| General information |
| Database: | DB00619 |
| Objective: | The authors performed a phase 2 trial of combined protracted daily temozolomide and biweekly bevacizumab for patients with recurrent glioblastoma who had previously received radiation therapy and temozolomide. |
| Authors: | Desjardins A, et al |
| Title: | Bevacizumab and daily temozolomide for recurrent glioblastoma. |
| Journal: | cancer |
| Year: | 2012 |
| PMID: | 21792866 |
| 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 and daily temozolomide |
| Study Type: | a phase II trial |
| Key Patients Feature: | istologicallydocumented GBM, had received prior daily temozolomide and radiation therapy followed by 5day temozolomide at some time before enrollment and had progressive, measurable disease documented on magnetic resonanceimaging (MRI). Patients also were required to have thefollowing measurements and conditions: a Karnofsky performance status 60%; adequate hematologic function(an absolute neutrophil count 1500/lL and a plateletcount >125, 000/mm3) and organ function (creatinine<1.5 mg/dL, aspartate aminotransferase and bilirubin<1.5 times the normal); at least 4 weeks from any majorsurgery or 1 week from minor surgery, including a stereotactic brain biopsy; at least 4 weeks from completion ofradiation therapy; absence of acute hemorrhage on MRI;and absence of progression on daily temozolomide. Therewas no limit to the number of previous disease progressions or treatment regimens. Previous exposure to or evenfailure on bevacizumab was allowed. Contraceptive measures were required for sexually active patients. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | 32 adult patients were enrolled. Patients received temozolomide 50 mg/m(2) daily and bevacizumab 10 mg/kg intravenously every 14 days. Patients underwent physical examination and brain magnetic resonance imaging every 8 weeks. |
| Primary End Point: | PFS, OS and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 32 |
| Trial Results |
| DLT_MTD: | Twopatients discontinued therapy secondary to toxicity (prolonged thrombocytopenia and grade 4 pancreatitis). Onepatient experienced grade 5 pneumonia. |
| Objective Response Rate: | The authors observed a 6month progression free survival (PFS) rate of 18.8% (95% confidenceinterval [CI], 7.6%33.7%) and a median PFS of 15.8 weeks. The median overall survival (OS) was 37 weeks, the 6month OS rate was 62.5% (95% CI, 43.5%76.7%), and the 12month OS rate was 31.3% (95% CI, 16.4%47.3%). Ninepatients (28%) had a radiographic response, and 7 patients (22%) had disease progression within the first 8 weeks oftreatment |
| Disease Control Rate: | 0.78 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 15.8 weeks. |
| Median OS A vs. C: | 37 weeks |
| Adverse Event(agent arm): | Grade 3 toxicities included 3 patients who experienced grade 3 fatigue and 7 patients each with a single symptom of diarrhea, dehydration, hemorrhoids, dyspnea, hypertension, colitis, and hyperglycemia. One patient experienced grade 5 pneumonia. |
| Conclusions: | The current study demonstrated that a regimen of combined daily temozolomide and biweekly bevacizumab had some activity and was well tolerated. Hotheyver, the results obtained in this study they were inferior to those observed in studies of bevacizumab monotherapy and of combined irinotecan and bevacizumab therapy. The current patient population was more heterogeneous and was pretreated more heavily than patients in previous studies. |