Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation

Morris, Katrina; Golding, John F.; Axon, Patrick; Afridi, Shazia; Blesing, Claire; Ferner, Robin E; Halliday, Dorothy; Jena, R.; Pretorius, Pieter; Evans, D. Gareth; McCabe, Martin G.; Parry, Allyson

doi:10.1093/nop/npv065

Cited by 53 publications

(77 citation statements)

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“…The clinical records of 80 NF2 patients who commenced treatment with bevacizumab between August 2010 and November 2014 according to the UK national protocol were reviewed [6]. Bevacizumab treatment dose and the presence of any adverse events were recorded at each cycle of treatment alongside the need for any break in treatment.…”

Section: ) Study Cohortmentioning

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%

“…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%

“…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]. This approach has also been successfully used by another group when toxicities occur [1,7].…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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: ) Study Cohortmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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Current Management of Large Vestibular Schwannomas for NF2 Patients in a National Reference Center

et al. 2020

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Objective Recently, treatment decision making for large vestibular schwannomas (VS) in patients with neurofibromatosis type 2 (NF2) has become increasingly challenging due to the availability of multiple therapeutic options including surgery, bevacizumab (an anti‐VEGF), radiosurgery, and observation; and it often remains an arbitrary decision based on local practices without firm recommendations. Our objective is to discuss the multimodal treatment options for Koos IV VS in a national reference center for NF2. Study Design Single‐institution retrospective cohort study. Methods All NF2 patients with Koos IV VS who visited our center, the National Reference Center for NF2 Rare Disease in Pitié‐Salpétrière Hospital of Paris, between January 2016 and December 2018 were included. Clinical charts, radiology, operative reports, and audiograms were reviewed. Results Among 54 NF2 patients with Koos IV VS (mean maximum extrameatal diameter: 34 mm; range:17–62 mm), 27 were operated on for 28 VS; 21 were treated with bevacizumab; and six were observed. In the surgical group, VS resections were gross total, near‐total, subtotal, or partial in 32%, 25%, 32%, and 11%, respectively; and a good (House‐Brackmann grades I–II) facial nerve function was achieved in 81.5% at 1 year. Hearing was preserved in 14%, 78%, and 66% of the surgical (n = 7), bevacizumab (n = 9), and observation (n = 3) patients, respectively. Conclusion All therapeutic options, including surgery and/or bevacizumab and occasionally observation, should be proposed to NF2 patients with large VS in the setting of dedicated centers. A decision‐making tree is proposed for Koos IV VS management based on tumor evolution, hearing and clinical status of the patient, and contralateral VS size. Level of Evidence 4, case series study, historically controlled study Laryngoscope, 131:E98–E107, 2021

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Bevacizumab for NF2‐associated vestibular schwannomas of childhood and adolescence

Renzi

Michaeli

Salvador

et al. 2020

Pediatric Blood & Cancer

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Seventeen children at six institutions with neurofibromatosis type 2 (NF2)‐related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2‐associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.

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Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation

Cited by 53 publications

References 21 publications

Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

Current Management of Large Vestibular Schwannomas for NF2 Patients in a National Reference Center

Bevacizumab for NF2‐associated vestibular schwannomas of childhood and adolescence

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