Efficacy and safety of bevacizumab for the treatment of glioblastoma (Review)

Yu,Zhiyun; Zhao,Gang; Zhang,Zhonghua; Li,Yunqian; Chen,Yong; Wang,Nan; Zhao,Zhongying; Xie,Guifang

doi:10.3892/etm.2015.2947

Efficacy and safety of bevacizumab for the treatment of glioblastoma (Review)

Authors:
- Zhiyun Yu
- Gang Zhao
- Zhonghua Zhang
- Yunqian Li
- Yong Chen
- Nan Wang
- Zhongying Zhao
- Guifang Xie
View Affiliations

Affiliations: Department of Neurosurgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurosurgery, Siping Central People's Hospital, Siping, Jilin 136000, P.R. China, Department of Obstetrics and Gynecology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: December 16, 2015 https://doi.org/10.3892/etm.2015.2947
Pages: 371-380

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glioblastoma (GBM) is the most common and devastating primary malignant intracranial tumor in adults. The current first‑line treatment for patients with newly diagnosed GBM is surgical resection followed by radiotherapy plus concomitant and adjuvant temozolomide. This treatment protocol may prolong the survival period of the patient, however it is not curative and more effective therapeutic strategies are required. GBM is a type of highly vascularized tumor with increased expression levels of vascular endothelial growth factor (VEGF), which is a significant mediator of angiogenesis. Since angiogenesis is essential for tumor growth, anti‑angiogenic therapies hold potential for the treatment of GBM, and targeting VEGF has demonstrated promising results in previous studies. Bevacizumab (BEV) is a recombinant humanized monoclonal antibody that inhibits VEGF and is approved by the US Food and Drug Administration as a monotherapy treatment for patients with recurrent GBM and is associated with manageable toxicity. Previous studies have demonstrated that BEV may be an effective treatment for recurrent GBM, with prolonged progression‑free survival and overall survival, and maintained patient quality of life and functional status. The present review article briefly outlines the mechanism of action of BEV and summarizes the current literature and clinical trial research on the role of BEV for the treatment of patients with recurrent and newly diagnosed GBM.

