| General information |
| Database: | DB00634 |
| Objective: | The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. they performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. |
| Authors: | Vredenburgh JJ, et al |
| Title: | Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. |
| Journal: | J Clin Oncol. |
| Year: | 2007 |
| PMID: | 17947719 |
| Trial Design |
| Clinical Trial Id: | NA |
| 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 plus irinotecan |
| Study Type: | phase II trial |
| Key Patients Feature: | patients were at least 19 years of age and had histologically proven GBMfor which they had received radiation therapy and temozolomide. All hadexperienced tumor progression, had measurable disease magnetic resonanceimaging (MRI), and had recovered from their prior treatment. A minimum of6 weeks was required from prior intracranial surgery, and a minimum of 4weeks after radiation and other chemotherapeutic agents, unless there wasevidence of tumor progression. The patients had to have an absolute neutrophil count more than 1, 500 L, a hematocrit more than 29%, and a plateletcount more than 125, 000 L. The patients also had to have a serum creatinineless than 1.5 mg/dL, bilirubin less than 1.5 mg/dL, and serum AST less than1.5 theupperlimitofnormal. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks.VS The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. |
| Treatment Info: | patients received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzymeinducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. |
| Primary End Point: | 6month progression free survival;OS;response;toxicity |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The 6month progression free survival among all 35 patients was 46% (95% CI, 32% to 66%). The6month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95%CI, 39% to 74%) had at least a partial response |
| Disease Control Rate: | 0.57 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 24 weeks (95% CI, 18 to 36 weeks). |
| Median OS A vs. C: | 42 weeks (95% CI, 35 to 60 weeks). |
| Adverse Event(agent arm): | One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). |
| Conclusions: | Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity. |