Medical treatment in neurofibromatosis type 2. Review of the literature and presentation of clinical reports.
The understanding of the molecular pathways underlying tumor development in neurofibromatosis type 2 (NF2) is increasing. Thus, repositioning drugs, drug therapies that are already clinically available for various cancers, appear potentially promising for NF2 patients. Based on preclinical data from in vitro or animal models, five different treatments have been proposed for selected NF2 cases. Evaluation of bevacizumab, a monoclonal antibody against VEGF has mainly been reported in retrospective studies; it has been reported to induce hearing improvement and tumor shrinkage in more than 50% of progressive vestibular schwannomas (VS). In our experience with 16 patients, bevacizumab is associated with an increase of median time to tumor progression of VS from 5.6 months before bevacizumab onset, to more than 29.3 months. The need for intravenous injections and long term adverse events (hypertension, proteinuria, hemorrhage) are the main drawbacks. Lapatinib seemed promising in a single phase II trial with a volumetric response observed in 4/17 patients and a hearing response in 4/13, but is not currently used in clinical practice. Erlotinib has not been associated with radiographic or hearing responses in a phase II trial. Everolimus has been evaluated in 3 phase II trials. Everolimus did not induced tumor shrinkage, but seems to be able to increase time to tumor progression in selected cases. Currently, bevacizumab is the only drug proposed to selected NF2 patients.
Service de neurochirurgie, hôpital Beaujon, assistance publique-hôpitaux de Paris, 92100 Clichy, France.
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Goutagny
Service de neurochirurgie, hôpital Pitié-Salpêtrière, assistance publique-hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Université Pierre-et-Marie-Curie, faculté de médecine, 75013 Paris, France; Institut national de la santé et de la recherche médicale, U1127, institut cerveau moelle, 75013 Paris, France. Electronic address: michel.kalamarides@psl.aphp.fr.
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Kalamarides
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D005260:Female; D006309:Hearing / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D016518:Neurofibromatosis 2 / Q000188:drug therapy* / Q000601:surgery; D009464:Neuroma, Acoustic / Q000188:drug therapy* / Q000601:surgery; D012189:Retrospective Studies; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
Angiogenesis inhibitor; EGFR; MTOR; NF2; Neurofibromatosis type 2; Vestibular schwannoma