View Figures

View References

1	Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW and Kleihues P: The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol. 114:97–109. 2007. View Article : Google Scholar : PubMed/NCBI
2	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
3	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
4	Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10:459–466. 2009. View Article : Google Scholar : PubMed/NCBI
5	Wen PY and DeAngelis LM: Chemotherapy for low-grade gliomas: Emerging consensus on its benefits. Neurology. 68:1762–1763. 2007. View Article : Google Scholar : PubMed/NCBI
6	Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA and Yung WK: Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol. 17:2572–2578. 1999.PubMed/NCBI
7	Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 82:4–6. 1990. View Article : Google Scholar : PubMed/NCBI
8	Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar : PubMed/NCBI
9	Folkman J: Tumor angiogenesis: T herapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI
10	Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–364. 1996. View Article : Google Scholar : PubMed/NCBI
11	Siemann DW and Shi W: Targeting the tumor blood vessel network to enhance the efficacy of radiation therapy. Semin Radiat Oncol. 13:53–61. 2003. View Article : Google Scholar : PubMed/NCBI
12	Miletic H, Niclou SP, Johansson M and Bjerkvig R: Anti-VEGF therapies for malignant glioma, Treatment effects and escape mechanisms. Expert Opin Ther Targets. 13:455–468. 2009. View Article : Google Scholar : PubMed/NCBI
13	Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI
14	Beal K, Abrey LE and Gutin PH: Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma, Analysis of single-agent and combined modality approaches. Radiat Oncol. 6:22011. View Article : Google Scholar : PubMed/NCBI
15	Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, et al: A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 370:699–708. 2014. View Article : Google Scholar : PubMed/NCBI
16	Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, et al: Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 370:709–722. 2014. View Article : Google Scholar : PubMed/NCBI
17	Gil-Gil MJ, Mesia C, Rey M and Bruna J: Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol. 7:123–135. 2013. View Article : Google Scholar : PubMed/NCBI
18	Lu JF, Bruno R, Eppler S, Novotny W, Lum B and Gaudreault J: Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 62:779–786. 2008. View Article : Google Scholar : PubMed/NCBI
19	Specenier P: Bevacizumab in glioblastoma multiforme. Expert Rev Anticancer Ther. 12:9–18. 2012. View Article : Google Scholar : PubMed/NCBI
20	Wong ET, Gautam S, Malchow C, Lun M, Pan E and Brem S: Bevacizumab for recurrent glioblastoma multiforme, A meta-analysis. J Natl Compr Canc Netw. 9:403–407. 2011.PubMed/NCBI
21	Stark-Vance V: Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma. Neuro Oncol. 7:3692005.
22	Vredenburgh JJ, Desjardins A, Herndon JE II, Dowell JM, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Wagner M, et al: Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 13:1253–1259. 2007. View Article : Google Scholar : PubMed/NCBI
23	Vredenburgh JJ, Desjardins A, Herndon JE II, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, et al: Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 25:4722–4729. 2007. View Article : Google Scholar : PubMed/NCBI
24	Desjardins A, VJ, Reardon DA, Herndon JE, Marcello J, Peters K, Gururangan S, Sathornsumetee S, Rich JN and Friedman HS: Long-term survival from the initial trial of bevacizumab and irinotecan. J Clin Oncol. 28(15 Suppl): 1912010.PubMed/NCBI
25	Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, et al: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 27:4733–4740. 2009. View Article : Google Scholar : PubMed/NCBI
26	Cloughesy T, VJ, Day B, Das A and Friedman HS: The BRAIN Investigators: Updated safety and survival of patients with relapsed glioblastoma treated with bevacizumab in the BRAIN study. J Clin Oncol. 28(15 Suppl): 181s2010.
27	Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, et al: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 27:740–745. 2009. View Article : Google Scholar : PubMed/NCBI
28	Cohen MH, Shen YL, Keegan P and Pazdur R: FDA drug approval summary, Bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 14:1131–1138. 2009. View Article : Google Scholar : PubMed/NCBI
29	Chamberlain MC and Johnston SK: Salvage therapy with single agent bevacizumab for recurrent glioblastoma. J Neurooncol. 96:259–269. 2010. View Article : Google Scholar : PubMed/NCBI
