Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma
Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma
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DOI：
10.1200/jco.2006.06.6514
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发表时间：
2007-05-01
影响因子：
45.3
通讯作者：
Grossman, Stuart A.
中科院分区：
文献类型：
--
作者：
Nabors, L. Burt;Mikkelsen, Tom;Grossman, Stuart A.
这项多机构的I期试验旨在确定复发性恶性胶质瘤患者的最大耐受量(EMD 121974)，并评价其在磁共振成像中的应用。治疗周期为4周。治疗相关剂量限制性毒性(DLT)定义为任何3级或4级非血液毒性或任何持续时间的4级血液毒性。结果51例患者纳入6个队列，剂量分别为120、240、360、480、600、1,200、1,800和2,400 mg/m(2)，每周两次静脉滴注。3名患者进展较早，毒性评估无法评估。血栓形成1例(120 mg/m(2))，4级关节骨痛1例(480 mg/m(2))，血小板减少1例(600 mg/m(2))，厌食、低血糖、低钠血症1例(800 mg/m(2))。未达到MTD。2例完全缓解，3例部分缓解，4例病情稳定。灌注MRI显示，治疗16周后，肿瘤相对脑血流量(RCBF)的变化与血药浓度-时间曲线下面积之间存在显著相关性。结论Cilengiide对2400 mg/m(2)剂量耐受性良好，在I期试验中出现持久的完全和部分反应，临床反应与rCBF变化有关。
PurposeThis multi-institutional phase I trial was designed to determine the maximum-tolerated dose (MTD) of cilengitide (EMD 121974) and to evaluate the use of perfusion magnetic resonance imaging (MRI) in patients with recurrent malignant glioma.Patients and MethodsPatients received cilengitide twice weekly on a continuous basis. A treatment cycle was defined as 4 weeks. Treatment-related dose-limiting toxicity (DLT) was defined as any grade 3 or 4 nonhematologic toxicity or grade 4 hematologic toxicity of any duration.ResultsA total of 51 patients were enrolled in cohorts of six patients to doses of 120, 240, 360, 480, 600, 1,200, 1,800, and 2,400 mg/m(2) administered as a twice weekly intravenous infusion. Three patients progressed early and were inevaluable for toxicity assessment. The DLTs observed were one thrombosis ( 120 mg/m(2)), one grade 4 joint and bone pain ( 480 mg/m(2)), one thrombocytopenia (600 mg/m(2)) and one anorexia, hypoglycemia, and hyponatremia ( 800 mg/m(2)). The MTD was not reached. Two patients demonstrated complete response, three patients had partial response, and four patients had stable disease. Perfusion MRI revealed a significant relationship between the change in tumor relative cerebral blood flow (rCBF) from baseline and area under the plasma concentration versus time curve after 16 weeks of therapy.ConclusionCilengitide is well tolerated to doses of 2,400 mg/m(2), durable complete and partial responses were seen in this phase I study, and clinical response appears related to rCBF changes.