| General information |
| Database: | DB00631 |
| Objective: | They evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, openlabel, noncomparative trial. |
| Authors: | Friedman HS, et al |
| Title: | Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19720927 |
| Trial Design |
| Clinical Trial Id: | NCT00345163 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Bevacizumab alone and + irinotecan |
| Study Type: | a phase II, multicenter, openlabel, noncomparative trial |
| Key Patients Feature: | Eligible patients had histologically confirmed glioblastoma in first orsecond relapse and had disease progression confirmed by magnetic resonanceimaging (MRI) 14 days before the first study treatment. Contrastenhancing, bidimensionally measurable disease was required. Patients hadbeen treated with standard radiotherapy and had received TMZ. Other keyinclusion criteria were Karnofsky performance status (KPS) 70%; life expectancy greater than 12 weeks; and adequate hematologic (ie, plateletcount 100, 000/ L, absolute neutrophil count 1, 500/ L), hepatic, andrenal function. Patients taking corticosteroids were required to be on a stableor decreasing dose for 5 or fetheyr days before baseline MRI. Therapeuticsystemic anticoagulation with low molecular weight heparin or warfarinwas allowed |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Bevacizumab alone VS combination with irinotecan |
| Treatment Info: | patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) (with or without concomitant enzymeinducing antiepileptic drugs, respectively) once every 2 weeks. |
| Primary End Point: | 6month progression free survival and objective response rate |
| Secondary End Point: | safety and overall survival |
| Patients Number: | 167 |
| Trial Results |
| DLT_MTD: | Of the patients treated with bevacizumab alone orbevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade 3 adverseevents, the most common of which were hypertension (8.3%) and convulsion (6.0%) in thebevacizumabalone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in thebevacizumabplusirinotecan group. |
| Objective Response Rate: | The estimated 6month PFS rates were 42.6% (97.5% CI, 29.6%to 55.5%) in the BV group and 50.3% (97.5% CI, 36.8% to 63.9%) inthe BV CPT11 group (Fig 2), and these exceeded the 15% rateassumed for salvage chemotherapy and CPT11 alone (P .0001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In the bevacizumabalone and the bevacizumabplusirinotecan groups, estimated 6month progression free survival rates were 42.6% and 50.3%, respectively |
| Median OS A vs. C: | In the bevacizumabalone and the bevacizumabplusirinotecan groups, median overall survival times were 9.2 months and 8.7 months, respectively. |
| Adverse Event(agent arm): | Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade 3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumabalone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumabplusirinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumabalone group (grade 1) and in three patients (3.8%) patients in the bevacizumabplusirinotecan group (grades 1, 2, and 4, respectively). |
| Conclusions: | Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma. |