Skip to main content

Anti-angiogenic Targeting in Metastatic Colorectal Cancer Therapy

  • Living reference work entry
  • First Online:
Tumor Angiogenesis

Abstract

Angiogenesis has been identified as a hallmark of cancer. Thus, anti-angiogenic targeting has been evaluated in cancer. Colorectal cancer is one of the entities where this therapeutic principal has been most successfully introduced into the daily care of patients. Today, several anti-angiogenic drugs are approved in all lines of metastasized colorectal cancer (mCRC). In adjuvant settings, anti-angiogenic treatment did not show any benefit. In summary, still overall the benefit from anti-angiogenic treatment is modest and the identification of specific patient subgroups benefiting from this treatment is missing. Several new drugs are in development to further improve the treatment of patients with mCRC. In addition, large efforts were made to identify predictive biomarker, but so far, none of these has entered the clinical routine. Here we present the current status of anti-angiogenic drugs in mCRC and the new drugs in development for this clinical entity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Bendell JC, Bekaii-Saab TS, Cohn AL et al (2012) Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist 17:1486–1495. doi:10.1634/theoncologist.2012-0190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennouna J, Sastre J, Arnold D et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37. doi:10.1016/S1470-2045(12)70477-1

    Article  CAS  PubMed  Google Scholar 

  • Benson AB, Kiss I, Bridgewater J et al (2016) BATON-CRC: a phase II randomized trial comparing tivozanib plus mFOLFOX6 with bevacizumab plus mFOLFOX6 in stage IV metastatic colorectal cancer. Clin Cancer Res. doi:10.1158/1078-0432.CCR-15-3117

    PubMed  Google Scholar 

  • Cabebe EC, Fisher GA, Sikic BI (2012) A phase I trial of vandetanib combined with capecitabine, oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer. Investig New Drugs 30:1082–1087. doi:10.1007/s10637-011-9656-y

    Article  CAS  Google Scholar 

  • Cao Y (2009) Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal 2:re1. doi:10.1126/scisignal.259re1

    Article  PubMed  Google Scholar 

  • Cao J, Zhang J, Peng W et al (2016) A phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors. Cancer Chemother Pharmacol 78:259–269. doi:10.1007/s00280-016-3069-8

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Jain RK (2011) Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10:417–427. doi:10.1038/nrd3455

    Article  CAS  PubMed  Google Scholar 

  • Cremolini C, Loupakis F, Antoniotti C et al (2015a) FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol 16:1306–1315. doi:10.1016/S1470-2045(15)00122-9

    Article  CAS  PubMed  Google Scholar 

  • Cremolini C, Schirripa M, Antoniotti C et al (2015b) First-line chemotherapy for mCRC—a review and evidence-based algorithm. Nat Rev Clin Oncol 12:607–619. doi:10.1038/nrclinonc.2015.129

    Article  CAS  PubMed  Google Scholar 

  • Cunningham D, Láng I, Marcuello E et al (2013a) Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14:1077–1085. doi:10.1016/S1470-2045(13)70154-2

    Article  CAS  PubMed  Google Scholar 

  • Cunningham D, Wong RPW, D'Haens G et al (2013b) Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer. Br J Cancer 108:493–502. doi:10.1038/bjc.2012.545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Díaz-Rubio E, Gómez-España A, Massuti B et al (2012) First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 17:15–25. doi:10.1634/theoncologist.2011-0249

    Article  PubMed  PubMed Central  Google Scholar 

  • Douillard JY, Cunningham D, Roth AD et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047

    Article  CAS  PubMed  Google Scholar 

  • Falcone A, Ricci S, Brunetti I et al (2007) 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 25:1670–1676. doi:10.1200/JCO.2006.09.0928

    Article  CAS  PubMed  Google Scholar 

  • Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403. doi:10.1016/j.ejca.2012.12.027

    Article  CAS  PubMed  Google Scholar 

  • Folprecht G, Pericay C, Saunders MP et al (2016) Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol 27:1273–1279. doi:10.1093/annonc/mdw176

    Article  CAS  PubMed  Google Scholar 

  • Fontanella C, Ongaro E, Bolzonello S et al (2014) Clinical advances in the development of novel VEGFR2 inhibitors. Ann Transl Med 2:123. doi:10.3978/j.issn.2305-5839.2014.08.14

