Skip to main content

Advertisement

SpringerLink
Log in

Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit

  • Colorectal Cancer Hepatic Metastases (MA Choti, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Liver metastases are a frequent and commonly lethal complication of colorectal cancer. Surgical resection of limited liver disease offers currently the best chance of long-term survival, but surgery is not feasible for a rather significant proportion of patients with hepatic metastases. Despite the overall improvement in the medical management of patients with metastatic colorectal cancer, whose median survival has been substantially prolonged with the availability of novel drugs, long-term outcomes remain rather poor if a combined onco-surgical strategy cannot be implemented. Nonetheless, newer chemotherapy schedules have become more frequently, rapidly and deeply active, improving hepatic lesions’ downsizing, hence extending the pool of patients amenable to secondary liver surgery. Here, we summarize available data on the efficacy and safety of bevacizumab, an anti-VEGF monoclonal antibody indicated for the treatment of metastatic colorectal cancer, as a conversion chemotherapeutic option in the management of patients with liver metastases.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest have been highlighted as: • Of importance

  1. Morris EJ et al. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg. 2010;97(7):1110–8.

    Article  CAS  PubMed  Google Scholar 

  2. Ferrara N et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400.

    Article  CAS  PubMed  Google Scholar 

  3. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182–6. Landmark overview of the concept of anti-angiogenic therapy in cancer.

    Article  CAS  PubMed  Google Scholar 

  4. Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun. 2005;333(2):328–35.

    Article  CAS  PubMed  Google Scholar 

  5. Gasparini G et al. Angiogenic inhibitors: a new therapeutic strategy in oncology. Nat Clin Pract Oncol. 2005;2(11):562–77.

    Article  CAS  PubMed  Google Scholar 

  6. Bennouna J et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14(1):29–37.

    Article  CAS  PubMed  Google Scholar 

  7. Giantonio BJ et al. 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):1539–44.

    Article  CAS  PubMed  Google Scholar 

  8. Hurwitz H et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.

    Article  CAS  PubMed  Google Scholar 

  9. Diaz-Rubio E et al. 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. 2012;17(1):15–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Simkens LH et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015;385(9980):1843–52.

    Article  CAS  PubMed  Google Scholar 

  11. Tournigand C, et al. 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. 2015.

  12. Petrelli F et al. FOLFIRI-bevacizumab as first-line chemotherapy in 3500 patients with advanced colorectal cancer: a pooled analysis of 29 published trials. Clin Colorectal Cancer. 2013;12(3):145–51.

    Article  CAS  PubMed  Google Scholar 

  13. Beretta GD et al. FOLFIRI + bevacizumab as second-line therapy for metastatic colorectal cancer pretreated with oxaliplatin: a pooled analysis of published trials. Med Oncol. 2013;30(1):486.

    Article  PubMed  Google Scholar 

  14. Petrelli F et al. Efficacy of oxaliplatin-based chemotherapy + bevacizumab as first-line treatment for advanced colorectal cancer: a systematic review and pooled analysis of published trials. Am J Clin Oncol. 2015;38(2):227–33.

    Article  CAS  PubMed  Google Scholar 

  15. Hurwitz HI et al. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013;18(9):1004–12.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Loupakis F et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.

    Article  PubMed  Google Scholar 

  17. Gruenberger T et al. 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. 2015;26(4):702–8.

    Article  CAS  PubMed  Google Scholar 

  18. Garcia-Alfonso P, et al. Neoadjuvant and conversion treatment of patients with colorectal liver metastasis: the potential role of bevacizumab and other antiangiogenic agents. Target Oncol. 2015;10(4):453–65. doi:10.1007/s11523-015-0362-0.

  19. de Haas RJ et al. Impact of expanding criteria for resectability of colorectal metastases on short- and long-term outcomes after hepatic resection. Ann Surg. 2011;253(6):1069–79.

