| General information |
| Database: | DB00607 |
| Objective: | he optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. they performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. |
| Authors: | Soffietti R, et al |
| Title: | Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of NeuroOncology). |
| Journal: | J Neurooncol |
| Year: | 2014 |
| PMID: | 24293233 |
| 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 fotemustine |
| Study Type: | a multicenter, single arm, open label, phase IIstudy |
| Key Patients Feature: | ageC18 years; Karnofsky performance status (KPS) score C60;histological diagnosis of glioblastoma at original surgery orat reoperation; first progression after radiotherapy and concomitant/adjuvant temozolomide; measurable disease onenhanced MRI (C1 cm) within 1 week prior to treatment;stable corticosteroid dose for C7 days before baseline MRI;adequate hematologic, hepatic and renal function: hematocrit[29 %; absolute neutrophil count (ANC) C1, 000 lL;platelets count C100, 000 lL; serum aspartate aminotranferase, bilirubin and creatinine1.5 times normal At least3 months between completion of radiotherapy and at least1 month between reoperation and enrollment were required |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The treatment consisted of an inductionphase with bevacizumab at 10 mg/kg intravenously on day 1 and 15 and fotemustine at 75 mg/m2 intravenously on day 1 and day 8, followed after an interval of 3 weeks by a maintenancephase with bevacizumab at 10 mg/kg and fotemustine at 75 mg/m2 every 3 weeks until tumor progression, unacceptable toxicity or withdrawal of consent. |
| Primary End Point: | 6month progression free survival (PFS) |
| Secondary End Point: | overall survival (OS), response rate and toxicity. |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Twentyeight patients (52%) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60%). |
| Disease Control Rate: | 0.89 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.2 months (95 % CI 3.8-6.6) |
| Median OS A vs. C: | 9.1 months (95 % CI 7.3-10.3) |
| Adverse Event(agent arm): | Most patients experienced grade 1 or 2 toxicities. Grade 3 toxicities were predominantly hematologic, including neutropenia in 7 patients (13 %) and thrombocytopenia in 5 patients (9 %). Other grade 3 toxicities included wound dehiscence in 3 patients (5.5 %), fatigue and deep venous thrombosis in 2 patients (4 %), and hypertension and hemorrhage (61) in 1 patient (1.8 %). Grade 4 toxicities included pulmonary embolism in 2 patients (4 %), and hypertension with reversible posterior encephalopathy, stroke, neutropenia and thrombocytopenia in 1 patient, respectively. |
| Conclusions: | This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs. |