Skip to main content

Advertisement

Log in

Cetuximab: a standard approach to the first-line treatment of recurrent and/or metastatic and locally advanced squamous cell carcinoma of the head and neck

  • Review
  • Published:
Oncology Reviews

Abstract

The burden of squamous cell carcinoma of the head and neck (SCCHN) on healthcare systems is expected to rise in line with projected increases in population sizes in general, and the relative proportion of elderly individuals in particular, underlining the need for effective, well tolerated treatment strategies. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab, is the only EGFR-targeted agent currently approved for use in the treatment of SCCHN. Adding cetuximab to standard first-line platinum-based chemotherapy in the treatment of recurrent and/or metastatic SCCHN significantly improved overall survival (hazard ratio [HR] 0.80; P = 0.04), progression-free survival (HR 0.54; P < 0.001) and response rates (odds ratio 2.33; P < 0.001), compared to platinum-based chemotherapy alone. This was the first time in 30 years that a significant increase in overall survival had been achieved over platinum-based therapy alone and established cetuximab plus platinum-based chemotherapy as the new standard first-line treatment approach for recurrent and/or metastatic disease. In locally advanced SCCHN, cetuximab plus radiotherapy significantly improved locoregional control (HR 0.68, P = 0.005) and overall survival (HR 0.74; P = 0.03) compared to radiotherapy alone. In both recurrent and/or metastatic disease and locally advanced disease, adding cetuximab to standard therapy was generally well tolerated and did not affect patients’ quality of life. The clinical benefits seen with the addition of cetuximab to standard chemotherapy or radiotherapy make it one of the most significant advances made in SCCHN treatment in recent years.

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

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Ferlay J, Autier P, Boniol M et al (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592

    Article  CAS  PubMed  Google Scholar 

  3. Smith BD, Smith GL, Hurria A et al (2009) Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol 27:2758–2765

    Article  PubMed  Google Scholar 

  4. Nicholson RI, Gee JM, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37(Suppl 4):S9–S15

    Article  CAS  PubMed  Google Scholar 

  5. Christensen ME, Therkildsen MH, Hansen BL et al (1992) Epidermal growth factor receptor expression on oral mucosa dysplastic epithelia and squamous cell carcinomas. Eur Arch Otorhinolaryngol 249:243–247

    Article  CAS  PubMed  Google Scholar 

  6. Grandis JR, Melhem MF, Barnes EL, Tweardy DJ (1996) Quantitative immunohistochemical analysis of transforming growth factor-alpha and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck. Cancer 78:1284–1292

    Article  CAS  Google Scholar 

  7. Herbst RS, Shin DM (2002) Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer 94:1593–1611

    Article  CAS  PubMed  Google Scholar 

  8. Licitra L, Felip E (2009) Squamous cell carcinoma of the head and neck: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 20(Suppl 4):121–122

    PubMed  Google Scholar 

  9. Cohen EE, Lingen MW, Vokes EE (2004) The expanding role of systemic therapy in head and neck cancer. J Clin Oncol 22:1743–1752

    Article  PubMed  Google Scholar 

  10. Forastiere AA, Metch B, Schuller DE et al (1992) Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol 10:1245–1251

    CAS  PubMed  Google Scholar 

  11. Lokich J, Anderson N (1998) Carboplatin versus cisplatin in solid tumors: an analysis of the literature. Ann Oncol 9:13–21

    Article  CAS  PubMed  Google Scholar 

  12. Benasso M, Ponzanelli A, Merlano M et al (2006) Paclitaxel, cisplatin and 5-fluorouracil in recurrent squamous cell carcinoma of the head and neck: a phase II trial from an Italian cooperative group. Acta Oncol 45:168–174

    Article  CAS  PubMed  Google Scholar 

  13. Worden FP, Moon J, Samlowski W et al (2006) A phase II evaluation of a 3-hour infusion of paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: Southwest Oncology Group study 0007. Cancer 107:319–327

    Article  CAS  PubMed  Google Scholar 

  14. Burtness B, Goldwasser MA, Flood W 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 23:8646–8654

    Article  PubMed  Google Scholar 

  15. Bourhis J, Rivera F, Mesia R et al (2006) Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 24:2866–2872

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Jacobs C, Lyman G, Velez-Garcia E et al (1992) A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10:257–263

