Two double blind, placebo-controlled, and randomized phase III studies were conducted, and the results including OS’s were reported at the ASCO Meeting in June 2013, which was the beginning of confusion surrounding this topic. This is a review article not only summarizing the previous evidence, but also looking beyond.
References
[1]
Folkman, J. What is the evidence that tumors are angiogenesis dependent? J. Natl. Cancer Inst. 1990, 82, 4–6, doi:10.1093/jnci/82.1.4.
[2]
Bergers, G.; Benjamin, L.E. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer 2003, 3, 401–410, doi:10.1038/nrc1093.
[3]
Gilbertson, R.J.; Rich, J.N. Making a tumour’s bed: Glioblastoma stem cells and the vascular niche. Nat. Rev. Cancer 2007, 7, 733–736, doi:10.1038/nrc2246.
[4]
Stark-Vance, V. Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma. Neuro-oncology 2005, 7, 369.
[5]
Vredenburgh, J.J.; Desjardins, A.; Herndon, J.E., 2nd; Marcello, J.; Reardon, D.A.; Quinn, J.A.; Rich, J.N.; Sathornsumetee, S.; Gururangan, S.; Sampson, J.; et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J. Clin. Oncol. 2007, 25, 4722–4729, doi:10.1200/JCO.2007.12.2440.
[6]
Yung, W.K.; Albright, R.E.; Olson, J.; Fredericks, R.; Fink, K.; Prados, M.D.; Brada, M.; Spence, A.; Hohl, R.J.; Shapiro, W.; et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br. J. Cancer 2000, 83, 588–593, doi:10.1054/bjoc.2000.1316.
[7]
Friedman, H.S.; Prados, M.D.; Wen, P.Y.; Mikkelsen, T.; Schiff, D.; Abrey, L.E.; Yung, W.K.; Paleologos, N.; Nicholas, M.K.; Jensen, R.; et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol. 2009, 27, 4733–4740, doi:10.1200/JCO.2008.19.8721.
[8]
Gilbert, M.R.; Wang, M.; Aldape, K.; Sorensen, A.G.; Midelsen, T.; Bokstein, F.; Woo, S.Y.; Chmura, S.J.; Choucair, A.K.; Mehta, M. RTOG 0625: A Randomized Phase II Trial of Bevacizumab with either Irinotecan (CPT) or Dose-Dense Temozolomide (TMZ) in Recurrent Glioblastoma (GBM) (XI-2). In Proceedings of the 18th International Conference on Brain Tumor Research and Therapy, Travemünde, Germany, 18–20 November 2010.
[9]
Kreisl, T.N.; Kim, L.; Moore, K.; Duic, P.; Royce, C.; Stoud, I.; Garren, N.; Mackey, M.; Butman, J.A.; 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. 2009, 27, 740–745, doi:10.1200/JCO.2008.16.3055.
[10]
Sathornsumetee, S.; Desjardins, A.; Vredenburgh, J.J.; McLendon, R.E.; Marcello, J.; Herndon, J.E.; Mathe, A.; Hamilton, M.; Rich, J.N.; Norfleet, J.A.; et al. Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro-oncology 2010, 12, 1300–1310.
[11]
Reardon, D.A.; Desjardins, A.; Vredenburgh, J.J.; Gururangan, S.; Sampson, J.H.; Sathornsumetee, S.; McLendon, R.E.; Herndon, J.E., 2nd; Marcello, J.E.; Norfleet, J.; et al. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: A phase II study. Br. J. Cancer 2009, 101, 1986–1994, doi:10.1038/sj.bjc.6605412.
[12]
Soffietti, R.; Ruda, R.; Trevisan, E. Pase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: A multicenter Italian study (abstract 2012). J. Clin. Oncol. 2009, 27, 90s, doi:10.1200/JCO.2009.23.7990.
[13]
Batchelor, T.T.; Gilbert, M.R.; Supko, J.G.; Carson, K.A.; Nabors, L.B.; Grossman, S.A.; Lesser, G.J.; Mieelsen, T.; Phuphanich, S.; NABTT CNS Consortium. Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: Final report of NABTT 97–11. Neuro-oncology 2004, 6, 21–27, doi:10.1215/S1152851703000218.
