Fadul Camilo E, Kingman Linda S, Meyer Louise P, Cole Bernard F, Eskey Clifford J, Rhodes C Harker, Roberts David W, Newton Herbert B, Pipas J Marc
Department of Medicine, Section of Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center Drive, One Medical Center Drive, Lebanon, NH 03756, USA.
J Neurooncol. 2008 Nov;90(2):229-35. doi: 10.1007/s11060-008-9655-9. Epub 2008 Jul 26.
Irinotecan is a cytotoxic agent with activity against gliomas. Thalidomide, an antiangiogenic agent, may play a role in the treatment of glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and irinotecan, we conducted a phase II trial in adults with newly-diagnosed or recurrent GBM.
Thalidomide was given at a dose of 100 mg/day, followed by dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 700 mg/m(2) for patients taking enzyme-inducing anticonvulsants and 350 mg/m(2) for all others. The primary endpoint was tumor response, assessed by MRI. Secondary endpoints were toxicity, progression-free survival, and overall survival.
Twenty-six patients with a median age of 55 years were enrolled, with fourteen evaluable for the primary outcome, although all patients were included for secondary endpoints. One patient (7%) exhibited a partial response after twelve cycles, and eleven patients (79%) had stable disease. The intention to treat group with recurrent disease included 16 patients who had a 6-month PFS of 19% (95% CI: 4-46%) and with newly-diagnosed disease included 10 patients who had a 6-month PFS of 40% (95% CI: 12-74%). Gastrointestinal (GI) toxicity was mild, but six patients (23%) experienced a venous thromboembolic complication. Two patients had Grade 4 treatment-related serious adverse events that required hospitalization. There were no treatment-related deaths.
The combination of irinotecan and thalidomide has limited activity against GBM. Mild GI toxicity was observed, but venous thromboembolic complications were common.
伊立替康是一种对胶质瘤具有活性的细胞毒性药物。沙利度胺作为一种抗血管生成药物，可能在多形性胶质母细胞瘤（GBM）的治疗中发挥作用。为评估沙利度胺与伊立替康联合用药的效果，我们对新诊断或复发的GBM成年患者进行了一项II期试验。
沙利度胺的给药剂量为100mg/天，随后每2周剂量递增100mg/天，目标剂量为400mg/天。伊立替康在每3周周期的第1天给药。服用酶诱导性抗惊厥药的患者伊立替康剂量为700mg/m²，其他所有患者为350mg/m²。主要终点为肿瘤反应，通过MRI评估。次要终点为毒性、无进展生存期和总生存期。
共纳入26例患者，中位年龄55岁，14例可评估主要结局，不过所有患者均纳入次要终点分析。1例患者（7%）在12个周期后出现部分缓解，11例患者（79%）病情稳定。复发疾病的意向性治疗组包括16例患者，其6个月无进展生存期为19%（95%CI：4 - 46%）；新诊断疾病组包括10例患者，其6个月无进展生存期为40%（95%CI：12 - 74%）。胃肠道（GI）毒性较轻，但6例患者（23%）出现静脉血栓栓塞并发症。2例患者发生4级治疗相关严重不良事件，需要住院治疗。无治疗相关死亡病例。
伊立替康与沙利度胺联合用药对GBM的活性有限。观察到轻度胃肠道毒性，但静脉血栓栓塞并发症较为常见。
