Head and neck cancer: a step forward

  • S. Jelic
  • I. Popov
  • V. H. Schartinger
  • G. M. Sprinzl
Short review


Head and neck cancers have for a long time been orphan cancers for any trials of individualized treatment, at least in part because the number of active cytotoxic drugs has been for a long time rather restricted. Histology did not influence treatment modality and the use of particular cytotoxic drugs. Undifferentiated carcinoma of the nasopharynx was the first tumour type to enhance investigations in individualized treatment, as regards to choice of cytotoxic drugs and combinations of chemo and radiotherapy. Recently the HPV16/18 positive carcinoma of the oropharynx has arisen as a topic for individualized approach. The biologicals are relatively late newcomers in the arsenal of drugs available for head and neck cancer. The same statement is related to research of possible targets and thus investigations of subpopulations that might benefit from a particular drug or a particular pathway inhibition. Individualized drug treatment in head and neck cancer appears to be at its promising beginnings.


Head and neck cancer Chemotherapy Targeted therapies Personalized medicine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Budach W, Hehr T, Budach V, Belka C, Dietz K. 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, 6: 28, 2006CrossRefPubMedGoogle Scholar
  2. Pignon JP, Bourhis J, Domenge C, Designe L. 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, 355(9208): 949–955, 2000PubMedGoogle Scholar
  3. Pignon JP, Le Maitre A, Bourhis J. Meta-analyses of chemotherapy in head and neck cancer (MACH-NC): an update. Int J Radiat Oncol Biol Phys, 69(2 Suppl): S112–S114, 2007PubMedGoogle Scholar
  4. Bernier J. A multidisciplinary approach to squamous cell carcinomas of the head and neck: an update. Curr Opin Oncol, 20(3): 249–255, 2008CrossRefPubMedGoogle Scholar
  5. Dimery IW, Hong WK. Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst, 85(2): 95–111, 1993CrossRefPubMedGoogle Scholar
  6. Forastiere AA. Overview of platinum chemotherapy in head and neck cancer. Semin Oncol, 21(5 Suppl 12): 20–27, 1994PubMedGoogle Scholar
  7. Jassem J, Gyergyay F, Kerpel-Fronius S, Nagykalnai T, Baumohl J, Verweij J, et al. Combination of daily 4-h infusion of 5-fluorouracil and cisplatin in the treatment of advanced head and neck squamous-cell carcinoma: a South-East European Oncology Group study. Cancer Chemother Pharmacol, 31(6): 489–494, 1993CrossRefPubMedGoogle Scholar
  8. Kim JG, Sohn SK, Kim DH, Baek JH, Jeon SB, Chae YS, et al. Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck. Br J Cancer, 93(10): 1117–1121, 2005CrossRefPubMedGoogle Scholar
  9. Bentzen JD, Hansen HS. Phase II analysis of paclitaxel and capecitabine in the treatment of recurrent or disseminated squamous cell carcinoma of the head and neck region. Head Neck, 29(1): 47–51, 2007CrossRefPubMedGoogle Scholar
  10. Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet, 368(9538): 843–854, 2006CrossRefPubMedGoogle Scholar
  11. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med, 350(19): 1945–1952, 2004CrossRefPubMedGoogle Scholar
  12. Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med, 357(17): 1705–1715, 2007CrossRefPubMedGoogle Scholar
  13. Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med, 357(17): 1695–1704, 2007CrossRefPubMedGoogle Scholar
