Bevacizumab for Progressive Vestibular Schwannoma in Neurofibromatosis Type 2

Plotkin, Scott R.; Merker, Vanessa L.; Halpin, Chris; Jennings, Dominique; McKenna, Michael J.; Harris, Gordon J.; Barker, Frederick G.

doi:10.1097/mao.0b013e31825e73f5

Cited by 209 publications

(149 citation statements)

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“…Hypertension and proteinuria are known adverse events associated with bevacizumab therapy in malignant disease [14] and in NF2 [3,15,4,6]. In addition, hypertension is more common in NF2 than in the general population.…”

Section: Introductionmentioning

confidence: 99%

“…The optimal timing and duration of treatment are yet to be identified. Longer breaks in treatment have been associated with tumour regrowth in some cases [3,6]. Therefore, once tumour growth has been controlled, UK practice has been to maintain tumour stability using a reduced dose intensity 'maintenance' regimen [6].…”

Section: Introductionmentioning

confidence: 99%

“…Bevacizumab is now an established treatment option for Neurofibromatosis type 2 (NF2) associated schwannomas in the UK, Europe and the United States, with over 100 people being treated in the UK alone for rapidly growing schwannomas [1][2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

et al. 2016

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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: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:

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

et al. 2016

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“…Plotkin and colleagues conducted a retrospective analysis of 10 patients with NF2 and bilateral schwannomas treated with bevacizumab (a monoclonal antibody that blocks the action of VEGF) showing shrinkage of the vestibular schwannomas in 9 of 10 patients. Updated data from this study showed that of 31 patients treated and followed up 57% showed hearing improvement and in 55% there was radiological response concerning the volume of the schwannomas 73 . Preclinical studies have shown that EGFR and VEGF signaling pathways are functionally linked, which could justify the design of future clinical trials with the combination of lapatinib and bevacizumab targeting vestibular schwannomas in NF2.…”

Section: Molecular Biology and Potential Treatmentsmentioning

confidence: 99%

Neurofibromatosis: part 2 – clinical management

Batista

Goloni-Bertollo

Costa

et al. 2015

Arq. Neuro-Psiquiatr.

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Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1.Keywords: neurofibromatosis, neurofibromatosis type 1, neurofibromatosis type 2, schwannomatosis, Legius syndrome. resumo A primeira parte desta diretriz abordou o diagnóstico diferencial das neurofibromatoses (NF): neurofibromatose do tipo 1 (NF1), neurofibromatose do tipo 2 (NF2) e schwannomatose (SCH). As NF compartilham algumas características, como a origem neural dos tumores e sinais cutâneos, e afetam cerca de 80 mil brasileiros. O aumento do conhecimento científico sobre as NF tem permitido melhor manejo clínico e redução da morbidade das complicações, resultando em melhor qualidade de vida para os pacientes com NF. A maioria dos médicos é capaz de realizar o diagnóstico das NF, mas a variedade de manifestações clínicas e a dificuldade de se prever o surgimento e a gravidade de complicações, torna o manejo da NF um desafio para o clínico e envolve diferentes especialistas para o tratamento adequado e aconselhamento genético, especialmente a NF2 e a SCH. O presente texto sugere algumas orientações para o acompanhamento dos portadores de NF, com ênfase na NF1.Palavras-chave: neurofibromatoses, neurofibromatose 1, neurofibromatose 2, schwannomatose, síndrome de Legius. 532Arq Neuropsiquiatr 2015;73(6): [531][532][533][534][535][536][537][538][539][540][541][542][543] Part 1 of this guideline addressed differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH) 1 . This second part aims to offer some practical suggestions on the clinical management of NF.NF shares some features, such as the genetic origin of the neural tumors, cutaneous manifestations, heterogeneous phenotype and unpredictable and usually progressive natural course. However, they differ in age of onset, progression of the symptoms and prognosis. Moreover, NF clinical presentation and severity vary among patients and even between twins carrying the same NF gene mutation 2 . The wide range of NF clinical manifestations and the difficulties to predict the onset or the severity of new features, consequences, o...

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“…In two retrospective studies, VEGF blockade with bevacizumab was followed by hearing improvement and tumor shrinkage in more than 50 % of progressive VS in NF2 [6][7][8]. Effect on meningiomas seems modest [9,10].…”

Section: Introductionmentioning

confidence: 99%

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

et al. 2015

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Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective singleinstitution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was [20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was [20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume C20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to [ 12 months. Hearing was stable under treatment. The safety of everolimus was manageable.To the memory of Beatrice Larroque, who died accidentally as this paper was written.Electronic supplementary material The online version of this article

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Bevacizumab for Progressive Vestibular Schwannoma in Neurofibromatosis Type 2

Cited by 209 publications

References 30 publications

Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

Neurofibromatosis: part 2 – clinical management

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

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