    CAS  PubMed  Google Scholar 

  18. Gibson MK, Li Y, Murphy B et al (2005) Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol 23:3562–3567

    Article  CAS  PubMed  Google Scholar 

  19. Hitt R, Irigoyen A, Nuñez J et al (2007) Phase II study of combination cetuximab and weekly paclitaxel in patients with metastatic/recurrent squamous cell carcinoma of head and neck (SCCHN): Spanish Head and Neck Cancer Group (TTCC). J Clin Oncol 25(18S):Abstract 6012. Virtual presentation http://www.asco.org

  20. Baselga J, Trigo JM, Bourhis J et al (2005) Phase ll multicenter study of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol 23:5568–5577

    Google Scholar 

  21. Buentzel J, de Vries A, Micke O (2007) Experience with cetuximab plus paclitaxel/carboplatinum in primary platinum-resistant recurrent head and neck cancer. J Clin Oncol 25(18S):Abstract 6077 (updated information presented at meeting)

  22. Herbst RS, Arquette M, Shin DM et al (2005) Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 23:5578–5587

    Article  CAS  PubMed  Google Scholar 

  23. Knoedler MK, Gauler T, Matzdorff A et al (2009) Multicenter phase II study of cetuximab plus docetaxel in 84 patients with recurrent or metastatic, platinum-pretreated SCCHN. J Clin Oncol 27(15S):Abstract 6048

  24. Vermorken JB, Trigo J, Hitt R et al (2007) Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25:2171–2177

    Google Scholar 

  25. Adelstein DJ, Li Y, Adams GL et al (2003) An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 21:92–98

    Article  PubMed  Google Scholar 

  26. Pignon JP, le Maitre A, Bourhis J (2007) Meta-Analyses of Chemotherapy in Head and Neck Cancer (MACH-NC): an update. Int J Radiat Oncol Biol Phys 69:S112–S114

    PubMed  Google Scholar 

  27. Wendt TG, Grabenbauer GG, Rodel CM et al (1998) Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 16:1318–1324

    CAS  PubMed  Google Scholar 

  28. Machtay M, Moughan J, Trotti A et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26:3582–3589

    Article  CAS  PubMed  Google Scholar 

  29. Eisbruch A (2007) Commentary: induction chemotherapy for head and neck cancer: hypothesis-based rather than evidence-based medicine. Oncologist 12:975–977

    Article  PubMed  Google Scholar 

  30. Posner MR, Hershock DM, Blajman CR et al (2007) Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 357:1705–1715

    Article  CAS  PubMed  Google Scholar 

  31. Vermorken JB, Remenar E, van Herpen C et al (2007) Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 357:1695–1704

    Article  CAS  PubMed  Google Scholar 

  32. (1991) Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324:1685–1690

  33. Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  CAS  PubMed  Google Scholar 

  34. Bonner JA, Harari PM, Giralt J et al (2008) Prolongation of survival with the addition of cetuximab to radiation in patients with locoregionally advanced head and neck cancer (SCCHN): five-year results from a randomized trial. ASTRO, Boston, MA, USA, 19–25 September

  35. Caudell JJ, Sawrie SM, Spencer SA et al (2008) Locoregionally advanced head and neck cancer treated with primary radiotherapy: a comparison of the addition of cetuximab or chemotherapy and the impact of protocol treatment. Int J Radiat Oncol Biol Phys 71:678–681

    Google Scholar 

  36. Giro C, Berger B, Bolke E et al (2009) High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes. Radiother Oncol 90:166–171

    Article  CAS  PubMed  Google Scholar 

  37. Pryor DI, Porceddu SV, Burmeister BH et al (2009) Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol 90:172–176

    Article  CAS  PubMed  Google Scholar 

  38. Bernier J, Bonner J, Vermorken JB et al (2007) Consensus guidelines for the management of radiation dermatitis and co-existing acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol 19:142–149

    Article  PubMed  Google Scholar 

  39. Lefebvre JL, Pointreau Y, Rolland F et al. (2009) Sequential chemoradiotherapy (SCRT) for larynx preservation (LP): preliminary results of the randomized phase II TREMPLIN study. J Clin Oncol 27(15S):Abstract 6010