[14]
Cloughesy, T.F.; Filka, E.; Kuhn, J.; Nelsonk, G.; Kabbinavar, F.; Friedman, H.; Miller, L.L.; Elfring, G.L. Two studies evaluating irinotecan treatment for recurrent malignant glioma using an every-3-week regimen. Cancer 2003, 97, 2381–2386, doi:10.1002/cncr.11306.
[15]
Friedman, H.S.; Petros, W.P.; Friedman, A.H.; Schaaf, L.J.; Kerby, T; Lawyer, J.; Parry, M.; Houghton, P.F.; Lovell, S.; Rasheed, K.; et al. Irinotecan therapy in adults with recurrent or progressive malignant glioma. J. Clin. Oncol. 1999, 17, 1516–1525.
[16]
Kreisl, T.N.; Zhang, W.; Odia, Y.; Shih, J.H.; Butman, J.A.; Hammoud, D.; Iwamoto, F.M.; Sul, J.; Fine, H.A. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma. Neuro-oncology 2011, 13, 1143–1150, doi:10.1093/neuonc/nor091.
[17]
Prados, M.D.; Lamborn, K.; Yung, W.K; Jaeckle, K.; Robins, H.I.; Mehta, M.; Fine, H.A.; Wen, P.Y.; Cloughesy, T.; Chang, S.; et al. A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study. Neuro-oncology 2006, 8, 189–193, doi:10.1215/15228517-2005-010.
[18]
Thompson, E.M.; Frenkel, E.P.; Neuwelt, E.A. The paradoxical effect of bevacizumab in the therapy of malignant gliomas. Neurology 2011, 76, 87–93, doi:10.1212/WNL.0b013e318204a3af.
[19]
Verhoeff, J.J.; van Tellingen, O.; Claes, A.; Stalpers, L.J.; van Linde, M.E.; Richel, D.J.; Leenders, W.P.; van Furth, W.R. Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme. BMC Cancer 2009, 9, 444, doi:10.1186/1471-2407-9-444.
[20]
Claes, A.; Wesseling, P.; Jeuken, J.; Maassc, C.; Heerschap, A.; Leenders, W.P. Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization. Mol. Cancer Ther. 2008, 7, 71–78.
[21]
Taal, W.; Oosterkamp, H.M.; Walenkamp, A.M.E.; Beerepoot, L.V.; Hanse, M.; Buter, J.; Honkoop, A.; Boerman, D.; De Vos, F.Y.F.L.; Jansen, R.L.; et al. A randomized phase II study of bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma: The Dutch BELOB study. Chicago, IL, USA, 1 June 2013. Abstract #2001; American Society for Clinical Oncology (ASCO).
[22]
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. 2012, 42, 887–895, doi:10.1093/jjco/hys121.
[23]
Field, K.M.; Simes, J.; Wheeler, H.; Hovery, E.J.; Nowak, A.K.; Cher, L.; Brown, C.; Livingstone, A.; Sawkins, K.; Rosentahl, M.; et al. A randomized phase II study of carboplatin and bevacizumab in recurrent glioblastoma multiforme (CABARET). Chicago, IL, USA, 3 June 2013. Abstract #2017; American Society for Clinical Oncology (ASCO).
[24]
Herrlinger, U.; Schaefer, N; Steinbach, J.P.; Weyerbrock, A.; Hau, P.; Goldbrunner, R.; Friedrich, F.; Stockhammer, F.; Ringel, F.; et al. Bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-non-methylated glioblastoma patients: First results from the randomized multicenter GLARIUS trial. Chicago, USA, 1 June 2013. Abstract #LBA2000; American Society for Clinical Oncology (ASCO).
[25]
Reardon, D.A.; Desjardins, A.; Peters, K.; Gururangan, S.; Sampson, J.; Rich, J.N.; McLendon, R.; Herndon, J.E., II; Marcello, J.; Threatt, S.; et al. Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. J. Neurooncol. 2011, 103, 371–379, doi:10.1007/s11060-010-0403-6.
[26]
Reardon, D.A.; Desjardins, A.; Peters, K.B.; Vredenburgh, J.J.; Gururangan, S.; Sampson, J.H.; McLendon, R.E.; Herndon, J.E., 2nd; Coan, A.; Threatt, S.; et al. Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. Cancer 2011, 117, 5351–5358, doi:10.1002/cncr.26188.
