Skip to main content
Top
Published in: Tumor Biology 3/2016

01-03-2016 | Review

Cediranib in ovarian cancer: state of the art and future perspectives

Authors: Ilary Ruscito, Maria Luisa Gasparri, Claudia Marchetti, Caterina De Medici, Carlotta Bracchi, Innocenza Palaia, Sara Imboden, Michael D. Mueller, Andrea Papadia, Ludovico Muzii, Pierluigi Benedetti Panici

Published in: Tumor Biology | Issue 3/2016

Login to get access

Abstract

Despite the dramatic improvements achieved in cancer treatment through a better understanding of the tumor biology, ovarian cancer is still characterized by a poor prognosis: most patients diagnosed with this disease will ultimately die from it. In various clinical trials conducted over a time span of two decades, new combinations of conventional chemotherapy regimens have failed to achieve significant improvements in oncologic outcome in ovarian cancer patients. We have now entered an era of “personalized medicine” in which new medications are designed to specifically target molecular pathways involved in carcinogenesis and cancer progression. Encouraging results in different tumor types have been reported, applying an increasing number of target therapies that are still under evaluation. In this setting, one of the most successfully targeted molecular pathways is tumor angiogenesis. Bevacizumab, a monoclonal antibody binding vascular endothelial growth factor (VEGF), has been recently incorporated in the treatment of primary and recurrent ovarian cancer patients after multiple phase III randomized controlled trials have proven its clinical benefit. Based on these positive results, more anti-angiogenic molecules using different mechanisms of action have been developed and are currently under investigation. Among these molecules, the tyrosine kinases inhibitors are probably the most promising ones. Cediranib is a tyrosine kinase inhibitor targeting VEGF receptors that has been tested in various trials with promising results. The aim of this manuscript is to review the current role of cediranib in the treatment of ovarian cancer and to present an overview of the ongoing clinical trials in this setting.
Literature
2.
go back to reference Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95(1):S161–92.CrossRefPubMed Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95(1):S161–92.CrossRefPubMed
4.
go back to reference Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.CrossRefPubMed Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.CrossRefPubMed
5.
go back to reference Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.CrossRefPubMed Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.CrossRefPubMed
6.
go back to reference Matulonis UA, Berlin S, Ivy P, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol. 2009;27:5601–6.CrossRefPubMedPubMedCentral Matulonis UA, Berlin S, Ivy P, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol. 2009;27:5601–6.CrossRefPubMedPubMedCentral
7.
go back to reference Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005;16:1688–94.CrossRefPubMed Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005;16:1688–94.CrossRefPubMed
8.
go back to reference Friedlander M, Hancock KC, Rischin D, et al. A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010;119:32–7.CrossRefPubMed Friedlander M, Hancock KC, Rischin D, et al. A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010;119:32–7.CrossRefPubMed
9.
go back to reference Ide ABGN, Warren SL. Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol. 1939;42:891–9. Ide ABGN, Warren SL. Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol. 1939;42:891–9.
10.
go back to reference Plouet J, Moukadiri H. Specific binding of vasculotropin to bovine brain capillary endothelial cells. Biochimie. 1990;72:51–5.CrossRefPubMed Plouet J, Moukadiri H. Specific binding of vasculotropin to bovine brain capillary endothelial cells. Biochimie. 1990;72:51–5.CrossRefPubMed
11.
go back to reference Leone Roberti Maggiore U, Bellati F, Ruscito I, et al. Monoclonal antibodies therapies for ovarian cancer. Expert Opin Biol Ther. 2013;13:739–64.CrossRefPubMed Leone Roberti Maggiore U, Bellati F, Ruscito I, et al. Monoclonal antibodies therapies for ovarian cancer. Expert Opin Biol Ther. 2013;13:739–64.CrossRefPubMed
12.
go back to reference Bellati F, Napoletano C, Gasparri ML, et al. Monoclonal antibodies in gynecological cancer: a critical point of view. Clin Dev Immunol. 2011;2011:890758.CrossRefPubMedPubMedCentral Bellati F, Napoletano C, Gasparri ML, et al. Monoclonal antibodies in gynecological cancer: a critical point of view. Clin Dev Immunol. 2011;2011:890758.CrossRefPubMedPubMedCentral
13.
go back to reference Bellati F, Napoletano C, Gasparri ML, et al. Current knowledge and open issues regarding bevacizumab in gynaecological neoplasms. Crit Rev Oncol Hematol. 2012;83:35–46.CrossRefPubMed Bellati F, Napoletano C, Gasparri ML, et al. Current knowledge and open issues regarding bevacizumab in gynaecological neoplasms. Crit Rev Oncol Hematol. 2012;83:35–46.CrossRefPubMed
14.
go back to reference Marchetti C, Gasparri ML, Ruscito I, et al. Advances in anti-angiogenic agents for ovarian cancer treatment: the role of trebananib (AMG 386). Crit Rev Oncol Hematol. 2015;94:302–10.CrossRefPubMed Marchetti C, Gasparri ML, Ruscito I, et al. Advances in anti-angiogenic agents for ovarian cancer treatment: the role of trebananib (AMG 386). Crit Rev Oncol Hematol. 2015;94:302–10.CrossRefPubMed
15.
go back to reference Wedge SR, Kendrew J, Hennequin LF, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005;65:4389–400.CrossRefPubMed Wedge SR, Kendrew J, Hennequin LF, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005;65:4389–400.CrossRefPubMed