30	Raizer JJ, Grimm S, Chamberlain MC, Nicholas MK, Chandler JP, Muro K, Dubner S, Rademaker AW, Renfrow J and Bredel M: A phase 2 trial of single-agent bevacizumab given in an every-3-week schedule for patients with recurrent high-grade gliomas. Cancer. 116:5297–5305. 2010. View Article : Google Scholar : PubMed/NCBI
31	Kreisl TN, Zhang W, Odia Y, Shih JH, Butman JA, Hammoud D, Iwamoto FM, Sul J and Fine HA: A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma. Neuro Oncol. 13:1143–1150. 2011. View Article : Google Scholar : PubMed/NCBI
32	Nagane M, Nishikawa R, Narita Y, Kobayashi H, Takano S, Shinoura N, Aoki T, Sugiyama K, Kuratsu J, Muragaki Y, et al: Phase II study of single-agent bevacizumab in Japanese patients with recurrent malignant glioma. Jpn J Clin Oncol. 42:887–895. 2012. View Article : Google Scholar : PubMed/NCBI
33	Hofer S, Elandt K, Greil R, Hottinger AF, Huber U, Lemke D, Marosi C, Ochsenbein A, Pichler J, Roelcke U, et al: Clinical outcome with bevacizumab in patients with recurrent high-grade glioma treated outside clinical trials. Acta Oncol. 50:630–635. 2011. View Article : Google Scholar : PubMed/NCBI
34	Zhang G, Huang S and Wang Z: A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. J Clin Neurosci. 19:1636–1640. 2012. View Article : Google Scholar : PubMed/NCBI
35	Balañá C, Etxaniz O, Bugés C and Martínez A: Approval denied by the european medicines agency (EMA) for bevacizumab in the treatment of high-grade glioma recurrence A good idea or a grave error? Clin Transl Oncol. 13:209–210. 2011. View Article : Google Scholar : PubMed/NCBI
36	Lai A, Tran A, Nghiemphu PL, Pope WB, Solis OE, Selch M, Filka E, Yong WH, Mischel PS, Liau LM, et al: Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol. 29:142–148. 2011. View Article : Google Scholar : PubMed/NCBI
37	Narayana A, Gruber D, Kunnakkat S, Golfinos JG, Parker E, Raza S, Zagzag D, Eagan P and Gruber ML: A clinical trial of bevacizumab, temozolomide and radiation for newly diagnosed glioblastoma. J Neurosurg. 116:341–345. 2012. View Article : Google Scholar : PubMed/NCBI
38	Vredenburgh JJ, Desjardins A, Reardon DA, Peters KB, Herndon JE II, Marcello J, Kirkpatrick JP, Sampson JH, Bailey L, Threatt S, et al: The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide and irinotecan for newly diagnosed glioblastoma. Clin Cancer Res. 17:4119–4124. 2011. View Article : Google Scholar : PubMed/NCBI
39	Vredenburgh JJ, Desjardins A, Kirkpatrick JP, Reardon DA, Peters KB, Herndon JE II, Marcello J, Bailey L, Threatt S, Sampson J, et al: Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 82:58–66. 2012. View Article : Google Scholar : PubMed/NCBI
40	Armstrong TS, Wen PY, Gilbert MR and Schiff D: Management of treatment-associated toxicites of anti-angiogenic therapy in patients with brain tumors. Neuro Oncol. 14:1203–1214. 2012. View Article : Google Scholar : PubMed/NCBI
41	Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, et al: Bevacizumab for recurrent malignant gliomas: Efficacy, toxicity and patterns of recurrence. Neurology. 70:779–787. 2008. View Article : Google Scholar : PubMed/NCBI
42	Gilbert MR, Wang M, Aldape K, Lassman A, Sorenson AG, Mikkelson T, Groves M, Wener-Wasik M, Regine W and Mehta M: RTOG 0625: A phase II study of bevacizumab with irinotecan in recurrent glioblastoma (GBM). J Clin Oncol. 27(Suppl 15): 89s2009.
43	Gil MJ, de Las Peñas R, Reynés G, Balañá C, Peréz-Segura P, García-Velasco A, Mesia C, Gallego O, Fernández-Chacón C, Martínez-García M, et al: Bevacizumab plus irinotecan in recurrent malignant glioma shows high overall survival in a multicenter retrospective pooled series of the Spanish neuro-oncology research group (GEINO). Anticancer Drugs. 23:659–665. 2012. View Article : Google Scholar : PubMed/NCBI
44	Zuniga RM, Torcuator R, Jain R, Anderson J, Doyle T, Ellika S, Schultz L and Mikkelsen T: Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol. 91:329–336. 2009. View Article : Google Scholar : PubMed/NCBI
45	Quant EC, Norden AD, Drappatz J, Muzikansky A, Doherty L, Lafrankie D, Ciampa A, Kesari S and Wen PY: Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. Neuro Oncol. 11:550–555. 2009. View Article : Google Scholar : PubMed/NCBI
46	Gurevich F and Perazella MA: Renal effects of anti-angiogenesis therapy: Update for the internist. Am J Med. 122:322–328. 2009. View Article : Google Scholar : PubMed/NCBI
47	Zhu X, Wu S, Dahut WL and Parikh CR: Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor, Systematic review and meta-analysis. Am J Kidney Dis. 49:186–193. 2007. View Article : Google Scholar : PubMed/NCBI
48	Wu S, Kim C, Baer L and Zhu X: Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol. 21:1381–1389. 2010. View Article : Google Scholar : PubMed/NCBI
49	Rahmathulla G, Hovey EJ, Hashemi-Sadraei N and Ahluwalia MS: Bevacizumab in high-grade gliomas, A review of its uses, toxicity assessment, and future treatment challenges. Onco Targets Ther. 6:371–389. 2013. View Article : Google Scholar : PubMed/NCBI
