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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Review Article

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Author(s): Wen-Cong Ruan, Yue-Ping Che, Li Ding and Hai-Feng Li*

Volume 21, Issue 10, 2018

Page: [718 - 724] Pages: 7

DOI: 10.2174/1386207322666190119162352

Price: $65

Abstract

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer.

Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC.

Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy.

Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy.

Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

Keywords: Bevacizumab, metastatic colorectal cancer (mCRC), second-line treatment, overall survival (OS), progression-free survival (PFS), meta-analysis.

[1]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[2]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[3]
Jemal, A.; Siegel, R.; Xu, J.; Ward, E. Cancer statistics, 2010. CA Cancer J. Clin., 2010, 60(5), 277-300.
[4]
Van Cutsem, E.; Nordlinger, B.; Adam, R.; Köhne, C-H.; Pozzo, C.; Poston, G.; Ychou, M.; Rougier, P. European Colorectal Metastases Treatment, G. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur. J. Cancer, 2006, 42(14), 2212-2221.
[5]
Grothey, A. Is there a third-line therapy for metastatic colorectal cancer? Semin. Oncol., 2006, 33(6)(Suppl. 11), S36-S38.
[6]
Wu, D-M.; Wang, Y-J.; Fan, S-H.; Zhuang, J.; Zhang, Z-F.; Shan, Q.; Han, X-R.; Wen, X.; Li, M-Q.; Hu, B.; Sun, C-H.; Bao, Y-X.; Xiao, H-J.; Yang, L.; Lu, J.; Zheng, Y-L. Network meta-analysis of the efficacy of first-line chemotherapy regimens in patients with advanced colorectal cancer. Oncotarget, 2017, 8, 100668-100677.
[7]
Kirstein, M.M.; Lange, A.; Prenzler, A.; Manns, M.P.; Kubicka, S.; Vogel, A. Targeted therapies in metastatic colorectal cancer: A systematic review and assessment of currently available data. Oncologist, 2014, 19(11), 1156-1168.
[8]
Marques, A.M.; Turner, A.; de Mello, R.A. Personalizing medicine for metastatic colorectal cancer: current developments. World J. Gastroenterol., 2014, 20(30), 10425-10431.
[9]
Arnold, D.; Stein, A. New developments in the second-line treatment of metastatic colorectal cancer: Potential place in therapy. Drugs, 2013, 73(9), 883-891.
[10]
Cunningham, D.; Atkin, W.; Lenz, H-J.; Lynch, H.T.; Minsky, B.; Nordlinger, B.; Starling, N. Colorectal cancer. Lancet, 2010, 375(9719), 1030-1047.
[11]
Goldberg, R.M. Therapy for metastatic colorectal cancer. Oncologist, 2006, 11(9), 981-987.
[12]
Gustavsson, B.; Carlsson, G.; Machover, D.; Petrelli, N.; Roth, A.; Schmoll, H-J.; Tveit, K-M.; Gibson, F. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin. Colorectal Cancer, 2015, 14(1), 1-10.
[13]
Rougier, P.; Lepere, C. Second-line treatment of patients with metastatic colorectal cancer. Semin. Oncol., 2005, 32(6)(Suppl. 9), S48-S54.
[14]
Seiwert, T.Y.; Haraf, D.J.; Cohen, E.E.W.; Stenson, K.; Witt, M.E.; Dekker, A.; Kocherginsky, M.; Weichselbaum, R.R.; Chen, H.X.; Vokes, E.E. Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J. Clin. Oncol., 2008, 26(10), 1732-1741.
[15]
Okita, N.T.; Esaki, T.; Baba, E.; Sakai, D.; Tokunaga, S.; Takiuchi, H.; Mizunuma, N.; Nagashima, K.; Kato, K. A multicenter phase II study of the stop-and-go modified FOLFOX6 with bevacizumab for first-line treatment of patients with metastatic colorectal cancer. Invest. New Drugs, 2012, 30(5), 2026-2031.
[16]
Hurwitz, H.; Fehrenbacher, L.; Novotny, W.; Cartwright, T.; Hainsworth, J.; Heim, W.; Berlin, J.; Baron, A.; Griffing, S.; Holmgren, E.; Ferrara, N.; Fyfe, G.; Rogers, B.; Ross, R.; Kabbinavar, F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med., 2004, 350(23), 2335-2342.