    Article  PubMed  Google Scholar 

  20. Adam R et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240(6):1052–61. discussion 1061-4.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Vigano L et al. Progression while receiving preoperative chemotherapy should not be an absolute contraindication to liver resection for colorectal metastases. Ann Surg Oncol. 2012;19(9):2786–96.

    Article  PubMed  Google Scholar 

  22. Adam R et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol. 2001;8(4):347–53. First documentation of long-term survival in patients with metastatic colorectal cancer following medico-surgical strategy.

    Article  CAS  PubMed  Google Scholar 

  23. Adam R et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol. 2009;27(11):1829–35.

    Article  PubMed  Google Scholar 

  24. Qu CY et al. Value of bevacizumab in treatment of colorectal cancer: a meta-analysis. World J Gastroenterol. 2015;21(16):5072–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Poston GJ et al. OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol. 2005;23(28):7125–34.

    Article  PubMed  Google Scholar 

  26. Nordlinger B et al. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol. 2009;20(6):985–92.

    Article  CAS  PubMed  Google Scholar 

  27. Adam R et al. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist. 2012;17(10):1225–39. Expert view of an efficient and meaningful onco-surgical approach.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Takatsuki M et al. Evaluation of resectability after neoadjuvant chemotherapy for primary non-resectable colorectal liver metastases: a multicenter study. Eur J Surg Oncol. 2016;42(2):184–9.

    Article  CAS  PubMed  Google Scholar 

  29. Uetake H et al. A multicenter phase II trial of mFOLFOX6 plus bevacizumab to treat liver-only metastases of colorectal cancer that are unsuitable for upfront resection (TRICC0808). Ann Surg Oncol. 2015;22(3):908–15.

    Article  PubMed  Google Scholar 

  30. Beppu T et al. Liver resectability of advanced liver-limited colorectal liver metastases following mFOLFOX6 with bevacizumab (KSCC0802 Study). Anticancer Res. 2014;34(11):6655–62.

    CAS  PubMed  Google Scholar 

  31. Bruera G et al. Effectiveness of liver metastasectomies in patients with metastatic colorectal cancer treated with FIr-B/FOx triplet chemotherapy plus bevacizumab. Clin Colorectal Cancer. 2012;11(2):119–26.

    Article  CAS  PubMed  Google Scholar 

  32. Pietrantonio F et al. Bevacizumab-based neoadjuvant chemotherapy for colorectal cancer liver metastases: Pitfalls and helpful tricks in a review for clinicians. Crit Rev Oncol Hematol. 2015;95(3):272–81.

    Article  PubMed  Google Scholar 

  33. Wong R et al. 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. 2011;22(9):2042–8.

    Article  CAS  PubMed  Google Scholar 

  34. Cremolini C et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol. 2015;26(6):1188–94.

    Article  CAS  PubMed  Google Scholar 

  35. Lehmann K et al. Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg. 2012;255(2):237–47.

    Article  PubMed  Google Scholar 

  36. Gruenberger T, Arnold D, Rubbia-Brandt L. Pathologic response to bevacizumab-containing chemotherapy in patients with colorectal liver metastases and its correlation with survival. Surg Oncol. 2012;21(4):309–15.

    Article  CAS  PubMed  Google Scholar 

  37. Vigano L et al. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. Ann Surg. 2013;258(5):731–40. discussion 741-2.

    Article  PubMed  Google Scholar 

  38. Blazer 3rd DG et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26(33):5344–51.

    Article  PubMed  Google Scholar 

  39. Rubbia-Brandt L et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007;18(2):299–304.

    Article  CAS  PubMed  Google Scholar 

  40. Adam R et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol. 2008;26(10):1635–41.

    Article  PubMed  Google Scholar 

  41. van Vledder MG et al. Disappearing colorectal liver metastases after chemotherapy: should we be concerned? J Gastrointest Surg. 2010;14(11):1691–700.