  14. Hitt R, Grau J, Lopez-Pousa A, Berrocal A, Garcia-Giron C, Belon J, et al. Randomized phase II/III clinical trial of induction chemotherapy (ICT) with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin/5-fluorouracil (TPF) followed by chemoradiotherapy (CRT) vs. crt alone for patients (pts) with unresectable locally advanced head and neck cancer (LAHNC). J Clin Oncol (Meeting Abstracts), 24(18 Suppl): 5515, 2006Google Scholar
  15. Paccagnella A, Buffoli A, Koussis H, Gava A, Franceschi T, Gardani G, et al. Concomitant chemoradiotherapy (CT/RT) vs neoadjuvant chemotherapy with docetaxel/cispaltin/5-fluorouracil (TPF) followed by CT/RT in locally advanced head and neck cancer. Final results of a phase II randomized study. J Clin Oncol (Meeting Abstracts), 26(15 Suppl): 6000, 2008Google Scholar
  16. Berek JS, Schink JC, Knox RM. Synergistic effect of combined intraperitoneal cisplatin and cytosine arabinoside in a murine ovarian cancer model. Obstet Gynecol, 74(4): 663–666, 1989PubMedGoogle Scholar
  17. Kohno N, Ohnuma T, Biller HF, Holland JF. Effects of cisplatin plus fluorouracil vs cisplatin plus cytarabine on head and neck squamous multicellular tumor spheroids. Arch Otolaryngol Head Neck Surg, 114(2): 157–161, 1988PubMedGoogle Scholar
  18. Craig JB, Powell BL, Jackson DV, Atkins JN, Smith LR, White DR, et al. Phase II trial of high-dose cytarabine and cisplatin in locoregional previously untreated squamous carcinoma of the head and neck: a Piedmont Oncology Association Study. Cancer Treat Rep, 71(2): 151–153, 1987PubMedGoogle Scholar
  19. Jelic S, Mitrovic L, Kovcin V, Nikolic-Tomasevic Z, Radulovic S, Tomasevic Z, et al. Modulation of cisplatin antitumor activity by short infusional high-dose cytosine arabinoside in advanced pretreated head and neck carcinoma: a phase II study. J Chemother, 8(4): 304–309, 1996PubMedGoogle Scholar
  20. Powell BL, Craig JB, Muss HB, Zekan PJ, Cooper MR, Schnell FM, et al. Phase II trial of high-dose cytosine arabinoside and cisplatin in recurrent squamous carcinoma of the head and neck. A Piedmont Oncology Association Study. Am J Clin Oncol, 11(5): 550–552, 1988CrossRefPubMedGoogle Scholar
  21. Stewart DJ, Maroun JA, Laframboise G, Gerin-Lajoie J. Cisplatin plus cytosine arabinoside in the treatment of squamous cell carcinoma of the head and neck. Am J Clin Oncol, 9(3): 200–203, 1986CrossRefPubMedGoogle Scholar
  22. Jelic S, Stamatovic L, Vucicevic S, Petrovic Z, Kreacic M, Babovic N, et al. Use of high-dose cytarabine to enhance cisplatin cytotoxicity-effects on the response and overall survival rates of advanced head and neck cancer patients. Eur J Cancer, 38(11): 1478–1489, 2002CrossRefPubMedGoogle Scholar
  23. Ponzanelli A, Vigo V, Marcenaro M, Bacigalupo A, Gatteschi B, Ravetti JL, et al. Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results. Oral Oncol, 44(8): 767–774, 2008CrossRefPubMedGoogle Scholar
  24. Azli N, Fandi A, Bachouchi M, Rahal M, Lianes P, Wibault P, et al. Final report of a phase II study of chemotherapy with bleomycin, epirubicin, and cisplatin for locally advanced and metastatic/recurrent undifferentiated carcinoma of the nasopharyngeal type. Cancer J Sci Am, 1(3): 222–229, 1995PubMedGoogle Scholar
  25. Jelic S, Kovcin V, Milanovic N, Kreacic M, Pendjer I, Jovanovic V, et al. Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT). Ann Oncol, 8(8): 739–744, 1997CrossRefPubMedGoogle Scholar
  26. Jelic S, Nikolic-Tomasevic Z, Kovcin V, Milanovic N, Tomasevic Z, Jovanovic V, et al. A two-step reevaluation of high-dose amsacrine for advanced carcinoma of the upper aerodigestive tract: a pilot phase II study. J Chemother, 9(5): 364–370, 1997PubMedGoogle Scholar
  27. Klussmann JP, Preuss SF, Speel EJ. Human papillomavirus and cancer of the oropharynx. Molecular interaction and clinical implications. HNO, 57(2): 113–122, 2009CrossRefPubMedGoogle Scholar
