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Published in: Targeted Oncology 4/2010

01-12-2010 | Original Research

Investigation of the efficacy of a bevacizumab-cetuximab-cisplatin regimen in treating head and neck squamous cell carcinoma in mice

Authors: Yixiang Wang, Ling Dong, Qingwei Bi, Xiao Li, Dengcheng Wu, Xiyuan Ge, Xiaoxia Zhang, Jia Fu, Chengfei Zhang, Cunyu Wang, Shenglin Li

Published in: Targeted Oncology | Issue 4/2010

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Abstract

The efficacy of bevacizumab plus cetuximab-based chemotherapy remains unclear in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the anticancer efficacy of a bevacizumab-cetuximab-cisplatin triple-agent combination in treating mouse HNSCC. SCC-VII tumor-bearing C3H mice were treated with bevacizumab, cetuximab and cisplatin either alone or in various combinations. In vivo results showed that the largest delay in tumor growth and the maximum increase in survival were not in the triple-agent combination therapy, but in the bevacizumab plus cisplatin therapy. TUNEL assay showed that the apoptosis indices in bevacizumab plus cisplatin group and a triple-agent combination group were 31.6 ± 12.0% and 6.9 ± 1.3%, respectively. Western blot showed that down-regulation of Bcl-2 and up-regulation of cleaved caspase-3 contributed to the anticancer effect of a triple-agent combination and bevacizumab plus cisplatin. Moreover, the maximum level of cleaved caspase-3 expression was not found in the triple-agent combination group but in the bevacizumab plus cisplatin group. Bevacizumab plus cisplatin therapy is better than bevacizumab-cetuximab-cisplatin triple therapy in the mouse HNSCC model. Our findings suggest that the bevacizumab-cetuximab-cisplatin regimen may not be suitable for treating HNSCC.
Literature
1.
go back to reference Tabernero J (2007) The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 5(3):203–220CrossRefPubMed Tabernero J (2007) The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 5(3):203–220CrossRefPubMed
2.
go back to reference Imai K, Takaoka A (2006) Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 6(9):714–727CrossRefPubMed Imai K, Takaoka A (2006) Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 6(9):714–727CrossRefPubMed
3.
go back to reference Marshall J (2006) Clinical implications of the mechanism of epidermal growth factor receptor inhibitors. Cancer 107(6):1207–1218CrossRefPubMed Marshall J (2006) Clinical implications of the mechanism of epidermal growth factor receptor inhibitors. Cancer 107(6):1207–1218CrossRefPubMed
4.
go back to reference No authors listed (2004) Two new drugs for colon cancer. Med Lett Drugs Ther 46(1184):46–48 No authors listed (2004) Two new drugs for colon cancer. Med Lett Drugs Ther 46(1184):46–48
5.
go back to reference Aita M, Fasola G, Defferrari C, Brianti A, Bello MG, Follador A, Sinaccio G, Pronzato P, Grossi F (2008) Targeting the VEGF pathway: Antiangiogenic strategies in the treatment of non-small cell lung cancer. Crit Rev Oncol Hematol 68(3):183–196CrossRefPubMed Aita M, Fasola G, Defferrari C, Brianti A, Bello MG, Follador A, Sinaccio G, Pronzato P, Grossi F (2008) Targeting the VEGF pathway: Antiangiogenic strategies in the treatment of non-small cell lung cancer. Crit Rev Oncol Hematol 68(3):183–196CrossRefPubMed
6.
go back to reference American Cancer Society (2008) Cancer facts & figures 2008. Atlanta: American Cancer Society 2008:15–16 American Cancer Society (2008) Cancer facts & figures 2008. Atlanta: American Cancer Society 2008:15–16
7.
go back to reference Tejani MA, Cohen RB, Mehra R (2010) The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer. Biologics 4:173–185PubMed Tejani MA, Cohen RB, Mehra R (2010) The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer. Biologics 4:173–185PubMed
8.
go back to reference Fujita K, Sano D, Kimura M, Yamashita Y, Kawakami M, Ishiguro Y, Nishimura G, Matsuda H, Tsukuda M (2007) Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma. Oncol Rep 18(1):47–51PubMed Fujita K, Sano D, Kimura M, Yamashita Y, Kawakami M, Ishiguro Y, Nishimura G, Matsuda H, Tsukuda M (2007) Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma. Oncol Rep 18(1):47–51PubMed
9.
go back to reference Seiwert TY, Haraf DJ, Cohen EE, Stenson K, Witt ME, Dekker A, Kocherginsky M, Weichselbaum RR, Chen HX, Vokes EE (2008) Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J Clin Oncol 26(10):1732–1741CrossRefPubMed Seiwert TY, Haraf DJ, Cohen EE, Stenson K, Witt ME, Dekker A, Kocherginsky M, Weichselbaum RR, Chen HX, Vokes EE (2008) Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J Clin Oncol 26(10):1732–1741CrossRefPubMed
10.