    Article  PubMed  Google Scholar 

  42. Kishi Y et al. Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2010;17(11):2870–6.

    Article  PubMed  Google Scholar 

  43. Ribero D et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007;110(12):2761–7.

    Article  PubMed  Google Scholar 

  44. Klinger M et al. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol. 2010;17(8):2059–65.

    Article  PubMed  Google Scholar 

  45. Pietrantonio F et al. Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases. Med Oncol. 2015;32(7):182.

    Article  PubMed  Google Scholar 

  46. Constantinidou A et al. Perioperative chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer undergoing liver resection. Clin Colorectal Cancer. 2013;12(1):15–22.

    Article  CAS  PubMed  Google Scholar 

  47. Carrasco J, et al. Pathological responses after angiogenesis or EGFR inhibitors in metastatic colorectal cancer depend on the chemotherapy backbone. Br J Cancer. 2015;113(9):1298–304. doi:10.1038/bjc.2015.321.

  48. Vera R et al. Retrospective analysis of pathological response in colorectal cancer liver metastases following treatment with bevacizumab. Clin Transl Oncol. 2014;16(8):739–45.

    Article  CAS  PubMed  Google Scholar 

  49. Chang HH et al. Infarct-like necrosis: a distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. Am J Surg Pathol. 2012;36(4):570–6.

    Article  PubMed  Google Scholar 

  50. Benoist S et al. Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol. 2006;24(24):3939–45.

    Article  PubMed  Google Scholar 

  51. Elias D et al. Outcome of posthepatectomy-missing colorectal liver metastases after complete response to chemotherapy: impact of adjuvant intra-arterial hepatic oxaliplatin. Ann Surg Oncol. 2007;14(11):3188–94.

    Article  PubMed  Google Scholar 

  52. Scott LJ et al. Systemic safety of anti-VEGF drugs: a commentary. Expert Opin Drug Saf. 2015;14(3):379–88.

    Article  CAS  PubMed  Google Scholar 

  53. Welch S et al. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Ann Oncol. 2010;21(6):1152–62.

    Article  CAS  PubMed  Google Scholar 

  54. Badgwell BD et al. Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol. 2008;19(3):577–82.

    Article  CAS  PubMed  Google Scholar 

  55. Scappaticci FA et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91(3):173–80.

    Article  CAS  PubMed  Google Scholar 

  56. Gruenberger B et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26(11):1830–5.

    Article  CAS  PubMed  Google Scholar 

  57. Cleary JM et al. Hepatic toxicities associated with the use of preoperative systemic therapy in patients with metastatic colorectal adenocarcinoma to the liver. Oncologist. 2009;14(11):1095–105.

    Article  PubMed  Google Scholar 

  58. Reddy SK et al. Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg. 2008;206(1):96–106.

    Article  PubMed  Google Scholar 

  59. Tamandl D et al. Liver resection remains a safe procedure after neoadjuvant chemotherapy including bevacizumab: a case-controlled study. Ann Surg. 2010;252(1):124–30.

    Article  PubMed  Google Scholar 

  60. Lubezky N et al. Perioperative complications after neoadjuvant chemotherapy with and without bevacizumab for colorectal liver metastases. J Gastrointest Surg. 2013;17(3):527–32.

    Article  PubMed  Google Scholar 

  61. Kesmodel SB et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26(32):5254–60.

    Article  PubMed  Google Scholar 

  62. Utsumi H et al. Bevacizumab and postoperative wound complications in patients with liver metastases of colorectal cancer. Anticancer Res. 2015;35(4):2255–61.

    CAS  PubMed  Google Scholar 

  63. Mahfud M et al. Impact of preoperative bevacizumab on complications after resection of colorectal liver metastases: case-matched control study. World J Surg. 2010;34(1):92–100.

    Article  PubMed  Google Scholar 

  64. Aussilhou B et al. Preoperative liver hypertrophy induced by portal flow occlusion before major hepatic resection for colorectal metastases can be impaired by bevacizumab. Ann Surg Oncol. 2009;16(6):1553–9.

