PURPOSE: Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS: Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS: Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION: High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.
PURPOSE:Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS: Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS: Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION: High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.
Authors: Tracy T Batchelor; Elizabeth R Gerstner; Kyrre E Emblem; Dan G Duda; Jayashree Kalpathy-Cramer; Matija Snuderl; Marek Ancukiewicz; Pavlina Polaskova; Marco C Pinho; Dominique Jennings; Scott R Plotkin; Andrew S Chi; April F Eichler; Jorg Dietrich; Fred H Hochberg; Christine Lu-Emerson; A John Iafrate; S Percy Ivy; Bruce R Rosen; Jay S Loeffler; Patrick Y Wen; A Greg Sorensen; Rakesh K Jain Journal: Proc Natl Acad Sci U S A Date: 2013-11-04 Impact factor: 11.205
Authors: Scott R Plotkin; Simone L Ardern-Holmes; Fred G Barker; Jaishri O Blakeley; D Gareth Evans; Rosalie E Ferner; Tessa A Hadlock; Chris Halpin Journal: Neurology Date: 2013-11-19 Impact factor: 9.910
Authors: Claire Forde; Andrew T King; Scott A Rutherford; Charlotte Hammerbeck-Ward; Simon K Lloyd; Simon R Freeman; Omar N Pathmanaban; Emma Stapleton; Owen M Thomas; Roger D Laitt; Stavros Stivaros; John-Paul Kilday; Grace Vassallo; Catherine McBain; Simon Kerrigan; Miriam J Smith; Martin G McCabe; Elaine F Harkness; D Gareth Evans Journal: Neuro Oncol Date: 2021-07-01 Impact factor: 12.300
Authors: Matthias A Karajannis; Audrey Mauguen; Ekrem Maloku; Qingwen Xu; Erin M Dunbar; Scott R Plotkin; Anna Yaffee; Shiyang Wang; J Thomas Roland; Chandranath Sen; Dimitris G Placantonakis; John G Golfinos; Jeffrey C Allen; Nicholas A Vitanza; Luis A Chiriboga; Robert J Schneider; Jingjing Deng; Thomas A Neubert; Judith D Goldberg; David Zagzag; Filippo G Giancotti; Jaishri O Blakeley Journal: Mol Cancer Ther Date: 2021-06-17 Impact factor: 6.261
Authors: Heather L Thompson; Ann Blanton; Barbara Franklin; Vanessa L Merker; Kevin H Franck; D Bradley Welling Journal: Neurology Date: 2021-07-06 Impact factor: 11.800
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