A F Cardona1,2,3, L Rojas4,5, B Wills6,7, A Ruiz-Patiño6,5, L Abril6, F Hakim8,9, E Jiménez8,9, N Useche8,10, S Bermúdez8,10, J A Mejía8,9, J F Ramón8,9, H Carranza11,6, C Vargas14, J Otero6, P Archila6, J Rodríguez6, J Rodríguez6, J Behaine8, D González8, J Jacobo8, H Cifuentes12, O Feo12, P Penagos12,13, D Pineda14, L Ricaurte6, L E Pino15, C Vargas14, J C Marquez14, M I Mantilla14, L D Ortiz16, C Balaña17, R Rosell17, Z L Zatarain-Barrón18, O Arrieta18. 1. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Calle 116 No. 9-72, c. 318, Bogotá, Colombia. a_cardonaz@yahoo.com. 2. Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia. a_cardonaz@yahoo.com. 3. Institute of Neuroscience, Universidad El Bosque, Bogotá, Colombia. a_cardonaz@yahoo.com. 4. Clinical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá, Colombia. 5. Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia. 6. Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia. 7. Internal Medicine Department, Johns Hopkins University, Baltimore, MD, USA. 8. Institute of Neuroscience, Universidad El Bosque, Bogotá, Colombia. 9. Neurosurgery Department, Fundación Santa Fe de Bogotá, Bogotá, Colombia. 10. Division of Neuro-radiology, Radiology Department, Fundación Santa Fe de Bogotá, Bogotá, Colombia. 11. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Calle 116 No. 9-72, c. 318, Bogotá, Colombia. 12. Neurosurgery Department, Clínica del Country, Bogotá, Colombia. 13. Neurosurgery Department, National Cancer Institute (INC), Bogotá, Colombia. 14. Division of Neuro-radiology, Radiology Department, Clínica del Country, Bogotá, Colombia. 15. Clinical Oncology Department, Fundación Santa fe de Bogotá, Bogotá, Colombia. 16. Division of Neuro-Oncology, Clinical Oncology Department, Clínica de Las Américas, Medellín, Colombia. 17. Medical Oncology Department, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. 18. Instituto Nacional de Cancerología, México City, Mexico.
Abstract
PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.
PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.
Authors: Roger Stupp; Warren P Mason; Martin J van den Bent; Michael Weller; Barbara Fisher; Martin J B Taphoorn; Karl Belanger; Alba A Brandes; Christine Marosi; Ulrich Bogdahn; Jürgen Curschmann; Robert C Janzer; Samuel K Ludwin; Thierry Gorlia; Anouk Allgeier; Denis Lacombe; J Gregory Cairncross; Elizabeth Eisenhauer; René O Mirimanoff Journal: N Engl J Med Date: 2005-03-10 Impact factor: 91.245
Authors: Winward Choy; Daniel T Nagasawa; Andy Trang; Kimberly Thill; Marko Spasic; Isaac Yang Journal: Neurosurg Clin N Am Date: 2012-06-05 Impact factor: 2.509
Authors: Lale Erdem-Eraslan; Martin J van den Bent; Youri Hoogstrate; Hina Naz-Khan; Andrew Stubbs; Peter van der Spek; René Böttcher; Ya Gao; Maurice de Wit; Walter Taal; Hendrika M Oosterkamp; Annemiek Walenkamp; Laurens V Beerepoot; Monique C J Hanse; Jan Buter; Aafke H Honkoop; Bronno van der Holt; René M Vernhout; Peter A E Sillevis Smitt; Johan M Kros; Pim J French Journal: Cancer Res Date: 2016-01-13 Impact factor: 12.701
Authors: Henry S Friedman; Michael D Prados; Patrick Y Wen; Tom Mikkelsen; David Schiff; Lauren E Abrey; W K Alfred Yung; Nina Paleologos; Martin K Nicholas; Randy Jensen; James Vredenburgh; Jane Huang; Maoxia Zheng; Timothy Cloughesy Journal: J Clin Oncol Date: 2009-08-31 Impact factor: 44.544
Authors: Kathleen M Schmainda; Melissa A Prah; Helga Marques; Eunhee Kim; Daniel P Barboriak; Jerrold L Boxerman Journal: Neuro Oncol Date: 2021-02-25 Impact factor: 13.029