    Article  PubMed  Google Scholar 

  65. Millet G et al. Volumetric analysis of remnant liver regeneration after major hepatectomy in bevacizumab-treated patients: a case-matched study in 82 patients. Ann Surg. 2012;256(5):755–61. discussion 761-2.

    Article  PubMed  Google Scholar 

  66. Chun YS et al. Management of chemotherapy-associated hepatotoxicity in colorectal liver metastases. Lancet Oncol. 2009;10(3):278–86.

    Article  CAS  PubMed  Google Scholar 

  67. Wicherts DA et al. Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases. Br J Surg. 2011;98(3):399–407.

    Article  CAS  PubMed  Google Scholar 

  68. Klinger M et al. Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol. 2009;35(5):515–20.

    Article  CAS  PubMed  Google Scholar 

  69. Robinson SM et al. Chemotherapy-associated liver injury in patients with colorectal liver metastases: a systematic review and meta-analysis. Ann Surg Oncol. 2012;19(13):4287–99.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Chun YS et al. Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA. 2009;302(21):2338–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shindoh J et al. Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol. 2012;30(36):4566–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Allegra CJ et al. Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial. J Clin Oncol. 2013;31(3):359–64.

    Article  CAS  PubMed  Google Scholar 

  73. de Gramont A et al. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012;13(12):1225–33.

    Article  PubMed  Google Scholar 

  74. Kerr DJ, Young AM. Targeted therapies: bevacizumab--has it reached its final resting place? Nat Rev Clin Oncol. 2011;8(4):195–6.

    Article  CAS  PubMed  Google Scholar 

  75. Snoeren N et al. A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment. BMC Cancer. 2010;10:545.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Rong Z et al. Impact of peri-operative bevacizumab on survival in patients with resected colorectal liver metastases: an analysis of the LiverMetSurvey. HPB (Oxford). 2014;16(4):342–9.

    Article  Google Scholar 

  77. Michael A, Relph K, Pandha H. Emergence of potential biomarkers of response to anti-angiogenic anti-tumour agents. Int J Cancer. 2010;127(6):1251–8.

    Article  CAS  PubMed  Google Scholar 

  78. Volz NB et al. Genes involved in pericyte-driven tumor maturation predict treatment benefit of first-line FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer. Pharmacogenomics J. 2015;15(1):69–76.

    Article  CAS  PubMed  Google Scholar 

  79. Sunakawa Y et al. Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials. Ann Oncol. 2015;26(12):2450–6.

    CAS  PubMed  Google Scholar 

  80. De Bruyne S et al. Value of DCE-MRI and FDG-PET/CT in the prediction of response to preoperative chemotherapy with bevacizumab for colorectal liver metastases. Br J Cancer. 2012;106(12):1926–33.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Lastoria S et al. Early PET/CT scan is more effective than RECIST in predicting outcome of patients with liver metastases from colorectal cancer treated with preoperative chemotherapy plus bevacizumab. J Nucl Med. 2013;54(12):2062–9.

    Article  CAS  PubMed  Google Scholar 

  82. Mir O et al. An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity. Oncologist. 2011;16(9):1325–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Petrelli F et al. Prognostic factors for survival with bevacizumab-based therapy in colorectal cancer patients: a systematic review and pooled analysis of 11,585 patients. Med Oncol. 2015;32(2):456.

    Article  PubMed  Google Scholar 

  84. Allard MA et al. Comparison of complete pathologic response and hepatic injuries between hepatic arterial infusion and systemic administration of oxaliplatin in patients with colorectal liver metastases. Ann Surg Oncol. 2015;22(6):1925–32.

