Skip to main content

Advertisement

SpringerLink
Log in

Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

We sought to find blood-based biomarkers that can be used to predict efficacy in advanced non-small cell lung cancer patients treated with bevacizumab plus chemotherapy. Blood was collected before treatment and after 6 weeks of therapy from patients who were participating in a phase 4 trial. Plasma vascular endothelial growth factor (VEGF) levels were evaluated by ELISA. A total of eight single nucleotide polymorphisms in four candidate genes were analyzed by PCR and sequencing. A total of 45 patients enrolled in a clinical trial at Guangdong General Hospital between August 2007 and March 2008 were used as subjects. The median survival times of OS was 25.6 and 13.4 months in the low and high groups, respectively, when the median posttreatment plasma VEGF level (46.63 pg/ml) was used as the cut-off point (P = 0.0284). Patients carrying the AA genotype at the −6C > A polymorphism in laminin 5 (LN5) were more likely to exhibit reduced hemoglobin compared with patients carrying the CA/CC genotype (OR = 8.364, χ2 = 5.34, P = 0.021). Similar associations were found at the −89A > G and −260C > A polymorphisms in LN5. Patients with the CC genotype at the −6C > A polymorphism in LN5 had an increased risk of neutropenia than those with the CA/AA genotype (OR = 4.444, χ2 = 5.116, P = 0.030). Our results show improved survival in patients with lower posttreatment plasma VEGF levels treated with bevacizumab plus chemotherapy; thus, the posttreatment plasma VEGF level may be a promising biomarker to predict clinical benefit early in the course of therapy. Polymorphisms in LN5 were associated with a reduced level of hemoglobin and neutropenia.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wheatley-Price P, Shepherd FA. Targeting angiogenesis in the treatment of lung cancer. J Thorac Oncol. 2008;3:1173–84.

    Article  PubMed  Google Scholar 

  2. Sandler A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med. 2006;355:2542–50.

    Article  PubMed  CAS  Google Scholar 

  3. Reck M, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010;21:1804–9.

    Article  PubMed  CAS  Google Scholar 

  4. Amir E, et al. Antivascular agents for non-small cell lung cancer: current status and future directions. Expert Opin Investig Drugs. 2009;18:1667–86.

    Article  PubMed  CAS  Google Scholar 

  5. Crinò L, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol. 2010;11:733–40.

    Article  PubMed  Google Scholar 

  6. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.

    Article  PubMed  CAS  Google Scholar 

  7. Willett CG, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–7.

    Article  PubMed  CAS  Google Scholar 

  8. Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev. 2005;15:102–11.

    Article  PubMed  CAS  Google Scholar 

  9. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62.

    Article  PubMed  CAS  Google Scholar 

  10. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med. 2001;7:987–9.

    Article  PubMed  CAS  Google Scholar 

  11. Saijo N, Kenmotsu H. Recent development of molecular-targeted drugs in lung cancer. Intern Med. 2010;49:1923–34.

    Article  PubMed  Google Scholar 

  12. Inai T, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004;165:35–52.

    Article  PubMed  CAS  Google Scholar 

  13. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–91.

    Article  PubMed  CAS  Google Scholar 

  14. Schneider BP, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26:4672–8.

    Article  PubMed  CAS  Google Scholar 

  15. An SJ, et al. The -271 G > A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer. BMC Cancer. 2009;9:144.

    Article  PubMed  Google Scholar 

  16. Huang YS, An SJ, Chen ZH, Wu YL. Three cases of severe hepatic impairment caused by erlotinib. Br J Clin Pharmacol. 2009;68:464–7.

    Article  PubMed  Google Scholar 

  17. Vroling L, et al. CD133 + circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients. Br J Cancer. 2010;102:268–75.

    Article  PubMed  CAS  Google Scholar 

  18. Wagstaff AJ, Keam SJ, McCormack PL. Bevacizumab plus platinum-based chemotherapy: in advanced non-small cell lung cancer. BioDrugs. 2009;23:187–96.

    Article  PubMed  CAS  Google Scholar 

  19. Sandler A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med. 2006;355:2542–50.

    Article  PubMed  CAS  Google Scholar 

  20. Nikolinakos PG, et al. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res. 2010;70:2171–9.

    Article  PubMed  CAS  Google Scholar 

  21. Hanrahan EO, et al. Distinct patterns of cytokine and angiogenic factor modulation and markers of benefit for vandetanib and/or chemotherapy in patients with non-small cell lung cancer. J Clin Oncol. 2010;28:193–201.

    Article  PubMed  CAS  Google Scholar 

  22. Miyazaki K. Laminin-5 (laminin-332): unique biological activity and role in tumor growth and invasion. Cancer Sci. 2006;97:91–8.

    Article  PubMed  CAS  Google Scholar 

  23. Fukai Y, et al. Correlation between laminin-5 gamma2 chain and epidermal growth factor receptor expression in esophageal squamous cell carcinomas. Oncology. 2005;69:71–80.

    Article  PubMed  CAS  Google Scholar 

  24. Giannelli G, et al. ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells. Biochem Pharmacol. 2006;71:479–85.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank Drs. Hong-Yan Tang, Hong-Sui Wu, and Shi-Liang Chen for their assistance with sample collection. This work was supported by grants from the National Natural Science Foundation of China (No. 30772531), Guangdong Provincial Medical Science and Technology Research Foundation (B2006001), and China Postdoctoral Science Foundation (20060400212).

Author information

Authors and Affiliations

  1. Medical Research Center of Guangdong General Hospital, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, Peoples Republic of China

    She-Juan An, Zhi-Hong Chen, Jian Su, Jian-Guang Chen, Hong-Hong Yan, Qiu-Xiong Lin, Xu-Chao Zhang & Yi-Long Wu

  2. Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, Peoples Republic of China

    Yi-Sheng Huang, Yan Yang, Jin-Ji Yang, Xue-Ning Yang, Qing Zhou & Yi-Long Wu

Authors
  1. She-Juan An
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi-Sheng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-Hong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jian Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian-Guang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong-Hong Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qiu-Xiong Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jin-Ji Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xue-Ning Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xu-Chao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yi-Long Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi-Long Wu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 250 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

An, SJ., Huang, YS., Chen, ZH. et al. Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy. Med Oncol 29, 627–632 (2012). https://doi.org/10.1007/s12032-011-9924-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-9924-x

Keywords

Search

Navigation