| General information |
| Database: | DB00622 |
| Objective: | To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. |
| Authors: | Vredenburgh JJ, et al |
| Title: | The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21531816 |
| 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: | 3 |
| Therapeutic Combination Content: | bevacizumab plus standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan |
| Study Type: | phase II trial |
| Key Patients Feature: | Seventyfive newly diagnosed glioblastoma patients wereenrolled in the trial and had received no therapy for theirtumor besides surgical resection. Patients had a Karnofskyperformance status (KPS) of 60% or greater and were 18years or older. Patients enrolled for a minimum of 2 weeksbut not more than 6 weeks from their last surgical procedure. Eligibility required adequate hematologic and organfunction. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5day temozolomide with bevacizumab and irinotecan every 14 days. |
| Primary End Point: | the proportion of patients alive 16 months |
| Secondary End Point: | NA |
| Patients Number: | 75 |
| Trial Results |
| DLT_MTD: | The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervoussystem hemorrhage, came off study during radiation therapy. Seventy patients started the postradiationtherapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity |
| Objective Response Rate: | The median overallsurvival was 21.2 months (95% CI: 17.2-25.4), and 65% of the patients were alive at 16 months (95% CI:53.4-74.9). The median progression free survival was 14.2 months (95% CI: 12-16). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 14.2 months (95% CI 12-16) |
| Median OS A vs. C: | 21.2 months (95% CI 17.2-25.4) |
| Adverse Event(agent arm): | Six patients (8%) developed grade 4 thrombocytopenia and an additional four patients (5%) developed grade 4 neutropenia. There were two toxic deaths, one from neutropenic sepsis and one from a pulmonary embolism. In addition, sixteen of the 70 patients (23%) that started adjuvant temozolomide, bevacizumab and irinotecan terminated protocol treatment for toxicity, including one botheyl peforation, likely attributable to the bevacizumab. |
| Conclusions: | The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results fromphase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established. |