Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

Abstract

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis Type 2(NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment.Dosing, demographic and adverse event(CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications.Eighty patients (48 male:32female), median age 24.5 years (range 11-66years), were followed for a median of 32.7 months (range 12.0-60.2months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24%) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5%) had proteinuria. Of 36 patients followed for 36 months, 78% were free from hypertension and 86% were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be predictors of development of hypertension with dose of 7.5mg/kg three weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described.Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.Introduction:

Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children

“…However, the long‐term effects of the medication, which appears to require continued dosing to keep the papilloma under control, is not yet known, and there is little information about the best protocol to use because of the lack of clinical trials. Some insight might come from the use of systemic bevacizumab as a maintenance therapy for neurofibromatosis 2, where it is used as a nonsurgical modality for skull base schwannomas . More data may come from the treatment of Rendu‐Osler‐Weber disease, where lower doses of systemic bevacizumab are currently being used to treat refractory bleeding .…”

“…Some insight might come from the use of systemic bevacizumab as a maintenance therapy for neurofibromatosis 2, where it is used as a nonsurgical modality for skull base schwannomas. 10 More data may come from the treatment of Rendu-Osler-Weber disease, where lower doses of systemic bevacizumab are currently being used to treat refractory bleeding. 11,12 Even with the limitations of this study, we report the use of systemic bevacizumab in two children without major complications and with a positive effect on respiratory symptoms during a follow-up of 4 years and 19 months, respectively.…”

Trends in phenotype in the English paediatric neurofibromatosis type 2 cohort stratified by genetic severity

“…23,24,[26][27][28][29] Those affected mildly, although suffering hearing loss, often live a full lifespan, work and reproduce. 34,35 Other agents including Everolimus have been tried but evidence on efficacy and safety is limited. 30 Management aims to maintain function and slow progression 3,31,32 but is complicated due to fear of radiation induced malignancy, 33 neurosurgical morbidity and Bevacizumab induced hypertension and proteinuria.…”

“…30 Management aims to maintain function and slow progression 3,31,32 but is complicated due to fear of radiation induced malignancy, 33 neurosurgical morbidity and Bevacizumab induced hypertension and proteinuria. 34,35 Other agents including Everolimus have been tried but evidence on efficacy and safety is limited. 36 Natural history NF2 data utilising current management is important, to inform management options.…”

Effect of bevacizumab against cystic components of brain tumors

“…Recent reports showed that BEV decreased the cysts' size of vestibular schwannoma, a representative tumor of extra-axial brain tumor, in neurofibromatosis type 2 patients. 7,8 However, there has been no report about BEV effect against cysts of intra-axial brain tumor including high grade glioma. In this study, we focused on the cystic components of intra-axial brain tumors.…”