Bevacizumab monotherapy for temozolomide-refractory malignant glioma

Abstract

Background: To evaluate the efficacy and toxicity of bevacizumab (Bev) as a new agent for molecular targeted therapy to treat recurrent high-grade glioma after failure using temozolomide (TMZ). Materials and methods: Five patients (age range, 32-77; Karnofsky performance scale, 40-70) with recurrent high-grade glioma who experienced treatment failure with TMZ were treated with Bev monotherapy since August 2009 at Kyorin University Hospital upon approval of the Institutional Review Board. The tumors consisted of anaplastic astrocytoma (2 cases), primary glioblastoma (2 cases), and secondary glioblastoma (l case). Bev was intravenously administered at 10 mg/kg at an every 2-week interval. Response was evaluated by Macdonald criteria. Results: Bev therapy was performed as second line therapy in three cases, and as third in two cases. The number of Bev cycles in each case was 1, 4, 4, 7, and 17, respectively. The tumor progressed in two cases within 3 months after Bev therapy was initiated. In one case, the Bev treatment was terminated after one cycle because of aggravation of meningeal dissemination, and thus was considered not evaluable. The maximum reduction in each tumor volume was 100%, 65%, 56%, and 33%, respectively. One patient had a partial response (PR), and three had stable disease (SD), resulting in an overall response rate of 25%. After initiation of Bev therapy, radiographic findings were rapidly improved in four evaluable patients, as well as their neurological status including restoration of motor function in two cases. Three patients had died of disease progression. High-grade adverse events were not observed including cerebral hemorrhage. On diffusion-weighted MR imaging, the apparent diffusion coefficient (ADC) values of all tumors which responded to Bev were higher than 1,100 ×10-6 mm 2/sec, whereas tumors with an ADC value lower than 1,100 did not. Conclusions: Bev monotherapy was found to be active and safe to TMZ-refractory, recurrent high-grade gliomas and resulted in substantial reduction of tumor volume with partial symptom relief. The duration of response, however, may not be long enough. Tumors that responded to Bev tended to show high ADC values. These data suggest that Bev may be an important molecular targeted therapeutic agent against TMZ resistant gliomas, and clinical trials of Bev in both recurrent and newly-diagnosed glioblastoma are currently underway in Japan and world-wide.