title: 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:32 female), median age 24.5 years (range 11-66 years), were followed for a median of 32.7 months (range 12.0-60.2 months). 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 independent predictors of development of hypertension with dose of 7.5 mg/kg 3 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.
authors: Nuffield Department of Neurosciences and NF2 Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.|University of New South Wales, Sydney, Australia.
authors: Katrina A
authors: 0000-0003-1075-8424
authors: KA
authors: Morris
authors: University of Westminster, London, UK.
authors: John F
authors: JF
authors: Golding
authors: John Radcliffe Hospital, Oxford Cancer Centre, The Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors: Claire
authors: C
authors: Blesing
authors: Genomic Medicine, Institute of Human Development, MAHSC, University of Manchester, St Mary's Hospital, Manchester, UK.
authors: D Gareth
authors: DG
authors: Evans
authors: Department of Neurology, Neurofibromatosis Service, Guy's & St Thomas' Hospital, Great Maze Pond, London, SE1 9RT, UK.
authors: Rosalie E
authors: RE
authors: Ferner
authors: Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Karen
authors: K
authors: Foweraker
authors: Department of Genetics and NF2 Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors: Dorothy
authors: D
authors: Halliday
authors: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors: Raj
authors: R
authors: Jena
authors: The Christie NHS Foundation Trust, Manchester, UK.
authors: Catherine
authors: C
authors: McBain
authors: Centre for Paediatric, Teenage and Young Adult Cancer, Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors: Martin G
authors: MG
authors: McCabe
authors: Department of Neurology, Neurofibromatosis Service, Guy's & St Thomas' Hospital, Great Maze Pond, London, SE1 9RT, UK.
authors: Angela
authors: A
authors: Swampillai
authors: John Radcliffe Hospital, Oxford Cancer Centre, The Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors: Nicola
authors: N
authors: Warner
authors: Department of Paediatric Oncology, The West Wing, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors: Shaun
authors: S
authors: Wilson
authors: Nuffield Department of Neurosciences and NF2 Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors: Allyson
authors: A
authors: Parry
authors: Department of Neurology, Neurofibromatosis Service, Guy's & St Thomas' Hospital, Great Maze Pond, London, SE1 9RT, UK. Shazia.Afridi@gstt.nhs.uk.
authors: Shazia K
authors: SK
authors: Afridi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects*; D000068258:Bevacizumab / Q000009:adverse effects*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000150:complications / Q000188:drug therapy*; D016518:Neurofibromatosis 2 / Q000150:complications / Q000188:drug therapy*; D012044:Regression Analysis; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab
keywords: Bevacizumab; Cardiac failure; Hypertension; Neurofibromatosis type 2; Proteinuria; Toxicity