharmacol. 2011 Jan;67 Suppl 1:S45-50. doi: 10.1007/s00280-010-1527-2. Epub 2010 Dec 8.
The management of patients with gastrointestinal stromal tumor (GIST) has markedly advanced over the past 10 years. Imatinib has exceptional activity in controlling gastrointestinal stromal tumor (GIST) due to inhibition of the constitutively active conformation of KIT and PDGFRA which is found in the majority of patients with GIST. Although some patients may experience prolonged disease control while on imatinib, most patients will develop imatinib resistance within 2-3 years on therapy. A recent retrospective analysis demonstrated a relationship between imatinib plasma levels and progression-free survival in patients with advanced GIST. Plasma imatinib levels in this study were unrelated to the daily administered dose of imatinib. A prospective trial is underway in order to evaluate whether modification of imatinib dose to achieve a target imatinib plasma level will impact patient outcome when compared to standard imatinib dosing in GIST ( http://www.clinicaltrials.gov , NCT01031628). This review will explore the current available data on the relationship between imatinib plasma levels, response to treatment, and other prognositic factors as well as discuss the implications of this data for possible future therapeutic approaches.
过去 10 年来,胃肠道间质瘤(GIST)患者的管理取得了显著进展。伊马替尼通过抑制大多数 GIST 患者中存在的 KIT 和 PDGFRA 的组成性激活构象,对胃肠道间质瘤(GIST)具有特殊的活性。尽管一些患者在接受伊马替尼治疗时可能会经历疾病的长期控制,但大多数患者在治疗 2-3 年内会出现伊马替尼耐药。最近的一项回顾性分析表明,晚期 GIST 患者的伊马替尼血浆水平与无进展生存期之间存在相关性。本研究中的伊马替尼血浆水平与伊马替尼的每日给药剂量无关。目前正在进行一项前瞻性试验,以评估与标准剂量的伊马替尼相比,通过调整伊马替尼剂量以达到目标伊马替尼血浆水平是否会影响 GIST 患者的预后(http://www.clinicaltrials.gov,NCT01031628)。这篇综述将探讨目前关于伊马替尼血浆水平与治疗反应和其他预后因素之间的关系的现有数据,并讨论这些数据对未来可能的治疗方法的影响。