Skip to main content

Advertisement

Log in

Anti-epidermal growth factor receptor therapy for advanced head and neck squamous cell carcinoma: a meta-analysis

European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

To assess the efficacy and safety of anti-epidermal growth factor receptor (EGFR) therapy versus non-anti-EGFR therapy for advanced head and neck squamous cell carcinoma (HNSCC).

Methods

The Cochrane Central Register of Controlled Trials, Medline, and Embase databases were searched for relevant reports. Quantitative analysis was carried out to evaluate the overall response rate (ORR), overall survival (OS), progression free survival (PFS), and grade 3–4 adverse effects.

Results

Ten reports involving 2,396 patients were included. Primary meta-analysis indicated that anti-EGFR therapy could improve ORR [relative risk (RR) 1.36, 95% confidence interval (CI) 1.12–1.67] and PFS [hazard ratio (HR) 0.63, 95% CI 0.55–0.71), but failed to improve OS (HR 0.88, 95% CI 0.74–1.03). In subgroup analyses, we found that monoclonal antibodies (Mabs) could improve ORR, OS, and PFS for both locoregionally advanced (LA) (ORR: 1.21, 1.08–1.37; OS: 0.72, 0.59–0.89; PFS: 0.66, 0.53–0.83) and recurrent/metastatic (RM) HNSCC (ORR: 1.88, 1.40–2.54; OS: 0.79, 0.67–0.94; PFS: 0.61, 0.52–0.71), while tyrosine kinase inhibitors (TKIs) did not improve any of these in patients with either LA (ORR: 1.09, 0.91–1.32; OS: 0.7, 0.31–1.63; PFS: 0.71, 0.34–1.52) or RM (ORR: 1.65, 0.84–3.24; OS: 1.13, 0.97–1.31; PFS: not available) HNSCC. Analysis of adverse effects demonstrated that rash (RR 14.34, 95% CI 5.02–41.02), diarrhea (2.36, 1.15–4.87), and anorexia (2.49, 1.11–5.56) were significantly associated with anti-EGFR therapy.

Conclusions

Anti-EGFR Mabs are effective for both LA and RM HNSCC. In contrast, TKIs were unsuitable for treatment of advanced HNSCC. During anti-EGFR therapy, rash and some gastrointestinal reactions, such as diarrhea and anorexia, should be carefully monitored.

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.

Institutional subscriptions

Fig.1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Choong N, Vokes E (2008) Expanding role of the medical oncologist in the management of head and neck cancer. CA Cancer J Clin 58(1):32–53

    Article  PubMed  Google Scholar 

  2. American Cancer Society (2011) Cancer facts and figures 2011. ACS, Atlanta

  3. Lee J, Moon C (2011) Current status of experimental therapeutics for head and neck cancer. Exp Biol Med 236(4):375–389

    Article  CAS  Google Scholar 

  4. Papaspyrou G, Werner JA et al (2011) Pharmacotherapy for squamous-cell carcinoma of the head and neck. Expert Opin Pharmacother 12(3):397–409

    Article  PubMed  CAS  Google Scholar 

  5. Seiwert TY, Salama JK et al (2007) The chemoradiation paradigm in head and neck cancer. Nat Clin Pract Oncol 4(3):156–171

    Article  PubMed  CAS  Google Scholar 

  6. Goerner M, Seiwert TY et al (2010) Molecular targeted therapies in head and neck cancer—an updated of recent developments. Head Neck Oncol 2:8

    Article  PubMed  Google Scholar 

  7. Hynes NE, Lane HA (2005) Erbb receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354

    Article  PubMed  CAS  Google Scholar 

  8. Szabó B, Nelhubel GA et al (2011) Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. Oral Oncol 47(6):487–496

    Article  PubMed  Google Scholar 

  9. Ang KK, Berkey BA et al (2002) Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62(24):7350–7356

    PubMed  CAS  Google Scholar 

  10. Grandis R, Melhem MF et al (1998) Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst 90(11):824–832

    Article  Google Scholar 

  11. Gold KA, Lee HY et al (2009) Targeted therapies in squamous cell carcinoma of the head and neck. Cancer 115(5):922–35

    Article  PubMed  CAS  Google Scholar 

  12. Bonner JA, Harari PM (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354(6):567–78

    Article  PubMed  CAS  Google Scholar 

  13. Ramakrishnan MS, Eswaraiah A et al (2009) Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. Mabs 1(1):41–48

    Article  PubMed  Google Scholar 

  14. Chou J, Lin YC et al (2008) Nasopharyngeal carcinoma—review of the molecular mechanisms of tumorigenesis. Head Neck 30(7):946–963

    Article  PubMed  Google Scholar 

  15. Chan AT, Felip E et al. (2009) Nasopharyngeal cancer: EMSO clinical recommendations for diagnosis treatment and follow-up. Ann Oncol Suppl 4:123–125

    Google Scholar 

  16. Siersema PD (2008) Esophageal cancer. Gastroenterol Clin North Am 37(4):943–964

    Article  PubMed  Google Scholar 

  17. Williamson PR, Smith CT et al (2002) Aggregate data meta-analysis with time-to-event outcomes. Stat Med 21(22):3337–3351

