Clin-Ongoing Clinical Trials

Abstract

INTRODUCTION: Bevacizumab has been reported to be an effective treatment for symptomatic radiation necrosis and to decrease focal edema around areas of radiation necrosis. We report our preliminary results and ongoing clinical trial of bevacizumab treatment for radiation necrosis. METHODS: Thirteen patients with symptomatic radiation necrosis were treated with bevacizumab. Radiation necrosis was diagnosed according to the patients' clinical courses, magnetic resonance images, and fluoridelabeled boronophenylalanine-positron emission tomography (F-BPA-PET). Lesion/normal (L/N) ratios less than 2.0 and 2.5 on F-BPA-PET were defined as absolute and relative indications for bevacizumab treatment, respectively. The patients were treated with bevacizumab at a dose of 5 mg/ kg every 2 weeks, 6 cycles in total. RESULTS: Two patients were excluded from analysis because of adverse events. Eleven patients underwent 3 to 6 cycles of bevacizumab treatment. The median rate of the reduction in peri-lesional edema was 65.5% (range: 2.0% to 81.0%). The Karnofsky performance status (KPS) improved in 6 patients after bevacizumab treatment, and in 5 patients the status did not change. The L/N ratio on F-BPA-PET (P ¼ 0.0084) and the improvement of KPS after bevacizumab (P ¼ 0.0228) were significantly associated with the reduction rate of peri-lesional edema after bevacizumab treatment. CONCLUSION: Bevacizumab is a very effective treatment for radiation necrosis, irrespective of the original tumor histology. F-BPA-PET could be useful for diagnosing radiation necrosis and for making the decision as to whether or not to treat symptomatic radiation necrosis with bevacizumab. The clinical trial "Intra-venous administration of bevacizumab for the treatment of radiation necrosis in the brain" has been approved as Investigational Medical Care System by the Japanese Ministry of Health, Labour and Welfare. This trial has been ongoing since April, 2011.

Recent Advances in the Clinical Targeting of Hedgehog/GLI Signaling in Cancer

“…Patients with recurrent glioblastoma multiforme, in a phase 2 trial, were randomized to pre-operative and post-operative vismodegib arm versus post-operative vismodegib arm, with the idea that Hh pathway inhibitors selectively target glioma cancer stem cells. Although a significant decrease in the number of CD133+ neurospheres was observed in pre-operative and post-operative vismodegib arm, vismodegib did not appear to be clinically active in recurrent glioblastoma multiforme [67].…”

Bevacizumab for the Treatment of Glioblastoma

“…52 Finally, the safety of bevacizumab combined with temozolomide in the standard chemo-irradiation schedule for GBM was assessed in the AVAGLIO phase III study. 54 This trial did not find new bevacizumabrelated complications. The most common adverse events in bevacizumab plus temozolomide arm were hypertension, proteinuria, bleeding problems and arterial thromboembolic events (see Table 3).…”

“…A radiologic central review assessed a median PFS of 4.3 months in placebo arm and 8.4 months in bevacizumab arm [stratified HR: 0.61 (95% CI: 0.53–0.71) P < 0.0001 (log-rank test)]. 54 At the interim analysis, the OS did not cross the threshold for significance, with 263 events in placebo arm and 254 in bevacizumab arm. Final OS data are expected in October 2013.…”

“…Moreover, there was also observed to be a significant delay in the need for steroids, and KPS scores of independency were maintained for longer in patients treated with bevacizumab. 54…”

“…It was reported that a number of patients with recurrent malignant glioma treated with bevacizumab developed a diffuse infiltrating disease at the time of progression, particularly those patients who demonstrated radiographic responses, 28 but an evaluation of progression patterns in patients included in the BRAIN study showed that most patients did not experience a change from baseline in radiographic characteristics of the disease. 66…”