  40. Zhang N, Erjala K, Kulmala J et al (2009) Concurrent cetuximab, cisplatin, and radiation for squamous cell carcinoma of the head and neck in vitro. Radiother Oncol 92:388–392

    Article  CAS  PubMed  Google Scholar 

  41. Argiris AE, Gibson MK, Heron DE et al (2008) Phase II trial of neoadjuvant docetaxel (T), cisplatin (P), and cetuximab (E) followed by concurrent radiation (X), P, and E in locally advanced head and neck cancer (HNC). J Clin Oncol 26:Abstract 6002. Virtual presentation http://www.asco.org

  42. Langer CJ, Lee JW, Patel AU et al (2008) Preliminary analysis of ECOG 3303: Concurrent radiation (RT), cisplatin (DDP) and cetuximab (C) in unresectable, locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol 26:Abstract 6006. Virtual presentation http://www.asco.org

  43. Tishler RB, Posner MR, Wirth LJ et al (2008) Cetuximab added to docetaxel, cisplatin, 5-fluorouracil induction chemotherapy (C-TPF) in patients with newly diagnosed locally advanced head and neck cancer: A phase I study. J Clin Oncol 26:Abstract 6001

  44. Vermorken JB, Mesia R, Remenar E et al (2008) Predictors of efficacy in the EXTREME study: cetuximab plus platinum-based therapy first-line in patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol 19(Suppl 8):Abstract 687O (updated information presented at the meeting)

  45. Anderson JA, Irish JC, Ngan BY (1992) Prevalence of RAS oncogene mutation in head and neck carcinomas. J Otolaryngol 21:321–326

    CAS  PubMed  Google Scholar 

  46. Rathcke IO, Gottschlich S, Gorogh T et al (1996) Incidence of point mutations in Ki-ras codon 12 and 13 in squamous epithelial carcinomas of the head-neck region. Laryngorhinootologie 75:465–470

    Article  CAS  PubMed  Google Scholar 

  47. Italiano A, Follana P, Caroli FX et al (2008) Cetuximab shows activity in colorectal cancer patients with tumors for which FISH analysis does not detect an increase in EGFR gene copy number. Ann Surg Oncol 15:649–654

    Article  PubMed  Google Scholar 

  48. Licitra L, Rolland F, Bokemeyer C et al (2009) Biomarker potential of EGFR gene copy number by FISH in the phase III EXTREME study: platinum-based CT + cetuximab in 1st-line R/M SCCHN. J Clin Oncol 27(15S):Abstract 6005

  49. Elting LS, Keefe DM, Sonis ST et al (2008) Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer 113:2704–2713

    Article  PubMed  Google Scholar 

  50. Jellema AP, Slotman BJ, Doornaert P et al (2007) Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer. Int J Radiat Oncol Biol Phys 69:751–760

    PubMed  Google Scholar 

  51. Rogers LQ, Rao K, Malone J et al (2009) Factors associated with quality of life in outpatients with head and neck cancer 6 months after diagnosis. Head Neck 31:1207–1214

    Article  PubMed  Google Scholar 

  52. El-Deiry MW, Futran ND, McDowell JA et al (2009) Influences and predictors of long-term quality of life in head and neck cancer survivors. Arch Otolaryngol Head Neck Surg 135:380–384

    Article  PubMed  Google Scholar 

  53. Rivera Herrero F, Hitt R, Kawecki A et al (2008) Cetuximab plus platinum-based therapy first-line in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: a quality of life (QOL) analysis of the EXTREME trial. Ann Oncol 19(Suppl 8):Abstract 693PD (updated information presented at meeting)

  54. Curran D, Giralt J, Harari PM et al (2007) Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25:2191–2197

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Jacques Bernier received editorial support for the production of this manuscript which was funded by Merck KGaA.

Conflict of interest statement

No conflicts of interest are present for this paper.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jacques Bernier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernier, J. Cetuximab: a standard approach to the first-line treatment of recurrent and/or metastatic and locally advanced squamous cell carcinoma of the head and neck. Oncol Rev 3, 247–256 (2009). https://doi.org/10.1007/s12156-009-0026-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12156-009-0026-3

Keywords

Navigation