50	Poulsen HS, Grunnet K, Sorensen M, Olsen P, Hasselbalch B, Nelausen K, Kosteljanetz M and Lassen U: Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumors. Acta Oncol. 48:52–58. 2009. View Article : Google Scholar : PubMed/NCBI
51	Raval SHS and Dorsett L: Bevacizumab and irinotecan in patients (pts) with recurrent glioblastoma multiforme (GBM). J Clin Oncol. 25(Suppl 18): 20782007.PubMed/NCBI
52	Bokstein F, Shpigel S and Blumenthal DT: Treatment with bevacizumab and irinotecan for recurrent high-grade glial tumors. Cancer. 112:2267–2273. 2008. View Article : Google Scholar : PubMed/NCBI
53	Taillibert S, Hoang-Xuan K, Barrie M, Guiu S, Chauffert B, Cartalat-Carel S, Taillandier L, Fabbro M, Laigre M, Guillamo JS, et al: ANOCEF group: Bevacizumab (B) with irinotecan (I) in recurrent glioblastoma (GBM): A national retrospective cohort of the ANOCEF (Association Des Neuro-Oncologues D'Expression Française) group. Neuro Oncol. 12((Suppl 4)): iv52–iv53. 2010.
54	Keyrouz VF, Elias E, Chahine GY, Comair YG, Dimassi H and Kamar FG: Updated results of a phase II trial of bevacizumab and irinotecan in relapsed high-grade glioma. Neuro Oncol. 12(Suppl 3): iii472010.
55	Pope WB, Lai A, Nghiemphu P, Mischel P and Cloughesy TF: MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology. 66:1258–1260. 2006. View Article : Google Scholar : PubMed/NCBI
56	Nghiemphu PL, Liu W, Lee Y, Than T, Graham C, Lai A, Green RM, Pope WB, Liau LM, Mischel PS, et al: Bevacizumab and chemotherapy for recurrent glioblastoma: A single-institution experience. Neurology. 72:1217–1222. 2009. View Article : Google Scholar : PubMed/NCBI
57	Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE II, Bailey L, Peters KB, Friedman HS and Vredenburgh JJ: Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 118:1302–1312. 2012. View Article : Google Scholar : PubMed/NCBI
58	Verhoeff JJ, Lavini C, van Linde ME, Stalpers LJ, Majoie CB, Reijneveld JC, van Furth WR and Richel DJ: Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma. Ann Oncol. 21:1723–1727. 2010. View Article : Google Scholar : PubMed/NCBI
59	Soffietti R, Trevisan E, Ruda R, Bertero L, Bosa C, Fabrini MG and Lolli I: Phase II trial of bevacizumab with fotemustine in recurrent glioblastoma, Final results of a multicenter study of AINO (Italian Association of Neuro-oncology). J Clin Oncol. 29:2011.PubMed/NCBI
60	Trevisan E, Ruda R, Picco E, Crasto Greco S, Caroli M, Fabrini A, Scotti V, Lolli I, Guarneri D and Soffietti R: Bevacizumab and fotemustine as salvage therapy in recurrent glioblastoma, A phase II multicenter Italian study. Neuro Oncol. 12((Suppl 3)): iii49–iii50. 2010.
61	Hasselbalch B, Lassen U, Hansen S, Holmberg M, Sørensen M, Kosteljanetz M, Broholm H, Stockhausen MT and Poulsen HS: Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide, A phase II trial. Neuro Oncol. 12:508–516. 2010.PubMed/NCBI
62	Shapiro LQ, Beal K, Goenka A, Karimi S, Iwamoto FM, Yamada Y, Zhang Z, Lassman AB, Abrey LE and Gutin PH: Patterns of failure after concurrent bevacizumab and hypofractionated stereotactic radiation therapy for recurrent high-grade glioma. Int J Radiat Oncol Biol Phys. 85:636–642. 2013. View Article : Google Scholar : PubMed/NCBI
63	Sathornsumetee S, Desjardins A, Vredenburgh JJ, McLendon RE, Marcello J, Herndon JE, Mathe A, Hamilton M, Rich JN, Norfleet JA, et al: Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol. 12:1300–1310. 2010.PubMed/NCBI
64	Niyazi M, Ganswindt U, Schwarz SB, Kreth FW, Tonn JC and Geisler J: laF ougère C, Ertl L, Linn J, Siefert A and Belka C: Irradiation and bevacizumab in high-grade glioma retreatment settings. Int J Radiat Oncol Biol Phys. 82:67–76. 2012. View Article : Google Scholar : PubMed/NCBI
65	Hundsberger T, Brügge D, Putora PM, Weder P, Weber J and Plasswilm L: Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas. J Neurooncology. 112:133–139. 2013. View Article : Google Scholar
66	Gutin PH, Iwamoto FM, Beal K, Mohile NA, Karimi S, Hou BL, Lymberis S, Yamada Y, Chang J and Abrey LE: Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 75:156–163. 2009. View Article : Google Scholar : PubMed/NCBI
67	Hainsworth JD, Shih KC, Shepard GC, Tillinghast GW, Brinker BT and Spigel DR: Phase II study of concurrent radiation therapy, temozolomide and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol. 10:240–246. 2012.PubMed/NCBI
68	Herrlinger U, Schafer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Stockhammer F, Ringel F, Braun C, et al: Bevacizumab, irinotecan and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT non-methylated glioblastoma patients: Updated results from the randomized multicenter GLARIUS trial. European J Cancer. 49:S7742013.