Desjardins Annick, Reardon David A, Herndon James E, Marcello Jennifer, Quinn Jennifer A, Rich Jeremy N, Sathornsumetee Sith, Gururangan Sridharan, Sampson John, Bailey Leighann, Bigner Darell D, Friedman Allan H, Friedman Henry S, Vredenburgh James J
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Clin Cancer Res. 2008 Nov 1;14(21):7068-73. doi: 10.1158/1078-0432.CCR-08-0260.
Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan for patients with recurrent grade 3 malignant glioma.
Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab (10 mg/kg) and irinotecan every 14 days, a second cohort (n=24) was treated with bevacizumab (15 mg/kg) every 3 weeks with irinotecan on days 1, 8, 22, and 29 of each 42-day cycle. For both cohorts, the dose of irinotecan was 340 mg/m(2) for patients on enzyme-inducing antiepileptic drugs (EIAED) and 125 mg/m(2) for patients not on EIAEDs. After each 6-week cycle, patients were evaluated with a physical examination and magnetic resonance imaging.
The 6-month progression-free survival was 55% (95% confidence interval, 36-70%). The 6-month overall survival was 79% (95% confidence interval, 61-89%). Twenty patients (61%) had at least a partial response. Outcome did not differ between the two treatment cohorts. Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient, and one patient who developed thrombotic thrombocytopenic purpura.
Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma.
虽然新诊断的世界卫生组织（WHO）3级恶性胶质瘤患者的预后比WHO 4级恶性胶质瘤患者更有利，但复发后的挽救治疗基本上仅提供姑息性益处。我们对贝伐单抗（一种血管内皮生长因子单克隆抗体）联合伊立替康用于复发性3级恶性胶质瘤患者进行了一项II期试验。
在最初一组9例接受每14天一次贝伐单抗（10mg/kg）和伊立替康治疗的患者中证明了足够的安全性后，第二组（n = 24）每3周接受一次贝伐单抗（15mg/kg）治疗，在每个42天周期的第1、8、22和29天给予伊立替康。对于两组患者，服用酶诱导抗癫痫药物（EIAED）的患者伊立替康剂量为340mg/m²，未服用EIAED的患者为125mg/m²。每6周周期后，对患者进行体格检查和磁共振成像评估。
6个月无进展生存率为55%（95%置信区间，36 - 70%）。6个月总生存率为79%（95%置信区间，61 - 89%）。20例患者（61%）至少有部分缓解。两个治疗组的结果无差异。严重不良事件不常见，包括1例患者发生中枢神经系统出血，1例患者发生血栓性血小板减少性紫癜。
贝伐单抗和伊立替康是一种对复发性WHO 3级恶性胶质瘤患者有效的治疗方案，毒性可接受。
