Advances in Combination of Antiangiogenic Agents Targeting VEGF-binding and Conventional Chemotherapy and Radiation for Cancer Treatment
Article Outline
Despite great efforts and resources being devoted to treatment, the incidence and mortality of numerous cancers have not decreased in recent decades. This is a result of the resistance of cancer cells to chemotherapeutic agents and radio-therapy. The development of antiangiogenic agents that target vascular endothelial growth factor (VEGF) provides a new option for treatment of cancer. Major advances have been achieved with cancer therapy based on antiangiogenic VEGF-targeted agents in the past few years, and some of the recently approved therapies are now being used in daily clinical practice. A further challenge is finding a more efficacious combination of antiangiogenic VEGF-targeted therapies and conventional radio- and chemotherapies. This review outlines the current preclinical and clinical cancer treatments using optimized combinations of antiangiogenic VEGF-targeted agents and conventional radiochemotherapy and highlights that better scheduling for the combination of radiochemotherapy and antiangiogenic VEGF-targeted agents should be developed to achieve better treatment outcomes.
Key Words: antiangiogenic agents , bevacizumab , VEGF-targeted agents , VEGF-Trap
No full text is available. To read the body of this article, please view the PDF online.
References
- . Structure and function of VEGF/VEGF-receptor system involved in angiogenesis . Cell Struct Funct . 2001;26:25–35
- . Vascular and haematopoietic stem cells: Novel targets for anti-angiogenesis therapy? . Nature Rev Cancer . 2002;2:826–835
- . Fundamental concepts of the angiogenic process . Curr Mol Med . 2003;3:643–651
- . Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis . J Clin Oncol . 2005;23:1011–1027
- . The biology of VEGF and its receptors . Nat Med . 2003;9:669–676
- . Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid . Science . 1983;219:983–985
- . The potential of antiangiogenic therapy in non-small cell lung cancer . Clin Cancer Res . 2007;13:1961–1970
- AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients . Cancer Cell . 2007;11:83–95
- Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer . Nat Med . 2004;10:145–147
- . VEGF as a therapeutic target in cancer . Oncology . 2005;69(Suppl):11–16
- VEGF-Trap: a VEGF blocker with potent antitumor effects . Proc Natl Acad Sci USA . 2002;99:11393–11398
- . Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cyto-toxic therapy in preclinical studies . Cancer Res . 2005;65:671–680
- . Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro . Angiogenesis . 2004;7:335–345
- Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders . Cancer Res . 1997;57:4593–4599
- Anti-VEGF antibody suppresses primary tumor growth and metastasis in an experimental model of Wilms' tumor . J Pediatr Surg . 2000;35:30–32
- . Prevention of thecal angiogenesis, antral follicular growth, and ovulation in the primate by treatment with vascular endothelial growth factor Trap R1R2 . Endocrinology . 2002;143:2797–2807
- . Vascular endothelial growth factor-trap suppresses tumorigenicity of multiple pancreatic cancer cell lines . Clin Cancer Res . 2004;10:3327–3332
- Regression of established tumors and metastases by potent vascular endothelial growth factor blockade . Proc Natl Acad Sci USA . 2003;100:7785–7790
- . Recombinant anti-vascular endothelial growth factor fusion protein efficiently suppresses choroidal neovascularization in monkeys . Mol Vis . 2008;14:37–49
- . The pharmacology study of a new recombinant human VEGF receptor-fc fusion protein on experimental choroidal neovascularization . Pharm Res . 2009;26:204–210
- Rapid vascular regrowth in tumors after reversal of VEGF inhibition . J Clin Invest . 2006;116:2610–2621
- Targeting the VEGF pathway: antiangio-genic strategies in the treatment of non-small cell lung cancer . Crit Rev Oncol Hematol . 2008;68:183–196
- . Lessons from phase III clinical trials on anti-VEGF therapy for cancer . Nat Clin Pract Oncol . 2006;3:24–40
- . Antiangiogenic therapy: a universal chemosensitization strategy for cancer? . Science . 2006;312:1171–1175
- Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation . Cancer Res . 1999;59:3374–3378
- Vascular endothelial growth factor enhances endothelial cell survival and tumor radioresistance . Cancer J . 2002;8:47–54