go back to reference Merlano M, Russi E, Benasso M, Corvò R, Colantonio I, Vigna-Taglianti R, Vigo V, Bacigalupo A, Numico G, Crosetto N, Gasco M, Lo Nigro C, Vitiello R, Violante S, Garrone O (2010) Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study. Ann Oncol. doi:10.1093/annonc/mdq412 PubMed Merlano M, Russi E, Benasso M, Corvò R, Colantonio I, Vigna-Taglianti R, Vigo V, Bacigalupo A, Numico G, Crosetto N, Gasco M, Lo Nigro C, Vitiello R, Violante S, Garrone O (2010) Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study. Ann Oncol. doi:10.​1093/​annonc/​mdq412 PubMed
11.
go back to reference Prichard CN, Kim S, Yazici YD, Doan DD, Jasser SA, Mandal M, Myers JN (2007) Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of anaplastic thyroid carcinoma. Laryngoscope 117(4):674–679CrossRefPubMed Prichard CN, Kim S, Yazici YD, Doan DD, Jasser SA, Mandal M, Myers JN (2007) Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of anaplastic thyroid carcinoma. Laryngoscope 117(4):674–679CrossRefPubMed
12.
go back to reference Bozec A, Sudaka A, Fischel JL, Brunstein MC, Etienne-Grimaldi MC, Milano G (2008) Combined effects of bevacizumab with erlotinib and irradiation: a preclinical study on a head and neck cancer orthotopic model. Br J Cancer 99(1):93–99CrossRefPubMed Bozec A, Sudaka A, Fischel JL, Brunstein MC, Etienne-Grimaldi MC, Milano G (2008) Combined effects of bevacizumab with erlotinib and irradiation: a preclinical study on a head and neck cancer orthotopic model. Br J Cancer 99(1):93–99CrossRefPubMed
13.
go back to reference Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, Richel DJ, Voest EE, Dijkstra JR, Vink-Börger ME, Antonini NF, Mol L, van Krieken JH, Dalesio O, Punt CJ (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563–572CrossRefPubMed Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, Richel DJ, Voest EE, Dijkstra JR, Vink-Börger ME, Antonini NF, Mol L, van Krieken JH, Dalesio O, Punt CJ (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563–572CrossRefPubMed
14.
go back to reference Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27(5):672–680CrossRefPubMed Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27(5):672–680CrossRefPubMed
15.
go back to reference Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274(5286):373–376CrossRefPubMed Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274(5286):373–376CrossRefPubMed
16.
go back to reference Inoue K, Slaton JW, Perrotte P, Davis DW, Bruns CJ, Hicklin DJ, McConkey DJ, Sweeney P, Radinsky R, Dinney CP (2000) Paclitaxel enhances the effects of the anti-epidermal growth factor receptor monoclonal antibody ImClone C225 in mice with metastatic human bladder transitional cell carcinoma. Clin Cancer Res 6(12):4874–4884PubMed Inoue K, Slaton JW, Perrotte P, Davis DW, Bruns CJ, Hicklin DJ, McConkey DJ, Sweeney P, Radinsky R, Dinney CP (2000) Paclitaxel enhances the effects of the anti-epidermal growth factor receptor monoclonal antibody ImClone C225 in mice with metastatic human bladder transitional cell carcinoma. Clin Cancer Res 6(12):4874–4884PubMed
17.
go back to reference Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8CrossRefPubMed Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8CrossRefPubMed
18.
go back to reference Tol J, Koopman M, Rodenburg CJ, Cats A, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, Mol L, Antonini NF, Punt CJ (2008) A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol 19(4):734–738CrossRefPubMed Tol J, Koopman M, Rodenburg CJ, Cats A, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, Mol L, Antonini NF, Punt CJ (2008) A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol 19(4):734–738CrossRefPubMed
19.
go back to reference Cohen EE, Davis DW, Karrison TG, Seiwert TY, Wong SJ, Nattam S, Kozloff MF, Clark JI, Yan DH, Liu W, Pierce C, Dancey JE, Stenson K, Blair E, Dekker A, Vokes EE (2009) Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncol 10(3):247–257CrossRefPubMed Cohen EE, Davis DW, Karrison TG, Seiwert TY, Wong SJ, Nattam S, Kozloff MF, Clark JI, Yan DH, Liu W, Pierce C, Dancey JE, Stenson K, Blair E, Dekker A, Vokes EE (2009) Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncol 10(3):247–257CrossRefPubMed
20.
go back to reference Punt CJ, Tol J (2009) More is less—combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol 6(12):731–733CrossRefPubMed Punt CJ, Tol J (2009) More is less—combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol 6(12):731–733CrossRefPubMed
21.
go back to reference Mandpe AH, Tsung K, Norton JA (2003) Cure of an established nonimmunogenic tumor, SCC VII, with a novel interleukin 12-based immunotherapy regimen in C3H mice. Arch Otolaryngol Head Neck Surg 129(7):786–792CrossRefPubMed Mandpe AH, Tsung K, Norton JA (2003) Cure of an established nonimmunogenic tumor, SCC VII, with a novel interleukin 12-based immunotherapy regimen in C3H mice. Arch Otolaryngol Head Neck Surg 129(7):786–792CrossRefPubMed
