Skip to main content

Advertisement

Log in

Role of bevacizumab in neoadjuvant chemotherapy and its influence on microvessel density in rectal cancer

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

The role of bevacizumab (Bev) in neoadjuvant chemotherapy (NAC) without radiotherapy for rectal cancer has not been fully discussed. The purpose of this study is to assess the clinicopathological benefit of Bev in NAC for rectal cancer and to investigate its influence on microvessel status in cancerous tissue.

Methods

Data on 47 patients with rectal cancer, who received NAC with or without Bev between August 2008 and November 2012, were analyzed retrospectively. The objective response was evaluated using the maximum tumor diameter. Tumor regression grade 3/4 was classified as a pathological response.

Results

Thirty-one patients (66 %) received NAC that included Bev and the other 16 patients were treated without Bev. The objective response rate was significantly higher in the Bev group than in the non-Bev group (64.5 vs. 25.0 %, p = 0.015). The rate of pathological response was much higher in the Bev group (41.9 %) than in the non-Bev group (12.5 %), but did not reach significant difference (p = 0.052). Microvessel density (MVD) in the resected cancerous tissue was significantly lower in the Bev group than in the non-Bev group.

Conclusions

We have confirmed that objective and pathological responses were better in patients treated with NAC that included Bev than in those who received NAC without Bev. Additionally, MVD in tumor tissues was inhibited in the patients treated with Bev. To investigate the impact of Bev in NAC on long-term survival, further follow-up is required.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934

    CAS  PubMed  Google Scholar 

  2. Folkman J (1995) Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 333:1757–1763

    Article  CAS  PubMed  Google Scholar 

  3. Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674

    Article  CAS  PubMed  Google Scholar 

  4. Longatto Filho A, Lopes JM, Schmitt FC (2010) Angiogenesis and breast cancer. J Oncol. doi:10.1155/2010/576384

    PubMed Central  PubMed  Google Scholar 

  5. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  CAS  PubMed  Google Scholar 

  6. Miller KD, Chap LI, Holmes FA et al (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23:792–799

    Article  CAS  PubMed  Google Scholar 

  7. Escudier B, Pluzanska A, Koralewski P et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111

    Article  PubMed  Google Scholar 

  8. 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

    Article  CAS  PubMed  Google Scholar 

  9. Ferrara N, Hillan KJ, Novotny W (2005) Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333:328–335

    Article  CAS  PubMed  Google Scholar 

  10. 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

    Article  CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. Uehara K, Ishiguro S, Sakamoto E et al (2011) Phase II trial of neoadjuvant chemotherapy with XELOX plus bevacizumab for locally advanced rectal cancer. Jpn J Clin Oncol 41:1041–1044. doi:10.1093/jjco/hyr084

    Article  PubMed  Google Scholar 

  13. Uehara K, Hiramatsu K, Maeda A et al (2013) Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol 43:964–971. doi:10.1093/jjco/hyt115

    Article  PubMed  Google Scholar 

  14. Schrag D, Weiser MR, Goodman KA et al (2014) Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol 32:513–518. doi:10.1200/JCO.2013.51.7904

    Article  CAS  PubMed  Google Scholar 

  15. Nasti G, Piccirillo MC, Izzo F et al (2013) Neoadjuvant FOLFIRI + bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial. Br J Cancer 108:1566–1570. doi:10.1038/bjc

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Meert AP, Paesmans M, Martin B et al (2002) The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 87:694–701

    Article  PubMed Central  PubMed  Google Scholar 

  17. Murri AM, Hilmy M, Bell J et al (2008) The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer. Br J Cancer 99:1013–1019. doi:10.1038/sj.bjc.6604667

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. de Oliveira MV, Pereira Gomes EP, Pereira CS et al (2013) Prognostic value of microvessel density and p53 expression on the locoregional metastasis and survival of the patients with head and neck squamous cell carcinoma. Appl Immunohistochem Mol Morphol 21:444–451. doi:10.1097/PAI.0b013e3182773125

    Article  PubMed  Google Scholar 

  19. Uehara M, Sano K, Ikeda H et al (2004) Expression of vascular endothelial growth factor and prognosis of oral squamous cell carcinoma. Oral Oncol 40:321–325

    Article  CAS  PubMed  Google Scholar 

  20. Zhao YY, Xue C, Jiang W et al (2012) Predictive value of intratumoral microvascular density in patients with advanced non-small cell lung cancer receiving chemotherapy plus bevacizumab. J Thorac Oncol 7:71–75. doi:10.1097/JTO.0b013e31823085f4

    Article  PubMed  Google Scholar 

  21. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Yanagisawa M, Fujimoto-Ouchi K, Yorozu K et al (2009) Antitumor activity of bevacizumab in combination with capecitabine and oxaliplatin in human colorectal cancer xenograft models. Oncol Rep 22:241–247

    CAS  PubMed  Google Scholar 

  23. Patel UB, Brown G, Rutten H et al (2012) Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol 19:2842–2852. doi:10.1245/s10434-012-2309-3

    Article  PubMed  Google Scholar 

  24. Watanabe T, Itabashi M, Shimada Y et al (2012) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol 17:1–29. doi:10.1007/s10147-011-0315-2

    Article  PubMed  Google Scholar 

  25. Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23

    Article  CAS  PubMed  Google Scholar 

  26. Cunningham D, Lang I, Marcuello E et al (2013) 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 

  27. 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 

  28. de Gramont A, Van Cutsem E, Schmoll HJ et al (2012) Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 13:1225–1233. doi:10.1016/S1470-2045(12)70509-0

    Article  PubMed  Google Scholar 

  29. Allegra CJ, Yothers G, O’Connell MJ et al (2011) Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 29:11–16. doi:10.1200/JCO.2010.30.0855

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Yeo SG, Kim DY, Kim TH et al (2010) Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01). Ann Surg 252:998–1004. doi:10.1097/SLA.0b013e3181f3f1b1

    Article  PubMed  Google Scholar 

  31. Maas M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844. doi:10.1016/S1470-2045(10)70172-8

    Article  PubMed  Google Scholar 

  32. Lee YC, Hsieh CC, Chuang JP (2013) Prognostic significance of partial tumor regression after preoperative chemoradiotherapy for rectal cancer: a meta-analysis. Dis Colon Rectum 56:1093–1101. doi:10.1097/DCR.0b013e318298e36b

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Keisuke Uehara.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arimoto, A., Uehara, K., Tsuzuki, T. et al. Role of bevacizumab in neoadjuvant chemotherapy and its influence on microvessel density in rectal cancer. Int J Clin Oncol 20, 935–942 (2015). https://doi.org/10.1007/s10147-015-0818-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-015-0818-3

Keywords

Navigation