    PubMed  PubMed Central  Google Scholar 

  • Gaya A, Tse V (2012) A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev 38:484–493. doi:10.1016/j.ctrv.2011.12.008

    Article  CAS  PubMed  Google Scholar 

  • Giampieri R, Caporale M, Pietrantonio F et al (2016) Second-line angiogenesis inhibition in metastatic colorectal cancer patients: straightforward or overcrowded? Crit Rev Oncol Hematol 100:99–106. doi:10.1016/j.critrevonc.2016.02.005

    Article  PubMed  Google Scholar 

  • Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) 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 25:1539–1544. doi:10.1200/JCO.2006.09.6305

    Article  CAS  PubMed  Google Scholar 

  • Goel S, Wong AH-K, Jain RK (2012) Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease. Cold Spring Harb Perspect Med 2:a006486. doi:10.1101/cshperspect.a006486

    Article  PubMed  PubMed Central  Google Scholar 

  • de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947

    Article  PubMed  Google Scholar 

  • Grothey A, Sugrue MM, Purdie DM et al (2008) 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 26:5326–5334. doi:10.1200/JCO.2008.16.3212

    Article  CAS  PubMed  Google Scholar 

  • Grothey A, Van Cutsem E, Sobrero A et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303–312. doi:10.1016/S0140-6736(12)61900-X

    Article  CAS  PubMed  Google Scholar 

  • Gruenberger T, Bridgewater J, Chau I, Garcia Alfonso P et al (2015) Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol 26:702–708. doi:10.1093/annonc/mdu580

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70. doi:10.1016/S0092-8674(00)81683-9

    Article  CAS  PubMed  Google Scholar 

  • Hecht JR, Trarbach T, Hainsworth JD et al (2011) Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 29:1997–2003. doi:10.1200/JCO.2010.29.4496

    Article  CAS  PubMed  Google Scholar 

  • Hegewisch-Becker S, Graeven U, Lerchenmüller CA et al (2015) Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 16:1355–1369. doi:10.1016/S1470-2045(15)00042-X

    Article  CAS  PubMed  Google Scholar 

  • Heldin C-H (2013) Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal 11:97. doi:10.1186/1478-811X-11-97

    Article  PubMed  PubMed Central  Google Scholar 

  • Hochster HS, Grothey A, Hart L et al (2014) Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT. Ann Oncol 25:1172–1178. doi:10.1093/annonc/mdu107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoff PM, Hochhaus A, Pestalozzi BC et al (2012) Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). J Clin Oncol 30:3596–3603. doi:10.1200/JCO.2012.42.6031

    Article  CAS  PubMed  Google Scholar 

  • Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342. doi:10.1056/NEJMoa032691

    Article  CAS  PubMed  Google Scholar 

  • Iwamoto S, Takahashi T, Tamagawa H et al (2015) FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study. Ann Oncol 26:1427–1433. doi:10.1093/annonc/mdv197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kabbinavar F, Hurwitz HI, Fehrenbacher L et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65

    Article  CAS  PubMed  Google Scholar 

  • Kabbinavar FF, Schulz J, McCleod M et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23:3697–3705. doi:10.1200/JCO.2005.05.112

    Article  CAS  PubMed  Google Scholar 

  • Li J, Qin S, Xu R et al (2015a) Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 16:619–629. doi:10.1016/S1470-2045(15)70156-7

    Article  CAS  PubMed  Google Scholar 

  • Li J, Xu R, Bai Y et al (2015b) A randomized, double-blind, placebo-controlled, multicenter phase II clinical trial of fruquintinib in patients with metastatic colorectal cancer (mCRC). Eur J Cancer 51:S366

    Article  Google Scholar 

  • Loupakis F, Cremolini C, Masi G et al (2014) Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 371:1609–1618. doi:10.1056/NEJMoa1403108

    Article  PubMed  Google Scholar 

  • Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60

    Article  CAS  PubMed  Google Scholar 

  • Masi G, Loupakis F, Salvatore L et al (2010) Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol 11:845–852. doi:10.1016/S1470-2045(10)70175-3

    Article  CAS  PubMed  Google Scholar 

  • Masi G, Salvatore L, Boni L et al (2015) Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol 26:724–730. doi:10.1093/annonc/mdv012