    Article  PubMed  Google Scholar 

  85. Auer RC et al. Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy. Cancer. 2010;116(6):1502–9.

    Article  PubMed  Google Scholar 

  86. Cercek A et al. Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab. Ann Surg Oncol. 2014;21(2):479–86.

    Article  PubMed  Google Scholar 

  87. Kemeny NE et al. Randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer. J Clin Oncol. 2011;29(7):884–9.

    Article  CAS  PubMed  Google Scholar 

  88. Tsimberidou AM et al. A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer. 2010;116(17):4086–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Tsimberidou AM et al. Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver. Cancer Chemother Pharmacol. 2013;71(2):389–97.

    Article  CAS  PubMed  Google Scholar 

  90. Said R et al. Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver. Invest New Drugs. 2015;33(4):911–20.

    Article  CAS  PubMed  Google Scholar 

  91. Tsimberidou AM et al. A phase I study of hepatic arterial infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases. Cancer Chemother Pharmacol. 2013;71(4):955–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Van Cutsem E et al. 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. 2012;30(28):3499–506.

    Article  PubMed  Google Scholar 

  93. Tabernero J et al. 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. 2014;50(2):320–31.

    Article  CAS  PubMed  Google Scholar 

  94. Allegra CJ, et al. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015. J Clin Oncol. 2016;34(2):179–85. doi:10.1200/JCO.2015.63.9674.

  95. Adam R et al. Hepatic resection after rescue cetuximab treatment for colorectal liver metastases previously refractory to conventional systemic therapy. J Clin Oncol. 2007;25(29):4593–602.

    Article  CAS  PubMed  Google Scholar 

  96. Levi F et al. Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical resectability. Cancer Chemother Pharmacol. 2011;67(2):339–48.

    Article  CAS  PubMed  Google Scholar 

  97. Folprecht G et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11(1):38–47. Randomized trial with targeted therapy and onco-surgical main endpoint.

    Article  CAS  PubMed  Google Scholar 

  98. Primrose J et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol. 2014;15(6):601–11.

    Article  CAS  PubMed  Google Scholar 

  99. Tol J et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360(6):563–72.

    Article  CAS  PubMed  Google Scholar 

  100. Heinemann V et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75.

    Article  CAS  PubMed  Google Scholar 

  101. Schwartzberg LS et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240–7.

    Article  CAS  PubMed  Google Scholar 

  102. Feng QY et al. Anti-EGFR and anti-VEGF agents: important targeted therapies of colorectal liver metastases. World J Gastroenterol. 2014;20(15):4263–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Stintzing S, et al. LBA11 independent radiological evaluation of objective response, early tumor shrinkage, and depth of response in fire-3 (AIO KRK-0306) in the final ras evaluable population. Ann Oncol. 2014;25(suppl 4).

  104. Elez E, Argiles G, Tabernero J. First-line treatment of metastatic colorectal cancer: interpreting FIRE-3, PEAK, and CALGB/SWOG 80405. Curr Treat Options Oncol. 2015;16(11):52.

    Article  PubMed  Google Scholar 

  105. Vera R, et al. Current controversies in the management of metastatic colorectal cancer. Cancer Chemother Pharmacol. 2015;76(4):659–77. Overview of the landscape of medical treatment of metastatic colorectal cancer.

Download references

Author information

Authors and Affiliations

  1. Cancer Chronotherapy Unit, Cancer Research Centre, Warwick Medical School, University of Warwick, Coventry, Warwickshire, UK

    Pasquale F. Innominato

  2. Department of Oncology, Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Birmingham, UK

    Pasquale F. Innominato

  3. The Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Université Paris-Sud; INSERM U935, Villejuif, France

    René Adam

Authors
  1. Pasquale F. Innominato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. René Adam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to René Adam.

Ethics declarations

Conflict of Interest

Pasquale F. Innominato and René Adam declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Colorectal Cancer Hepatic Metastases

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Innominato, P.F., Adam, R. Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit. Curr Colorectal Cancer Rep 12, 208–216 (2016). https://doi.org/10.1007/s11888-016-0326-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-016-0326-5

Keywords

Search

Navigation