22.
go back to reference O’Malley BW, Cope KA, Johnson CS, Schwartz MR (1997) A new immunocompetent murine model for oral cancer. Arch Otolaryngol Head Neck Surg 123(1):20–24PubMed O’Malley BW, Cope KA, Johnson CS, Schwartz MR (1997) A new immunocompetent murine model for oral cancer. Arch Otolaryngol Head Neck Surg 123(1):20–24PubMed
23.
go back to reference Khurana D, Martin EA, Kasperbauer JL, O’Malley BW Jr, Salomao DR, Chen L, Strome SE (2001) Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy. Head Neck 23(10):899–906CrossRefPubMed Khurana D, Martin EA, Kasperbauer JL, O’Malley BW Jr, Salomao DR, Chen L, Strome SE (2001) Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy. Head Neck 23(10):899–906CrossRefPubMed
24.
go back to reference Xu ZQ, Liu Y, Wang YX, Zhang W, Zhao FY (2009) Therapeutic effects of Avastin on murine hemangioendotheliaoma. Beijing Da Xue Xue Bao 41(1):105–108PubMed Xu ZQ, Liu Y, Wang YX, Zhang W, Zhao FY (2009) Therapeutic effects of Avastin on murine hemangioendotheliaoma. Beijing Da Xue Xue Bao 41(1):105–108PubMed
25.
go back to reference de Gramont A, Van Cutsem E (2005) Investigating the potential of bevacizumab in other indications: metastatic renal cell, non-small cell lung, pancreatic and breast cancer. Oncology 69(Suppl 3):46–56CrossRefPubMed de Gramont A, Van Cutsem E (2005) Investigating the potential of bevacizumab in other indications: metastatic renal cell, non-small cell lung, pancreatic and breast cancer. Oncology 69(Suppl 3):46–56CrossRefPubMed
26.
go back to reference Bruns CJ, Harbison MT, Davis DW, Portera CA, Tsan R, McConkey DJ, Evans DB, Abbruzzese JL, Hicklin DJ, Radinsky R (2006) Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 6(5):1936–1948 Bruns CJ, Harbison MT, Davis DW, Portera CA, Tsan R, McConkey DJ, Evans DB, Abbruzzese JL, Hicklin DJ, Radinsky R (2006) Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 6(5):1936–1948
27.
go back to reference Petros AM, Olejniczak ET, Fesik SW (2004) Structural biology of the Bcl-2 family of proteins. Biochim Biophys Acta 1644(2–3):83–94PubMed Petros AM, Olejniczak ET, Fesik SW (2004) Structural biology of the Bcl-2 family of proteins. Biochim Biophys Acta 1644(2–3):83–94PubMed
28.
go back to reference Adams JM, Cory S (2007) Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr Opin Immunol 19(5):488–496CrossRefPubMed Adams JM, Cory S (2007) Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr Opin Immunol 19(5):488–496CrossRefPubMed
29.
go back to reference Lalier L, Cartron PF, Juin P, Nedelkina S, Manon S, Bechinger B, Vallette FM (2007) Bax activation and mitochondrial insertion during apoptosis. Apoptosis 12(5):887–896CrossRefPubMed Lalier L, Cartron PF, Juin P, Nedelkina S, Manon S, Bechinger B, Vallette FM (2007) Bax activation and mitochondrial insertion during apoptosis. Apoptosis 12(5):887–896CrossRefPubMed
30.
go back to reference Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G (2006) Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 13(9):1423–1433CrossRefPubMed Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G (2006) Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 13(9):1423–1433CrossRefPubMed
31.
go back to reference Lobo NA, Shimono Y, Qian D, Clarke MF (2007) The biology of cancer stem cells. Annu Rev Cell Dev Biol 23:675–699CrossRefPubMed Lobo NA, Shimono Y, Qian D, Clarke MF (2007) The biology of cancer stem cells. Annu Rev Cell Dev Biol 23:675–699CrossRefPubMed
32.
go back to reference Newman JR, Helman EE, Safavy S, Zhang W, Rosenthal EL (2009) EMMPRIN expression is required for response to bevacizumab therapy in HNSCC xenografts. Cancer Lett 274(2):313–318CrossRefPubMed Newman JR, Helman EE, Safavy S, Zhang W, Rosenthal EL (2009) EMMPRIN expression is required for response to bevacizumab therapy in HNSCC xenografts. Cancer Lett 274(2):313–318CrossRefPubMed
33.
go back to reference Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26(35):5705–5712CrossRefPubMed Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26(35):5705–5712CrossRefPubMed
Metadata
Title
Investigation of the efficacy of a bevacizumab-cetuximab-cisplatin regimen in treating head and neck squamous cell carcinoma in mice
Authors
Yixiang Wang
Ling Dong
Qingwei Bi
Xiao Li
Dengcheng Wu
Xiyuan Ge
Xiaoxia Zhang
Jia Fu
Chengfei Zhang
Cunyu Wang
Shenglin Li
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Targeted Oncology / Issue 4/2010
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-010-0164-3

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