    Article  CAS  PubMed  Google Scholar 

  • Meyerhardt JA, Ancukiewicz M, Abrams TA et al (2012) Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) as therapy for patients with previously treated metastastic colorectal cancer. PLoS One 7:e38231. doi:10.1371/journal.pone.0038231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura Y, Tanaka F, Yoshikawa Y et al (2008) PDGF-BB is a novel prognostic factor in colorectal cancer. Ann Surg Oncol 15:2129–2136. doi:10.1245/s10434-008-9943-9

    Article  PubMed  Google Scholar 

  • Oldenhuis CN, Loos WJ, Esteves B et al (2015) A phase Ib study of the VEGF receptor tyrosine kinase inhibitor tivozanib and modified FOLFOX-6 in patients with advanced gastrointestinal malignancies. Clin Colorectal Cancer 14:18–24.e1. doi:10.1016/j.clcc.2014.12.001

    Article  PubMed  Google Scholar 

  • O'Neil BH, Cainap C, Van Cutsem E et al (2014) Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer. Clin Colorectal Cancer 13:156–163.e2. doi:10.1016/j.clcc.2014.04.001

    Article  PubMed  Google Scholar 

  • Passardi A, Nanni O, Tassinari D et al (2015) Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial. Ann Oncol 26:1201–1207. doi:10.1093/annonc/mdv130

    Article  CAS  PubMed  Google Scholar 

  • Peeters M, Strickland AH, Lichinitser M et al (2013) A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma. Br J Cancer 108:503–511. doi:10.1038/bjc.2012.594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Price TJ et al (2012) Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C. Ann Oncol 23:1531–1536

    Google Scholar 

  • Saltz LB, Cox JV, Blanke C et al (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan study group. N Engl J Med 343:905–914. doi:10.1056/NEJM200009283431302

    Article  CAS  PubMed  Google Scholar 

  • Saltz LB, Clarke S, Díaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019. doi:10.1200/JCO.2007.14.9930

    Article  CAS  PubMed  Google Scholar 

  • Satoh T, Yamaguchi K, Boku N et al (2012) Phase I results from a two-part phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer. Investig New Drugs 30:1511–1518. doi:10.1007/s10637-011-9693-6

    Article  CAS  Google Scholar 

  • Schmoll H-J, Cunningham D, Sobrero A et al (2012) Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III). J Clin Oncol 30:3588–3595. doi:10.1200/JCO.2012.42.5355

    Article  CAS  PubMed  Google Scholar 

  • Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64:104–117. doi:10.3322/caac.21220

    Article  PubMed  Google Scholar 

  • Simkens LHJ, van Tinteren H, May A et al (2015) Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 385:1843–1852. doi:10.1016/S0140-6736(14)62004-3

    Article  CAS  PubMed  Google Scholar 

  • Siu LL, Shapiro JD, Jonker DJ et al (2013) Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 trial. J Clin Oncol 31:2477–2484. doi:10.1200/JCO.2012.46.0543

    Article  CAS  PubMed  Google Scholar 

  • Sobrero AF, Bruzzi P (2011) Vatalanib in advanced colorectal cancer: two studies with identical results. J Clin Oncol 29:1938–1940. doi:10.1200/JCO.2010.33.2429

    Article  CAS  PubMed  Google Scholar 

  • Spratlin JL, Cohen RB, Eadens M et al (2010) Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 28:780–787. doi:10.1200/JCO.2009.23.7537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tabernero J, Van Cutsem E, Lakomy R et al (2014) Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer 50:320–331. doi:10.1016/j.ejca.2013.09.013

    Article  CAS  PubMed  Google Scholar 

  • Tabernero J, Yoshino T, Cohn AL et al (2015) Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 16:499–508. doi:10.1016/S1470-2045(15)70127-0

    Article  CAS  PubMed  Google Scholar 

  • Tampellini M, Sonetto C, Scagliotti GV (2016) Novel anti-angiogenic therapeutic strategies in colorectal cancer. Expert Opin Investig Drugs 25:507–520. doi:10.1517/13543784.2016.1161754

    Article  CAS  PubMed  Google Scholar 

  • Tang PA, Cohen SJ, Kollmannsberger C et al (2012) Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer. Clin Cancer Res 18:6023–6031. doi:10.1158/1078-0432.CCR-11-3252