[27]
Quant, E.C.; Norden, A.D.; Drappatz, J.; Muzikansky, A.; Doherty, L.; Lafrankie, D.; Ciampa, A.; Kesari, S.; Wen, P.Y. Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. Neuro-oncology 2009, 11, 550–555, doi:10.1215/15228517-2009-006.
[28]
Zuniga, R.M.; Torcuator, R.; Jain, R.; Anderson, J.; Doyle, T.; Schultz, L.; Mikkelsen, T. Rebound tumour progression after the cessation of bevacizumab therapy in patients with recurrent high-grade glioma. J. Neurooncol. 2010, 99, 237–242, doi:10.1007/s11060-010-0121-0.
[29]
Chamberlain, M.C. Bevacizumab for the treatment of recurrent glioblastoma. Clin. Med. Insights Oncol. 2011, 5, 117–129, doi:10.4137/CMO.S7232.
[30]
Kesselheim, J.C.; Norden, A.D.; Wen, P.Y.; Joffe, S. Discontinuing bevacizumab in patients with glioblastoma: An ethical analysis. Oncologist 2011, 16, 1435–1439, doi:10.1634/theoncologist.2011-0047.
Bennouna, J.; Sastre, J.; Arnold, D.; Oesterlund, P.; Greil, R.; van Cutsem, E.; von Moos, R.; Vieitez, J.M.; Bouche, O.; Borg, C.; et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): A randomised phase 3 trial. Lancet Oncol. 2013, 14, 29–37, doi:10.1016/S1470-2045(12)70477-1.
[33]
Reardon, D.A.; Herndon, J.E., 2nd; Peters, K.B.; Desjardins, A.; Coan, A.; Lou, E.; Sumrall, A.L.; Turner, S.; Lipp, E.S.; Sathornsumetee, S.; et al. Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients. Br. J. Cancer 2012, 107, 1481–1487, doi:10.1038/bjc.2012.415.
[34]
Omuro, A.; Chan, T.A.; Abrey, L.E.; Khasraw, M.; Reiner, A.S.; Kaley, T.J.; Deangelis, L.M.; Lassman, A.B.; Nolan, C.P.; Garvilovic, I.T.; et al. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro-oncology 2013, 15, 242–250, doi:10.1093/neuonc/nos295.
[35]
Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy. In Proceedings of the 17th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO), Washington, DC, USA, 16 November 2012; Piccioni, D.E., Selfridge, J., Mody, R., Quan, J., Zurayk, M., Li, S., Chen, W., Chou, A., Liau, L., Green, R., et al, Eds.; Oxford University Press: Oxford, UK, 2012. Abstract #NO-97.
[36]
Wen, P.Y.; Macdonald, D.R.; Reardon, D.A.; Cloughesy, T.F.; Sorensen, A.G.; Galanis, E.; Degroot, J.; Wick, W.; Gilbert, M.R.; Lassman, A.B.; et al. Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group. J. Clin. Oncol. 2010, 28, 1963–1972, doi:10.1200/JCO.2009.26.3541.
[37]
Holash, J.; Maisonpierre, P.C.; Compton, D.; Boland, P.; Alexander, C.R.; Zagzag, D.; Yancopoulos, G.D.; Wiegand, S.J. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999, 284, 1994–1998, doi:10.1126/science.284.5422.1994.
[38]
Iwamoto, F.M.; Abrey, L.E.; Beal, K.; Gutin, P.H.; ROsenblum, M.K.; Reuter, V.E.; DeAngelis, L.M.; Lassman, A.B. Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology 2009, 73, 1200–1206, doi:10.1212/WNL.0b013e3181bc0184.
[39]
Norden, A.D.; Young, G.S.; Setayesh, K.; Muzikansky, A.; Klufas, R.; Ross, G.L.; Clampa, A.S.; Ebbeling, L.G.; Levy, B.; Drappatz, J.; et al. Bevacizumab for recurrent malignant gliomas: Efficacy, toxicity, and patterns of recurrence. Neurology 2008, 70, 779–787, doi:10.1212/01.wnl.0000304121.57857.38.