[17]
Saltz, L.B.; Clarke, S.; Díaz-Rubio, E.; Scheithauer, W.; Figer, A.; Wong, R.; Koski, S.; Lichinitser, M.; Yang, T-S.; Rivera, F.; Couture, F.; Sirzén, F.; Cassidy, J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J. Clin. Oncol., 2008, 26(12), 2013-2019.
[18]
Hess, G.P.; Wang, P.F.; Quach, D.; Barber, B.; Zhao, Z. Systemic therapy for metastatic colorectal cancer: Patterns of chemotherapy and biologic therapy use in US medical oncology practice. J. Oncol. Pract., 2010, 6(6), 301-307.
[19]
Giantonio, B.J.; Catalano, P.J.; Meropol, N.J.; O’Dwyer, P.J.; Mitchell, E.P.; Alberts, S.R.; Schwartz, M.A.; Benson, A.B. Eastern Cooperative Oncology Group Study, E. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200. J. Clin. Oncol., 2007, 25(12), 1539-1544.
[20]
Roqué, I.; Figuls, M.; Solà, I.; Martin-Richard, M.; López, J-J.; Bonfill Cosp, X. Second-line chemotherapy in advanced and metastatic CRC. Cochrane Database Syst. Rev., 2009, CD006875.
[21]
Sørbye, H.; Berglund, A.; Tveit, K.M.; Ogreid, D.; Wanderås, E.H.; Wentzel-Larsen, T.; Dahl, O.; Glimelius, B. Secondary treatment and predictive factors for second-line chemotherapy after first-line oxaliplatin-based therapy in metastatic colorectal cancer. Acta Oncol., 2007, 46(7), 982-988.
[22]
Tierney, J.F.; Stewart, L.A.; Ghersi, D.; Burdett, S.; Sydes, M.R. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8, 16.
[23]
Higgins, J.P.T.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med., 2002, 21(11), 1539-1558.
[24]
Higgins, J.P.T.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414), 557-560.
[25]
Hecht, J.R.; Cohn, A.; Dakhil, S.; Saleh, M.; Piperdi, B.; Cline-Burkhardt, M.; Tian, Y.; Go, W.Y. SPIRITT: A randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as second-line treatment in patients with unresectable wild type KRAS metastatic colorectal cancer. Clin. Colorectal Cancer, 2015, 14(2), 72-80.
[26]
Bennouna, J.; Sastre, J.; Arnold, D.; Österlund, P.; Greil, R.; Van Cutsem, E.; von Moos, R.; Viéitez, J.M.; Bouché, O.; Borg, C.; Steffens, C-C.; Alonso-Orduña, V.; Schlichting, C.; Reyes-Rivera, I.; Bendahmane, B.; André, T.; Kubicka, S.; Investigators, M.L.S. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): A randomised phase 3 trial. Lancet Oncol., 2013, 14(1), 29-37.
[27]
Cao, R.; Zhang, S.; Ma, D.; Hu, L. A multi-center randomized phase II clinical study of bevacizumab plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) compared with FOLFIRI alone as second-line treatment for Chinese patients with metastatic colorectal cancer. Med. Oncol., 2015, 32(1), 325.
[28]
Masi, G.; Salvatore, L.; Boni, L.; Loupakis, F.; Cremolini, C.; Fornaro, L.; Schirripa, M.; Cupini, S.; Barbara, C.; Safina, V.; Granetto, C.; Fea, E.; Antonuzzo, L.; Boni, C.; Allegrini, G.; Chiara, S.; Amoroso, D.; Bonetti, A.; Falcone, A.; Investigators, B.S. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: Final results of the randomized BEBYP trial. Ann. Oncol., 2015, 26(4), 724-730.
[29]
Goldberg, R.M.; Sargent, D.J.; Morton, R.F.; Fuchs, C.S.; Ramanathan, R.K.; Williamson, S.K.; Findlay, B.P.; Pitot, H.C.; Alberts, S.R. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J. Clin. Oncol., 2004, 22(1), 23-30.
[30]
Cassidy, J.; Clarke, S.; Díaz-Rubio, E.; Scheithauer, W.; Figer, A.; Wong, R.; Koski, S.; Lichinitser, M.; Yang, T-S.; Rivera, F.; Couture, F.; Sirzén, F.; Saltz, L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J. Clin. Oncol., 2008, 26(12), 2006-2012.
[31]
Falcone, A.; Ricci, S.; Brunetti, I.; Pfanner, E.; Allegrini, G.; Barbara, C.; Crinò, L.; Benedetti, G.; Evangelista, W.; Fanchini, L.; Cortesi, E.; Picone, V.; Vitello, S.; Chiara, S.; Granetto, C.; Porcile, G.; Fioretto, L.; Orlandini, C.; Andreuccetti, M.; Masi, G.; Gruppo Oncologico Nord, O. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: The Gruppo Oncologico Nord Ovest. J. Clin. Oncol., 2007, 25(13), 1670-1676.