    Article  CAS  PubMed  Google Scholar 

  • Tebbutt NC, Wilson K, Gebski VJ et al (2010) 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 28:3191–3198. doi:10.1200/JCO.2009.27.7723

    Article  CAS  PubMed  Google Scholar 

  • Tebbutt N, Kotasek D, Burris HA et al (2015) Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol 75:993–1004. doi:10.1007/s00280-015-2694-y

    Article  CAS  PubMed  Google Scholar 

  • Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. doi:10.3322/caac.21262

    Article  PubMed  Google Scholar 

  • Tournigand C, Chibaudel B, Samson B et al (2015) Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol 16:1493–1505. doi:10.1016/S1470-2045(15)00216-8

    Article  CAS  PubMed  Google Scholar 

  • Tung JJ, Tattersall IW, Kitajewski J (2012) Tips, stalks, tubes: notch-mediated cell fate determination and mechanisms of tubulogenesis during angiogenesis. Cold Spring Harb Perspect Med 2:a006601. doi:10.1101/cshperspect.a006601

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Cutsem E, Twelves C, Cassidy J et al (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19:4097–4106

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Bajetta E, Valle J et al (2011) Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 29:2004–2010. doi:10.1200/JCO.2010.29.5436

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Tabernero J, Lakomy R et al (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499–3506. doi:10.1200/JCO.2012.42.8201

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Khayat D, Verslype C et al (2013) Phase I dose-escalation study of intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours. Eur J Cancer 49:17–24. doi:10.1016/j.ejca.2012.07.007

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Prenen H, D'Haens G et al (2015) A phase I/II, open-label, randomised study of nintedanib plus mFOLFOX6 versus bevacizumab plus mFOLFOX6 in first-line metastatic colorectal cancer patients. Ann Oncol 26:2085–2091. doi:10.1093/annonc/mdv286

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Cervantes A, Adam R et al (2016a) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422. doi:10.1093/annonc/mdw235

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Joulain F, Hoff PM et al (2016b) Aflibercept plus FOLFIRI vs. placebo plus FOLFIRI in second-line metastatic colorectal cancer: a post hoc analysis of survival from the phase III VELOUR study subsequent to exclusion of patients who had recurrence during or within 6 months of completing adjuvant Oxaliplatin-based therapy. Target Oncol 11:383–400. doi:10.1007/s11523-015-0402-9

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Yoshino T, Hocke J et al (2016c) Rationale and design for the LUME-Colon 1 study: a randomized, double-blind, placebo-controlled phase III trial of Nintedanib plus best supportive care versus placebo plus best supportive Care in Patients with advanced colorectal cancer refractory to standard treatment. Clin Colorectal Cancer 15:91–94.e1. doi:10.1016/j.clcc.2015.09.005

    Article  PubMed  Google Scholar 

  • Van de Veire S, Stalmans I, Heindryckx F et al (2010) Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell 141:178–190. doi:10.1016/j.cell.2010.02.039

    Article  PubMed  Google Scholar 

  • Willett CG, Boucher Y, di Tomaso E et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147. doi:10.1038/nm988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winkler F, Kozin SV, Tong RT et al (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563. doi:10.1016/j.ccr.2004.10.011

    CAS  PubMed  Google Scholar 

  • Wong R, Cunningham D, Barbachano Y et al (2011) A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol 22:2042–2048. doi:10.1093/annonc/mdq714

    Article  CAS  PubMed  Google Scholar 

  • Xu R, Shen L, Wang K et al (2015) A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer. J Clin Oncol 33:513

    Article  CAS  Google Scholar 

  • Yao J, Wu X, Zhuang G et al (2011) Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci USA 108:11590–11595. doi:10.1073/pnas.1109029108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou A, Zhang W, Chang C et al (2013) Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib. Cancer Chemother Pharmacol 72:1043–1053. doi:10.1007/s00280-013-2282-y

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Zander .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Zander, T., Goede, V., Hallek, M. (2017). Anti-angiogenic Targeting in Metastatic Colorectal Cancer Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_16-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-31215-6_16-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-31215-6

  • Online ISBN: 978-3-319-31215-6

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics