Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort
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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.
KeywordsNeurofibromatosis type 2 Cardiac failure Bevacizumab Hypertension Proteinuria Toxicity
English Specialist NF2 Research Group members: Cambridge and Central: Patrick Axon, Neil Burnet, Neil Donnelly, Juliette Durie-Gair, Martin English, Nicola Folland, Fiona Harris, Frances Harris, David Heney, Anke Henseik, Sarah Jeffries, Richard Knight, Tamara Lamb, Robert Macfarlane, Richard Mannion, James Nicholson, Richard Price, Ella Rands, Paul Sanghera, Daniel Scoffings, Amy Taylor, James Tysome, London: Chris Hammond, Karine Lascelles, Charles Nduka, Terry Nunn, Rupert Obholzer, Shakeel Saeed, Adam Shaw, Nick Thomas, Suki Thomson, Daniel Walsh, Victoria Williams, Sue Wood, Manchester: Raji Anup, Chris Duff, Simon R Freeman, Emma Howie, Susan M Huson, Nicola Jarvis, Ian Kamaly-Asi, Mark Kellett, Andrew King, John-Paul Kilday, Simon K Lloyd, Connor Malluci, Deborah Mawman, Sam Mills, Martin O’Driscoll, Sonia Patel, Mary Perry, Scott A Rutherford, Vilka Scott-Kitching, Stavros M Stivaros, Owen Thomas, Grace Vassallo, Charlotte L Ward, Oxford and South West: Lucy Cogswell, Louise Dalton, Caroline Dodridge, John Elston, Henk Giele, C Oliver Hanemann, Wendy Howard, David Johnson, Richard Kerr, Avianna Laws, James Lee, Elle Mace, Anne May, Chris Milford, Pieter Pretorius, James Ramsden, Carolyn Redman.
Dr Morris: NIHR RCF grant from the University of Oxford (AC12/092).
Compliance with ethical standards
Conflict of interest
No conflicts of interests for any of the authors.
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