[32]
Welch, S.; Spithoff, K.; Rumble, R.B.; Maroun, J. Gastrointestinal Cancer Disease Site, G. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: A systematic review. Ann. Oncol., 2010, 21(6), 1152-1162.
[33]
Bokemeyer, C.; Bondarenko, I.; Makhson, A.; Hartmann, J.T.; Aparicio, J.; de Braud, F.; Donea, S.; Ludwig, H.; Schuch, G.; Stroh, C.; Loos, A.H.; Zubel, A.; Koralewski, P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol., 2009, 27(5), 663-671.
[34]
Douillard, J-Y.; Siena, S.; Cassidy, J.; Tabernero, J.; Burkes, R.; Barugel, M.; Humblet, Y.; Bodoky, G.; Cunningham, D.; Jassem, J.; Rivera, F.; Kocákova, I.; Ruff, P.; Błasińska-Morawiec, M.; Šmakal, M.; Canon, J-L.; Rother, M.; Oliner, K.S.; Wolf, M.; Gansert, J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J. Clin. Oncol., 2010, 28(31), 4697-4705.
[35]
Peeters, M.; Price, T.J.; Cervantes, A.; Sobrero, A.F.; Ducreux, M.; Hotko, Y.; André, T.; Chan, E.; Lordick, F.; Punt, C.J.A.; Strickland, A.H.; Wilson, G.; Ciuleanu, T-E.; Roman, L.; Van Cutsem, E.; Tzekova, V.; Collins, S.; Oliner, K.S.; Rong, A.; Gansert, J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J. Clin. Oncol., 2010, 28(31), 4706-4713.
[36]
Cohn, A.L.; Tabernero, J.; Maurel, J.; Nowara, E.; Sastre, J.; Chuah, B.Y.S.; Kopp, M.V.; Sakaeva, D.D.; Mitchell, E.P.; Dubey, S.; Suzuki, S.; Hei, Y.J.; Galimi, F.; McCaffery, I.; Pan, Y.; Loberg, R.; Cottrell, S.; Choo, S.P. A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer. Ann. Oncol., 2013, 24(7), 1777-1785.
[37]
van Geelen, C.M.; Westra, J.L.; de Vries, E.G.; Boersma-van Ek, W.; Zwart, N.; Hollema, H.; Boezen, H.M.; Mulder, N.H.; Plukker, J.T.; de Jong, S.; Kleibeuker, J.H.; Koornstra, J.J. Prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand and its receptors in adjuvantly treated stage III colon cancer patients. J. Clin. Oncol., 2006, 24(31), 4998-5004.
[38]
Hakam, A.; Yeatman, T.J.; Lu, L.; Mora, L.; Marcet, G.; Nicosia, S.V.; Karl, R.C.; Coppola, D. Expression of insulin-like growth factor-1 receptor in human colorectal cancer. Hum. Pathol., 1999, 30(10), 1128-1133.
[39]
Ishigami, S.I.; Arii, S.; Furutani, M.; Niwano, M.; Harada, T.; Mizumoto, M.; Mori, A.; Onodera, H.; Imamura, M. Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer. Br. J. Cancer, 1998, 78(10), 1379-1384.
[40]
Bergers, G.; Benjamin, L.E. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer, 2003, 3(6), 401-410.
[41]
Loupakis, F.; Bria, E.; Vaccaro, V.; Cuppone, F.; Milella, M.; Carlini, P.; Cremolini, C.; Salvatore, L.; Falcone, A.; Muti, P.; Sperduti, I.; Giannarelli, D.; Cognetti, F. Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: Meta-analysis of randomized clinical trials. J. Exp. Clin. Cancer Res., 2010, 29, 58.
[42]
Tebbutt, N.C.; Wilson, K.; Gebski, V.J.; Cummins, M.M.; Zannino, D.; van Hazel, G.A.; Robinson, B.; Broad, A.; Ganju, V.; Ackland, S.P.; Forgeson, G.; Cunningham, D.; Saunders, M.P.; Stockler, M.R.; Chua, Y.; Zalcberg, J.R.; Simes, R.J.; Price, T.J. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J. Clin. Oncol., 2010, 28(19), 3191-3198.
[43]
Mellor, H.R.; Callaghan, R. Resistance to chemotherapy in cancer: a complex and integrated cellular response. Pharmacology, 2008, 81(4), 275-300.
[44]
Bergers, G.; Hanahan, D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer, 2008, 8(8), 592-603.
[45]
Giantonio, B.J. Targeted therapies: Goldie-Coldman and bevacizumab beyond disease progression. Nat. Rev. Clin. Oncol., 2009, 6(6), 311-312.

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