- Anti-vascular endothelial growth factor treatment augments tumor radiation response under nor-moxic or hypoxic conditions . Cancer Res . 2000;60:5565–5570
- . Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization . Clin Cancer Res . 2007;13:3395–3402
- Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability . Int J Radiat Oncol Biol Phys . 2008;71:1372–1380
- Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: phase I trial results . Int J Radiat Oncol Biol Phys . 2007;68:472–478
- . Usefulness of HIF-1 imaging for determining optimal timing of combining bevacizumab and radiotherapy . Int J Radiat Oncol Biol Phys . 2009;75:463–467
- VEGF trap in combination with radiotherapy improves tumor control in U87 glioblas-toma . Int J Radiat Oncol Biol Phys . 2007;67:1526–1537
- . Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin . Anticancer Res . 1999;19:4203–4214
- Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor . J Pediatr Surg . 2001;36:1177–1181
- . Antibody to vascular endothelial growth factor slows growth of an androgen-independent xenograft model of prostate cancer . Clin Cancer Res . 2002;8:3226–3231
- . Vascular endothelial growth factor immunoneutralization plus Paclitaxel markedly reduces tumor burden and ascites in athymic mouse model of ovarian cancer . Am J Pathol . 2002;161:1917–1924
- Effect of antivascular endothe-lial growth factor treatment on the intratumoral uptake of CPT-11 . Br J Cancer . 2003;88:1979–1986
- . Carboplatin selectively induces the VEGF stress response in endothelial cells: potentiation of antitumor activity by combination treatment with antibody to VEGF . Int J Cancer . 2004;110:343–351
- Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xeno-grafts results in improved delivery and efficacy of systemically administered chemotherapy . Clin Cancer Res . 2007;13:3942–3950
- . Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study . Breast Cancer Res Treat . 2003;79:391–397
- Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients . Clin Cancer Res . 2006;12:3124–3129
- Phase II study of docetaxel (D) plus bevacizumab (B) in Her/2 negative metastatic breast carcinoma (MBC) . J Clin Oncol . 2006;24:605s; (abstract 13047). 2006 ASCO Annual Meeting Proceedings Part I.
- Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer . J Clin Oncol . 2005;23:792–799
- A randomized phase III trial of pacli-taxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100) . Breast Cancer Res . 2005;94(Suppl):S6; (abstract 3).
- Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer . J Clin Oncol . 2003;21:60–65
- Addition of bevacizumab to bolus flu-orouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial . J Clin Oncol . 2005;23:3697–3705
- Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer . N Engl J Med . 2006;355:2542–2550
- Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer . J Clin Oncol . 2004;22:2184–2191
- Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer . J Clin Oncol . 2005;23:8033–8040
- Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer . N Engl J Med . 2004;350:2335–2342
- . First efficacy and safety results from XELOX-1/NO16966, a randomised 2 × 2 factorial phase III trial of XELOX vs FOLFOX4 plus bevacizumab or placebo in first-line metastatic colorectal cancer (MCRC) . Ann Oncol . 2006;17(Suppl):LBA3; [Abstract]
- Bevacizumab in combination with XELOX or FOLFOX4: efficacy results from XELOX-1/NO16966, a randomized phase III trial in the first-line treatment of metastatic colorectal cancer (MCRC) . Gastrointestinal Cancers Symposium . 2007; abstract 238.
- . Safety and efficacy of oxaliplatin/flu-oropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): final analysis of the TREE-Study . Proc Am Soc Clin Oncol . 2006; abstract 3510.
- . Vascular endothelial growth factor trap combined with paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model . Clin Cancer Res . 2005;11:6966–6971
- . SU5416 delays wound healing through inhibition of TGF-beta 1 activation . Cancer Biol Ther . 2002;1:121–126
- Irinotecan plus fluorouracil/leucovorin for metastatic colorectal cancer: a new survival standard . Oncologist . 2001;6:81–91
- . Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload . Hypertension . 2006;47:887–893
- . Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy . Nat Med . 2001;7:987–989
PII: S1726-4901(10)70062-9
doi:10.1016/S1726-4901(10)70062-9
© 2010 Elsevier. Published by Elsevier Inc. All rights reserved.