[40]
Pope, W.B.; Xia, Q.; Das, A.; Hambleton, J.; Kim, H.; Brwon, M.; Goldin, J.; Coughesy, T.F. Patterns of progression in patients with glioblastoma at first or second relapse treated with bevacizumab alone or in combination with irinotecan in the BRAIN study. Neuro-oncology 2009, 11, 626. (Abstract # 270 from the 2009 Joint Meeting of SNO and AANS/CNS Section on Tumors).
[41]
Chamberlain, M.C. Radiographic patterns of relapse in glioblastoma. J. Neurooncol. 2011, 101, 319–323, doi:10.1007/s11060-010-0251-4.
[42]
Wick, W.; Cloughesy, T.F.; Nishikawa, R.; Mason, W.; Saran, F.; Henriksson, R.; Hilton, M.; Kerloeguen, Y.; Chino, O.L. Tumor response based on adapted Macdonald criteria and assessment of pseudoprogression (PsPD) in the phase III AVAglio trial of bevacizumab (Bv) plus temozolomide (T) plus radiotherapy (RT) in newly diagnosed glioblastoma (GBM). Chicago, IL, USA, 1 June 2013. Abstract #2002; American Society for Clinical Oncology (ASCO).
[43]
Wong, E.T.; Gautam, S.; Malchow, C.; Lun, M.; Pan, E.; Brem, S. Bevacizumab for recurrent glioblastoma multiforme: A meta-analysis. J. Natl. Compr. Canc. Netw. 2011, 9, 403–407.
[44]
Bocci, G.; Loupakis, F. The possible role of chemotherapy in antiangiogenic drug resistance. Med. Hypotheses 2012, 78, 646–648, doi:10.1016/j.mehy.2012.02.001.
[45]
Grothey, A.; Sugrue, M.M.; Purdie, D.M.; Dong, W.; Sargent, D.; Hendrick, E.; Kozloff, M. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: Results from a large observational cohort study (BRiTE). J. Clin. Oncol. 2008, 26, 5326–5334, doi:10.1200/JCO.2008.16.3212.
[46]
Ebos, J.M.; Lee, C.R.; Cruz-Munoz, W.; Bjamason, G.A.; Christensen, J.G.; Kerbel, R.S. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009, 15, 232–239, doi:10.1016/j.ccr.2009.01.021.
[47]
Paez-Ribes, M.; Allen, E.; Hudock, J.; Takeda, T.; Okuyama, H.; Vinals, F.; Inoue, M.; Bergers, G.; Hanahan, D.; Casanovas, O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009, 15, 220–231, doi:10.1016/j.ccr.2009.01.027.
[48]
Gherardi, E.; Birchmeier, W.; Birchmeier, C.; Vande Woude, G. Targeting MET in cancer: Rationale and progress. Nat. Rev. Cancer 2012, 12, 89–103.
[49]
Pennacchietti, S.; Michieli, P.; Galluzzo, M.; Mazzone, M.; Giordano, S.; Comoglio, P.M. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003, 3, 347–361, doi:10.1016/S1535-6108(03)00085-0.
[50]
Thiery, J.P.; Acloque, H.; Huang, R.Y.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139, 871–890, doi:10.1016/j.cell.2009.11.007.
[51]
Yilmaz, M.; Christofori, G. Mechanisms of motility in metastasizing cells. Mol. Cancer Res. 2010, 8, 629–642, doi:10.1158/1541-7786.MCR-10-0139.
[52]
Lu, K.V.; Chang, J.P.; Parachoniak, C.A.; Pandika, M.M.; Aghi, M.K.; Meyronet, D.; Isachenko, N.; Fouse, S.D.; Phillips, J.J.; Cheresh, D.A.; et al. VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell 2012, 22, 21–35, doi:10.1016/j.ccr.2012.05.037.
[53]
Cooke, V.G.; LeBleu, V.S.; Keskin, D.; Khan, Z.; O’Conneill, J.T.; Teng, Y.; Duncan, M.B.; Xie, L.; Maeda, G.; Vong, S.; et al. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 2012, 21, 66–81, doi:10.1016/j.ccr.2011.11.024.
[54]
Narayana, A.; Kelly, P.; Golfinos, J.; Parker, E.; Johnson, G.; Knopp, E.; Zagzag, D.; Fischer, I.; Raza, S.; Medabalmi, P.; et al. Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: Impact on local control and patient survival. J. Neurosurg. 2009, 110, 173–180, doi:10.3171/2008.4.17492.