    Article  PubMed  Google Scholar 

  18. Jadad AR, Moore RA et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12

    Article  PubMed  CAS  Google Scholar 

  19. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  20. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  PubMed  CAS  Google Scholar 

  21. Egger M, Davey Smith G (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  PubMed  CAS  Google Scholar 

  22. Del Campo JM, Sebastian P (2008) Results of a phase II randomised study in patients with locally advanced squamous cell carcinoma of the head and neck. Abstract #688O. 3rd ESMO Congress

  23. Rodríguez MO, Rivero TC et al (2010) Nimotuzumab plus radiotherapy for unresectable squamous cell carcinoma of the head and neck. Cancer Biol Ther 9(5):343–349

    Article  PubMed  Google Scholar 

  24. Harrington KJ, Berrier A et al. (2010) Phase II study of oral lapatinib, a dual-tyrosine kinase inhibitor, combined with chemoradiotherapy in patients with locally advanced, unresected squamous cell carcinoma of the head and neck. Abstract #5505. ASCO

  25. Burtness B, Goldwasser MA et al (2005) Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 23(34):8646–8654

    Article  PubMed  Google Scholar 

  26. Vermorken JB, Mesia R et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359(11):1116–1127

    Article  PubMed  CAS  Google Scholar 

  27. Stewart JS, Cohen EE et al (2009) Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 27(11):1864–1871

    Article  PubMed  CAS  Google Scholar 

  28. Argiris A, Ghebremichael M et al. (2009) A phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: a trial of Eastern Cooperative Oncology Group. ASCO

  29. Machiels JP, Subramanian S et al (2011) Zalutumumab plus best supportive care alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol 12(4):333–343

    Article  PubMed  CAS  Google Scholar 

  30. Pazdur R (2008) Endpoints for assessing drug activity in clinical trials. Oncologist Suppl 2:19–21

    Google Scholar 

  31. Feng FY, Lopez CA et al (2007) Effect of epidermal factor receptor inhibitor class in the treatment of head and neck cancer with concurrent radiochemotherapy in vivo. Clin Cancer Res 13(8):2512–2518

    Article  PubMed  CAS  Google Scholar 

  32. Vivanco I, Mellinghoff IK (2010) Epidermal growth factor receptor inhibitors in oncology. Curr Opin Oncol 22(6):573–578

    Article  PubMed  CAS  Google Scholar 

  33. Cohen MH, Williams GA et al (2004) United States Food and Drug Administration Drug Approval summary: gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 10(4):1212–1218

    Article  PubMed  CAS  Google Scholar 

  34. Golsteyn RM (2005) Gefitinib dose not increase survival in lung cancer patients. Drug Discov Today 10(6):381

    Article  PubMed  Google Scholar 

  35. Carlson JJ (2009) Erlotinib in non-small-cell lung cancer: a review of the clinical and economic evidence. Expert Rev Pharmacoecon Outcome Res 9(5):409–416

    Article  Google Scholar 

  36. Rothenberg ML, LaFleur B et al (2005) Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J Clin Oncol 23(36):9265–9274

    Article  PubMed  CAS  Google Scholar 

  37. Santoro A, Comandone A et al (2008) A phase II randomized multicenter trial of gefitinib plus FOLFIRI and FOLFIRI alone in patients with metastatic colorectal cancer. Ann Oncol 19(11):1888–1893

    Article  PubMed  CAS  Google Scholar 

  38. Viéitez JM, Valladares M et al (2011) A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143). Invest New Drugs 29(5):1038–1044

    Article  PubMed  Google Scholar 

  39. da Cunha Santos G, Shepherd FA et al (2011) EGFR mutations and lung cancer. Annu Rev Pathol 6:49–69

    Article  PubMed  Google Scholar 

  40. Oh BY, Lee RA et al (2011) Epidermal growth factor receptor mutations in colorectal cancer patients. J Korean Soc Coloproctol 27(3):127–132

    Article  PubMed  Google Scholar 

  41. Cooper JB, Cohen EE et al (2009) Mechanisms of resistance to EGFR inhibitors in head and neck cancer. Head Neck 31(8):1086–1094

    Article  PubMed  Google Scholar 

  42. Chen P, Wang L et al (2011) EGFR-targeted therapies combined with chemotherapy for treating advanced non-small-cell lung cancer: a meta-analysis. Eur J Clin Pharmacol 67(3):235–243

    Article  PubMed  CAS  Google Scholar 

  43. Dassonville O, Bozec A et al (2007) EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences. Crit Rev Oncol Hematol 62(1):53–61

    Article  PubMed  Google Scholar 

  44. Lacouture ME (2006) Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 6(10):803–812

    Article  PubMed  CAS  Google Scholar 

  45. Sipples R (2006) Common side effects of anti-EGFR therapy: acneform rash. Semin Oncol Nurs 1 (Suppl 1):28–34

    Google Scholar 

Download references

Acknowledgements

The study was supported by the grant from National Natural Science Foundation of China (No. 81172561).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Beibei Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, S., Chen, J., Jiang, H. et al. Anti-epidermal growth factor receptor therapy for advanced head and neck squamous cell carcinoma: a meta-analysis. Eur J Clin Pharmacol 68, 561–569 (2012). https://doi.org/10.1007/s00228-011-1194-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-011-1194-1

Keywords

Navigation