Skip to main content

Advertisement

SpringerLink
Log in

Strategies for Non-Resectable Head and Neck Cancer

  • Head and Neck Cancer (JB Vermorken, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion Statement

Treatment of unresectable, locally advanced head and neck cancer consists of many different options, all of them based on radiotherapy. The main variable is represented by chemotherapy, i.e., the way in which chemotherapy is combined with radiation. More recently, the combination of cetuximab and radiotherapy emerged as a new treatment opportunity and induction chemotherapy, with the combination of docetaxel, cisplatin, and 5-fluoruracil, gained a renewed interest. Concurrent chemoradiation is based on the most robust evidence and is regarded as the leading standard of care for unresectable locally advanced head and neck cancer. Unfortunately, chemoradiation is hampered by severe toxicity and patients must be selected carefully before treatment. The experience of the staff (medical oncologists, radiation oncologists, and nurses), and in particular its familiarity with toxicity management, as well the structural facilities, play an important role in the final outcome. When the patient is unfit for chemoradiation, or when experienced staff or adequate structures are unavailable, induction chemotherapy, cetuximab and radiotherapy, or radiotherapy alone are all evidence-based alternative options. The choice among them will be based on the clinical condition of the patient, the physician’s experience, and the patient’s preference. Whatever is the treatment of choice, it is important to involve a multidisciplinary staff in the management of these patients. Indeed, also unresectable patients may require supportive surgical interventions before or during treatment, or removal of residual disease after treatment.

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 and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Shibuya K, Mathers CD, Boschi-Pinto C, et al. Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000. BMC Cancer. 2002;2:37.

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  3. Yousem DM, Gad K, Tufano RP. Resectability issues with head and neck cancer. AJNR Am J Neuroradiol. 2006;27:2024–36.

    PubMed  CAS  Google Scholar 

  4. Fu KK, Pajak TF, Trotti A, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000;48:7–16.

    Article  PubMed  CAS  Google Scholar 

  5. Laskar SG, Agarwal JP, Srinivas C, Dinshaw KA. Radiotherapeutic management of locally advanced head and neck cancer. Expert Rev Anticancer Ther. 2006;6:405–17.

    Article  PubMed  Google Scholar 

  6. Bourhis J, Overgaard J, Audry H, et al. Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH) Collaborative Group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet. 2006;368:843–54.

    Article  PubMed  Google Scholar 

  7. Horiot JC, Le Fur R, N’Guyen T, et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol. 1992;25:231–41.

    Article  PubMed  CAS  Google Scholar 

  8. Overgaard J, Hansen HS, Specht L, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet. 2003;362:933–40.

    Article  PubMed  Google Scholar 

  9. Saunders MI, Rojas AM, Parmar MK, Dische S, CHART Trial Collaborators. Mature results of a randomized trial of accelerated hyperfractionated versus conventional radiotherapy in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010;77:3–8.

    Article  PubMed  Google Scholar 

  10. Corvò R, Benasso M, Sanguineti G, Lionetto R, Bacigalupo A, Margarino G, et al. Alternating chemoradiotherapy versus partly accelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck: results from a phase III randomized trial. Cancer. 2001;92:2856–67.

    Article  PubMed  Google Scholar 

  11. Rathod S, Gupta T, Ghosh-Laskar S, Murthy V, Budrukkar A, Prakash J. Agarwal Quality-of-life (QOL) outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT): Evidence from a prospective randomized study. Oral Oncol. 2013;49:634–42.

    Article  PubMed  Google Scholar 

  12. Ramaekers BLT, Pijls-Johannesma M, Joore MA, van den Ende P, Langendijk JA, Lambin P, et al. Systematic review and meta-analysis of radiotherapy in various head and neck cancers: comparing photons, carbon-ions and protons. Cancer Treatment Rev. 2011;37:185–201.

    Article  CAS  Google Scholar 

  13. Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355:949–55.

    PubMed  CAS  Google Scholar 

  14. Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group.Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92(1):4–14. A landmark meta-analysis of chemotherapy in locally advanced head and neck cancer.

    Article  PubMed  Google Scholar 

  15. Adelstein DJ, Li Y, Adams GL, et al. 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. 2003;21:92–8.

    Article  PubMed  Google Scholar 

  16. Budach W, Hehr T, Budach V, et al. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer. 2006;6:28.

    Article  PubMed  CAS  Google Scholar 

  17. Benasso M, Corvò R, Ponzanelli A, et al. Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck. Ann Oncol. 2004;15:646–52.

    Article  PubMed  CAS  Google Scholar 

  18. Garden AS, Harris J, Vokes EE, et al. Preliminary results of Radiation Oncology Group 97–03: a randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004;22:2856–64.

    Article  PubMed  CAS  Google Scholar 

  19. Rosen F, Haraf DJ, Kies MS, et al. Multicenter randomized phase II study of paclitaxel (1-hour infusion), fluoruracil, hydrossiurea and concomitant twice daily radiation with or without erythropoietin for advanced head and neck cancer. Clin Cancer Res. 2003;9:1689–97.

    PubMed  CAS  Google Scholar 

  20. Seiwert TY, Salama JK, Vokes EE. The chemoradiation paradigm in head and neck cancer. Nat Clin Pract Oncol. 2007;4:156–71.

    Article  PubMed  CAS  Google Scholar 

  21. Merlano MC, Monteverde M, Colantonio I, et al. Impact of age on acute toxicity induced by bio- or chemo-radiotherapy in patients with head and neck cancer. Oral Oncol. 2012;10:1051–7.

    Article  Google Scholar 

  22. Sibilia M, Kroismayr R, Lichtemberger BM, et al. The epidermal growth factor receptor: from development to tumorigenesis. Differentiation. 2007;75:770–87.

    Article  PubMed  CAS  Google Scholar 

  23. Ke LD, Adler-Storthz K, Clayman GL, et al. Differential expression of epidermal growth factor receptor in human head and neck cancers. Head and Neck. 1998;20:320–7.

    Article  PubMed  CAS  Google Scholar 

  24. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–78.

    Article  PubMed  CAS  Google Scholar 

  25. Bonner JA, Harari PM, Girault J, et al.: Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomized trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010,11:21–28. The only phase III trial showing an advantage from the combination of radiotherapy and an EGFR inhibitor.

    Article  PubMed  CAS  Google Scholar 

  26. Merlano M, Russi E, Benasso M, et al. Cisplatin based chemoradiation plus cetuximab in locally advanced head and neck cancer. Ann Oncol. 2011;22:712–7.

    Article  PubMed  CAS  Google Scholar 

  27. Pfister DG, Su YB, Kraus DH, et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. J Clin Oncol. 2006;24:1072–8.

    Article  PubMed  CAS  Google Scholar 

  28. Langer CJ, Lee JW, Patel UA, et al. 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. 2008;26(15S):6006.

    Google Scholar 

  29. Girault J, Fortin A, Mesia R, et al. A phase II, randomized trial (CONCERT-1) of chemoradiotherapy (CRT) with or without panitumumab (pmab) in patients (pts) with unresected, locally advanced squamous cell carcinoma of the head and neck (LASCCHN). J Clin Oncol. 2012;30(15S):5502.

    Google Scholar 

  30. Martins RG, Parvathanemi U, Bauman JE, et al. Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial. J Clin Oncol. 2013;31:1415–21.

    Article  PubMed  CAS  Google Scholar 

  31. Ang KK, Zhang Q, Rosenthal DI, et al. A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (HNC). J Clin Oncol. 2011;29(15S):5500.

    Google Scholar 

  32. Looney WB, Hpkins HA, Carter WH, et al. Solid tumor models for the assessment of different treatment modalities: XXIII. A new approach to the more effective utilization of radiotherapy alternated with chemotherapy. Int J Radiat Oncol Biol Phys. 1985;11:2105–17.

    Article  PubMed  CAS  Google Scholar 

  33. Merlano M, Vitale V, Rosso R, et al. Treatment of advanced squamous cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. N Engl J Med. 1992;327:1115–21.

    Article  PubMed  CAS  Google Scholar 

  34. South-East Co-operative Oncology Group. A randomized trial of combined multidrug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck. An interim report from the SECOG participants. Eur J Surg Oncol. 1986;12:289–95.

    Google Scholar 

  35. Merlano M, Corvo R, Margarino G, et al. Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer. 1991;67:915–21.

    Article  PubMed  CAS  Google Scholar 

  36. Lefebvre JL, Rolland F, Tesselaar M, et al.: Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009;101:142–152. The alternating regimen shows a lower acute toxicity compared with induction chemotherapy followed by radiation.

    Article  PubMed  CAS  Google Scholar 

  37. Posner MR. Paradigm shift in the treatment of head and neck cancer: the role of neoadjuvant chemotherapy. Oncologist. 2005;10(S3):11–9.

    Article  PubMed  CAS  Google Scholar 

  38. Paccagnella A, Orlando A, Marchiori C, et al. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: A study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst. 1994;86:265–72.

    Article  PubMed  CAS  Google Scholar 

  39. Zorat PL, Paccagnella A, Cavaniglia G, et al. Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up. J Natl Cancer Inst. 2004;96:1714–7.

    Article  PubMed  CAS  Google Scholar 

  40. Domenge C, Hill C, Lefebvre JL, et al. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Grup d’Etude des Tumeurs de la tete et du Cou (GETTEC). Br J Cancer. 2000;83:1594–8.

    Article  PubMed  CAS  Google Scholar 

  41. Vermorken JB, Remenar E, Van Harpen C, et al. Cisplatin, fluorouracil and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695–704.

    Article  PubMed  CAS  Google Scholar 

  42. Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357:1705–15.

    Article  PubMed  CAS  Google Scholar 

  43. Blanchard P, Bhouris J, Lacas B, et al. Taxane-cisplatin-fluorocil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013;31:2854–60.

    Article  PubMed  CAS  Google Scholar 

  44. Ma J, Liu Y, Yang X, et al. Induction chemotherapy in patients with resectable head and neck squamous cell carcinoma: a meta-analysis. World J Surg Oncol. 2013;11:67.

    Article  PubMed  Google Scholar 

  45. Haddad R, O’Neil A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomized phase 3 trial. Lancet Oncol. 2013;14:257–64.

    Article  PubMed  CAS  Google Scholar 

  46. Cohen EEW, Karrison T, Kocherginsky M, et al. DeCIDE: a phase III randomized trial of docetaxel (D), cisplatin (C), 5-fluoruracil (F)(TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 2012;30(15S):5500.

    Google Scholar 

  47. Lefebvre JL, Pointreau Y, Rolland F, et al.: Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the tremplin randomized phase II study. J Clin Oncol 2013,31:853–859. This study points out the toxicity of induction chemotherapy and either chemoradiation or bioradiation.

    Article  PubMed  CAS  Google Scholar 

  48. Driessen C, De Boer JP, Gelderblom H, et al. Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil (TPF) followed by cisplatin-containing concomitant chemoradiotherapy (CRT) in fit patients with locally advanced head and neck cancer (LAHNC): the CONDOR study – a study of the Dutch Head and Neck Society. J Clin Oncol. 2013;31(15S):6057.

    Google Scholar 

  49. Trotti A. Toxicity in head and neck cancer: a review of trends and issues. Int J Radiat Oncol Biol Phys. 2000;47:1–12.

    Article  PubMed  CAS  Google Scholar 

  50. Vokes EE, Kies MS, Haraf DJ, et al. Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer. J Clin Oncol. 2000;18:1652–61.

    PubMed  CAS  Google Scholar 

  51. Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91–11: a comparison of three non surgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013,31:845–852. Important study evaluating late toxicity and non-cancer-related death among three different organ-preservation approaches.

    Article  PubMed  CAS  Google Scholar 

  52. Ghadjar P, Simcock M, Studer G, et al. Swiss group for clinical cancer research (SAKK). Concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer: 10-year follow-up of a randomized phase III trial (SAKK 10/94). Int J Radiat Oncol Biol Phys. 2012;82:524–31.

    Article  PubMed  CAS  Google Scholar 

  53. Mouw KW, Haraf DJ, Stenson KM, et al.: Factors associated with long-term speech and swallowing outcomes after chemoradiotherapy for locally advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 2010,136:1226–1234. Important topic emerged in the past decade but with a definitive impact on quality of life of long-term survivors.

    Article  PubMed  Google Scholar 

  54. Russi E, Corvò R, Merlotti A, et al.: Swallowing dysfunction in head and neck cancer patients treated by radiotherapy: review and recommendations of the supportive task group of the Italian Association of Radiation Oncology. Cancer Treat Rev 2012,38:1033–1049. Useful literature review on swallowing disfunction including in-depth pathophysiologic analysis. The authors also give important practical recommendation.

    Article  PubMed  Google Scholar 

  55. Nguyen NP, Chi A, Nguyem LN, et al. Human papilloma virus-associated oropharyngeal cancer: a new clinical entity. Q J Med. 2010;103:229–36.

    Article  CAS  Google Scholar 

  56. Marklund L, Hammarstedt L. Impact of HPV in oropharyngeal cancer. J Oncol. 2011. doi:10.1155/2011/509036.

    PubMed  Google Scholar 

  57. Attner P, Du J, Nasman A, et al. Human papillomavirus and survival in patients with base of the tongue cancer. Int J Cancer. 2011;128:2892–7.

    Article  PubMed  CAS  Google Scholar 

  58. Isayeva T, Li Y, Mashawahu D, et al.: Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head and Neck Pathol. 2012;(Suppl 1):S104–120.

  59. Ang KK, Harris J, Wheeler R, et al.: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35. A cornerstone study establishing a new prognostic score for head and neck cancer patients.

    Article  PubMed  CAS  Google Scholar 

  60. Marur S, Li S, Cmelak A, et al. Eastern Cooperative Oncology Group E 1308: A phase II trial of induction chemotherapy followed by cetuximab with low dose versus standard dose IMRT in patients with human papilloma virus (HPV) associated resectable squamous cell carcinoma of oropharynx (OPSCC). J Clin Oncol. 2013;31(S15):6005.

    Google Scholar 

Download references

Conflict of Interest

Nerina Denaro and Elvio G. Russi declare that they have no conflict of interest.

Marco C. Merlano has board membership with Merck Serono and Amgen, has provided expert testimony for Merck Serono, and had travel/accommodations expenses covered or reimbursed by Merck Serono and Novartis.

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.

Author information

Authors and Affiliations

  1. Department of Clinical Oncology, Medical Oncology, S. Croce Genereal Hospital, via Coppino 26, 12100, Cuneo, Italy

    Nerina Denaro MD

  2. Department of Clinical Oncology, Radiotherapy, S. Croce Genereal Hospital, via Coppino 26, 12100, Cuneo, Italy

    Elvio G. Russi MD & Marco C. Merlano MD

Authors
  1. Nerina Denaro MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elvio G. Russi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco C. Merlano MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco C. Merlano MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Denaro, N., Russi, E.G. & Merlano, M.C. Strategies for Non-Resectable Head and Neck Cancer. Curr. Treat. Options in Oncol. 14, 492–504 (2013). https://doi.org/10.1007/s11864-013-0260-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-013-0260-6

Keywords

Search

Navigation