Xiao-Tang Kong1, Nhung T Nguyen2, Yoon J Choi2, Guicheng Zhang3, HuyTram N Nguyen2, Emese Filka2, Stacey Green2, William H Yong4, Linda M Liau5, Richard M Green6, Tania Kaprealian7, Whitney B Pope8, P Leia Nghiemphu2, Timothy Cloughesy2, Andrew Lassman9, Albert Lai10. 1. Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; Department of Neurology, School of Medicine at University of California, Irvine, Irvine, California. 2. Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 3. School of Public Health, Xinxiang Medical University, Xinxiang, China, and Curtin University, Perth, Western Australia, Australia. 4. Department of Pathology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 5. Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 6. Kaiser Permanente Southern California, Los Angeles, California. 7. Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 8. Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 9. Department of Neurology, Columbia University, New York, New York. 10. Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. Electronic address: albertlai@mednet.ucla.edu.
Abstract
PURPOSE: To assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: Twenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6 weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, 11, 29, 32, 36, and 39. After RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, and 11 every 4 weeks. RESULTS: No unexpected adverse events occurred from the addition of bortezomib. The efficacy analysis showed a median progression-free survival (PFS) of 6.2 months (95% confidence interval [CI] 3.7-8.8), with promising PFS rates at ≥18 months compared with historical norms (25.0% at 18 and 24 months; 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI 6.7-31.4), with improved OS rates at ≥12 months (87.5% at 12, 50.0% at 24, 34.1% at 36-60 months) compared with the historical norms. The median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months (95% CI upper bound not reached) in the methylated and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients. CONCLUSIONS: The addition of bortezomib to current standard radiochemotherapy in newly diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising, with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.
PURPOSE: To assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: Twenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6 weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, 11, 29, 32, 36, and 39. After RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, and 11 every 4 weeks. RESULTS: No unexpected adverse events occurred from the addition of bortezomib. The efficacy analysis showed a median progression-free survival (PFS) of 6.2 months (95% confidence interval [CI] 3.7-8.8), with promising PFS rates at ≥18 months compared with historical norms (25.0% at 18 and 24 months; 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI 6.7-31.4), with improved OS rates at ≥12 months (87.5% at 12, 50.0% at 24, 34.1% at 36-60 months) compared with the historical norms. The median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months (95% CI upper bound not reached) in the methylated and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients. CONCLUSIONS: The addition of bortezomib to current standard radiochemotherapy in newly diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising, with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.
Authors: Patrick Y Wen; David R Macdonald; David A Reardon; Timothy F Cloughesy; A Gregory Sorensen; Evanthia Galanis; John Degroot; Wolfgang Wick; Mark R Gilbert; Andrew B Lassman; Christina Tsien; Tom Mikkelsen; Eric T Wong; Marc C Chamberlain; Roger Stupp; Kathleen R Lamborn; Michael A Vogelbaum; Martin J van den Bent; Susan M Chang Journal: J Clin Oncol Date: 2010-03-15 Impact factor: 44.544
Authors: Markus Bredel; Denise M Scholtens; Ajay K Yadav; Angel A Alvarez; Jaclyn J Renfrow; James P Chandler; Irene L Y Yu; Maria S Carro; Fangping Dai; Michael J Tagge; Roberto Ferrarese; Claudia Bredel; Heidi S Phillips; Paul J Lukac; Pierre A Robe; Astrid Weyerbrock; Hannes Vogel; Steven Dubner; Bret Mobley; Xiaolin He; Adrienne C Scheck; Branimir I Sikic; Kenneth D Aldape; Arnab Chakravarti; Griffith R Harsh Journal: N Engl J Med Date: 2010-12-22 Impact factor: 91.245
Authors: Philippe Moreau; Halyna Pylypenko; Sebastian Grosicki; Ievgenii Karamanesht; Xavier Leleu; Maria Grishunina; Grigoriy Rekhtman; Zvenyslava Masliak; Tadeusz Robak; Anna Shubina; Bertrand Arnulf; Martin Kropff; James Cavet; Dixie-Lee Esseltine; Huaibao Feng; Suzette Girgis; Helgi van de Velde; William Deraedt; Jean-Luc Harousseau Journal: Lancet Oncol Date: 2011-04-18 Impact factor: 41.316
Authors: Thomas Unterkircher; Silvia Cristofanon; Sri Hari Krishna Vellanki; Lisa Nonnenmacher; Georg Karpel-Massler; Christian Rainer Wirtz; Klaus-Michael Debatin; Simone Fulda Journal: Clin Cancer Res Date: 2011-04-27 Impact factor: 12.531
Authors: Olivier L Chinot; Wolfgang Wick; Warren Mason; Roger Henriksson; Frank Saran; Ryo Nishikawa; Antoine F Carpentier; Khe Hoang-Xuan; Petr Kavan; Dana Cernea; Alba A Brandes; Magalie Hilton; Lauren Abrey; Timothy Cloughesy Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: Mark R Gilbert; James J Dignam; Terri S Armstrong; Jeffrey S Wefel; Deborah T Blumenthal; Michael A Vogelbaum; Howard Colman; Arnab Chakravarti; Stephanie Pugh; Minhee Won; Robert Jeraj; Paul D Brown; Kurt A Jaeckle; David Schiff; Volker W Stieber; David G Brachman; Maria Werner-Wasik; Ivo W Tremont-Lukats; Erik P Sulman; Kenneth D Aldape; Walter J Curran; Minesh P Mehta Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: Daniela A Bota; Daniela Alexandru; Stephen T Keir; Darell Bigner; James Vredenburgh; Henry S Friedman Journal: J Neurosurg Date: 2013-10-04 Impact factor: 5.115
Authors: L F F Bittencourt; G L Negreiros-Lima; L P Sousa; A G Silva; I B S Souza; R I M A Ribeiro; M F Dutra; R F Silva; A C F Dias; F M Soriani; W K Martins; L S Barcelos Journal: J Neurooncol Date: 2019-08-07 Impact factor: 4.130
Authors: Md Yousuf Ali; Claudia R Oliva; Abu Shadat M Noman; Bryan G Allen; Prabhat C Goswami; Yousef Zakharia; Varun Monga; Douglas R Spitz; John M Buatti; Corinne E Griguer Journal: Cancers (Basel) Date: 2020-09-03 Impact factor: 6.639