  28. Syrjanen S. Human papillomaviruses in head and neck carcinomas. N Engl J Med, 356(19): 1993–1995, 2007CrossRefPubMedGoogle Scholar
  29. Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, et al. 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, 2002PubMedGoogle Scholar
  30. Schartinger VH, Kacani L, Andrle J, Schwentner I, Wurm M, Obrist P, et al. Pharmacodiagnostic value of the HER family in head and neck squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec, 66(1): 21–26, 2004PubMedGoogle Scholar
  31. Rubin GJ, Melhem MF, Gooding WE, Day R, Holst VA, Wagener MM, et al. 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, 1998CrossRefGoogle Scholar
  32. Karamouzis MV, Grandis JR, Argiris A. Therapies directed against epidermal growth factor receptor in aerodigestive carcinomas. JAMA, 298(1): 70–82, 2007CrossRefPubMedGoogle Scholar
  33. Shepherd FA, Rodrigues PJ, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med, 353(2): 123–132, 2005CrossRefPubMedGoogle Scholar
  34. Thatcher N, Chang A, Parikh P, Rodrigues PJ, Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet, 366(9496): 1527–1537, 2005CrossRefPubMedGoogle Scholar
  35. Stewart JS, Cohen EE, Licitra L, Van Herpen CM, Khorprasert C, Soulieres D, et al. Phase III study of gefitinib 250 compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol, 27(11): 1864–1871, 2009CrossRefPubMedGoogle Scholar
  36. Abidoye OO, Cohen EE, Wong SJ, Kozloff MF, Nattam SR, Stenson KM, et al. A phase II study of lapatinib (GW572016) in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol (Meeting Abstracts), 24(18 Suppl): 5568, 2006Google Scholar
  37. Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS, Siu LL. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol, 22(1): 77–85, 2004CrossRefPubMedGoogle Scholar
  38. Arteaga ME, Ledon N, Casaco A, Pardo B, Garcia M, Boleda M, et al. Systemic and skin toxicity in Cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti-epidermal growth factor receptor monoclonal antibody Nimotuzumab. Cancer Biol Ther, 6(9): 1390–1395, 2007CrossRefPubMedGoogle Scholar
  39. Rojo F, Gracias E, Villena N, Cruz T, Corradino I, Cedeno M, et al. Pharmacodynamic study of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN): a SENDO Foundation study. J Clin Oncol (Meeting Abstracts), 26(15 Suppl): 6070, 2008Google Scholar
  40. Rivera F, Vega-Villegas ME, Lopez-Brea MF, Marquez R. Current situation of panitumumab, matuzumab, nimotuzumab and zalutumumab. Acta Oncol, 47(1): 9–19, 2008CrossRefPubMedGoogle Scholar
  41. Burtness B. The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Expert Opin Biol Ther, 5(8): 1085–1093, 2005CrossRefPubMedGoogle Scholar
  42. Rathcke IO, Gottschlich S, Gorogh T, Lippert BM, Werner JA. Incidence of point mutations in Ki-ras codon 12 and 13 in squamous epithelial carcinomas of the head-neck region. Laryngorhinootologie, 75(8): 465–470, 1996CrossRefPubMedGoogle Scholar
  43. Rizos E, Sourvinos G, Arvanitis DA, Velegrakis G, Spandidos DA. Low incidence of H-, K- and N-ras oncogene mutations in cytological specimens of laryngeal tumours. Oral Oncol, 35(6): 561–563, 1999CrossRefPubMedGoogle Scholar
  44. Vermorken JB, Mesia R, Vega-Villegas ME, Remenar E, Hitt R, Kawecki A, et al. Cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil (5-FU) in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R&M SCCHN) (EXTREME). J Clin Oncol (Meeting Abstracts), 24(18 Suppl): 5537, 2006Google Scholar
  45. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med, 354(6): 567–578, 2006CrossRefPubMedGoogle Scholar
  46. Chan AT, Hsu MM, Goh BC, Hui EP, Liu TW, Millward MJ, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol, 23(15): 3568–3576, 2005CrossRefPubMedGoogle Scholar
  47. Diaz MA, Blanco R, Garcia B, Badia T, Batista AE, Alonso R, et al. Biological activity in vitro of anti-epidermal growth factor receptor monoclonal antibodies with different affinities. Hybridoma (Larchmt), 26(6): 423–431, 2007CrossRefGoogle Scholar
  48. Kalish LH, Kwong RA, Cole IE, Gallagher RM, Sutherland RL, Musgrove EA. Deregulated cyclin D1 expression is associated with decreased efficacy of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in head and neck squamous cell carcinoma cell lines. Clin Cancer Res, 10(22): 7764–7774, 2004CrossRefPubMedGoogle Scholar
  49. Yoshida T, Okamoto I, Okabe T, Iwasa T, Satoh T, Nishio K, et al. Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Int J Cancer, 122(7): 1530–1538, 2008CrossRefPubMedGoogle Scholar
  50. Erjala K, Sundvall M, Junttila TT, Zhang N, Savisalo M, Mali P, et al. Signaling via ErbB2 and ErbB3 associates with resistance and epidermal growth factor receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells. Clin Cancer Res, 12(13): 4103–4111, 2006CrossRefPubMedGoogle Scholar
  51. Huang S, Armstrong EA, Benavente S, Chinnaiyan P, Harari PM. Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res, 64(15): 5355–5362, 2004CrossRefPubMedGoogle Scholar
  52. Specenier P, Vermorken JB. The role of taxanes and targeted therapies in locally advanced head and neck cancer. Curr Opin Oncol, 19(3): 195–201, 2007CrossRefPubMedGoogle Scholar
  53. Fujita K, Sano D, Kimura M, Yamashita Y, Kawakami M, Ishiguro Y, et al. Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma. Oncol Rep, 18(1): 47–51, 2007PubMedGoogle Scholar
  54. Seiwert TY, Haraf DJ, Cohen EE, Stenson K, Witt ME, Dekker A, et al. Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J Clin Oncol, 26(10): 1732–1741, 2008CrossRefPubMedGoogle Scholar
  55. Amornphimoltham P, Patel V, Leelahavanichkul K, Abraham RT, Gutkind JS. A retroinhibition approach reveals a tumor cell-autonomous response to rapamycin in head and neck cancer. Cancer Res, 68(4): 1144–1153, 2008CrossRefPubMedGoogle Scholar
  56. Aissat N, Le Tourneau C, Ghoul A, Serova M, Bieche I, Lokiec F, et al. Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck cancer cell lines. Cancer Chemother Pharmacol, 62(2): 305–313, 2008CrossRefPubMedGoogle Scholar
  57. Bussink J, van der Kogel AJ, Kaanders JH. Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol, 9(3): 288–296, 2008CrossRefPubMedGoogle Scholar
  58. Zhang PL, Pellitteri PK, Law A, Gilroy PA, Wood GC, Kennedy TL, et al. Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis. Mod Pathol, 18(7): 924–932, 2005CrossRefPubMedGoogle Scholar
  59. Macdonald GC, Rasamoelisolo M, Entwistle J, Cuthbert W, Kowalski M, Spearman MA, et al. A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck. Med Oncol, 26(3): 257–264, 2008CrossRefPubMedGoogle Scholar
  60. Schartinger VH, Schmutzhard J, Wurm M, Schwentner I, Obrist P, Oberaigner W, et al. The expression of EGFR, HER2 and EpCam in head and neck squamous cell carcinomas. memo, 2(1): 45–50, 2009CrossRefGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • S. Jelic
    • 1
  • I. Popov
    • 1
  • V. H. Schartinger
    • 2
  • G. M. Sprinzl
    • 2
  1. 1.Institute for Oncology and Radiology of SerbiaClinic of Medical OncologyBelgradeSerbia
  2. 2.Department of Otorhinolaryngology, Head and Neck SurgeryInnsbruck Medical UniversityInnsbruckAustria

Personalised recommendations