16.
go back to reference Heckman CA, Holopainen T, Wirzenius M, et al. The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis. Cancer Res. 2008;68:4754–62.CrossRefPubMed Heckman CA, Holopainen T, Wirzenius M, et al. The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis. Cancer Res. 2008;68:4754–62.CrossRefPubMed
17.
go back to reference Gomez-Rivera F, Santillan-Gomez AA, Younes MN, et al. The tyrosine kinase inhibitor, AZD2171, inhibits vascular endothelial growth factor receptor signaling and growth of anaplastic thyroid cancer in an orthotopic nude mouse model. Clin Cancer Res. 2007;13:4519–27.CrossRefPubMed Gomez-Rivera F, Santillan-Gomez AA, Younes MN, et al. The tyrosine kinase inhibitor, AZD2171, inhibits vascular endothelial growth factor receptor signaling and growth of anaplastic thyroid cancer in an orthotopic nude mouse model. Clin Cancer Res. 2007;13:4519–27.CrossRefPubMed
18.
go back to reference Decio A, Cesca M, Bizzaro F, et al. Cediranib combined with chemotherapy reduces tumor dissemination and prolongs the survival of mice bearing patient-derived ovarian cancer xenografts with different responsiveness to cisplatin. Clin Exp Metastasis. 2015;32:647–58.CrossRefPubMed Decio A, Cesca M, Bizzaro F, et al. Cediranib combined with chemotherapy reduces tumor dissemination and prolongs the survival of mice bearing patient-derived ovarian cancer xenografts with different responsiveness to cisplatin. Clin Exp Metastasis. 2015;32:647–58.CrossRefPubMed
19.
go back to reference Drevs J, Siegert P, Medinger M, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2007;25:3045–54.CrossRefPubMed Drevs J, Siegert P, Medinger M, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2007;25:3045–54.CrossRefPubMed
20.
go back to reference Trarbach T, Schultheis B, Gauler TC, et al. Phase I open-label study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours. Investig New Drugs. 2012;30:1962–71.CrossRef Trarbach T, Schultheis B, Gauler TC, et al. Phase I open-label study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours. Investig New Drugs. 2012;30:1962–71.CrossRef
21.
go back to reference Musella A, Marchetti C, Gasparri ML, et al. PARP inhibition: a promising therapeutic target in ovarian cancer. Cell Mol Biol (Noisy-le-Grand). 2015;61:44–61. Musella A, Marchetti C, Gasparri ML, et al. PARP inhibition: a promising therapeutic target in ovarian cancer. Cell Mol Biol (Noisy-le-Grand). 2015;61:44–61.
22.
go back to reference Marchetti C, Imperiale L, Gasparri ML, et al. Olaparib, PARP1 inhibitor in ovarian cancer. Expert Opin Investig Drugs. 2012;21:1575–84.CrossRefPubMed Marchetti C, Imperiale L, Gasparri ML, et al. Olaparib, PARP1 inhibitor in ovarian cancer. Expert Opin Investig Drugs. 2012;21:1575–84.CrossRefPubMed
23.
go back to reference Liu JF, Tolaney SM, Birrer M, et al. A phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49:2972–8.CrossRefPubMedPubMedCentral Liu JF, Tolaney SM, Birrer M, et al. A phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49:2972–8.CrossRefPubMedPubMedCentral
24.
go back to reference Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15:1207–14.CrossRefPubMedPubMedCentral Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15:1207–14.CrossRefPubMedPubMedCentral
25.
go back to reference Robinson ES, Matulonis UA, Ivy P, et al. Rapid development of hypertension and proteinuria with cediranib, an oral vascular endothelial growth factor receptor inhibitor. Clin J Am Soc Nephrol. 2010;5:477–83.CrossRefPubMedPubMedCentral Robinson ES, Matulonis UA, Ivy P, et al. Rapid development of hypertension and proteinuria with cediranib, an oral vascular endothelial growth factor receptor inhibitor. Clin J Am Soc Nephrol. 2010;5:477–83.CrossRefPubMedPubMedCentral
26.
go back to reference Mulder SF, Boers-Sonderen MJ, van der Heijden HF, et al. A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion. Target Oncol. 2014;9:331–8.CrossRefPubMed Mulder SF, Boers-Sonderen MJ, van der Heijden HF, et al. A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion. Target Oncol. 2014;9:331–8.CrossRefPubMed
27.
go back to reference Hirte H, Lheureux S, Fleming GF, et al. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia. Gynecol Oncol. 2015;138:55–61.CrossRefPubMed Hirte H, Lheureux S, Fleming GF, et al. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia. Gynecol Oncol. 2015;138:55–61.CrossRefPubMed
28.
go back to reference Raja FA, Griffin CL, Qian W, et al. Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. Br J Cancer. 2011;105:884–9.CrossRefPubMedPubMedCentral Raja FA, Griffin CL, Qian W, et al. Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. Br J Cancer. 2011;105:884–9.CrossRefPubMedPubMedCentral
29.
go back to reference Ledermann JA, Perren TJ, Raja FA, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial. Eur J Cancer, 2013; 49:abstrLBA10. Ledermann JA, Perren TJ, Raja FA, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial. Eur J Cancer, 2013; 49:abstrLBA10.
30.
31.
go back to reference Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62.CrossRefPubMed Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62.CrossRefPubMed
Metadata
Title
Cediranib in ovarian cancer: state of the art and future perspectives
Authors
Ilary Ruscito
Maria Luisa Gasparri
Claudia Marchetti
Caterina De Medici
Carlotta Bracchi
Innocenza Palaia
Sara Imboden
Michael D. Mueller
Andrea Papadia
Ludovico Muzii
Pierluigi Benedetti Panici
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4781-4

Other articles of this Issue 3/2016

Tumor Biology 3/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine