International Journal of Radiation Oncology * Biology * Physics
Volume 50, Issue 5 , Pages 1161-1171 , 1 August 2001

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy—results of a multicentric randomized German trial in advanced head-and-neck cancer

  • Susanne Staar, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Cologne, Cologne, Germany
    • Corresponding Author InformationReprint requests to: Dr. Susanne Staar, Klinik fuer Strahlentherapie der Universitaet zu Koeln, Joseph-Stelzmann-Str. 9, 50933 Koeln, Germany. Tel: +49-221-478 5449; Fax: +49-221-478 6158
  • ,
  • Volker Rudat, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany
  • ,
  • Hartmut Stuetzer, M.D.

      Affiliations

    • Department of Medical Statistics and Epidemiology, University of Cologne, Cologne, Germany
  • ,
  • Andreas Dietz, M.D.

      Affiliations

    • Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany
  • ,
  • Peter Volling, M.D.

      Affiliations

    • Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Oldenburg, Oldenburg, Germany
  • ,
  • Michael Schroeder, M.D.

      Affiliations

    • Department of Oto-Rhino-Laryngology, Head and Neck Surgery, City Hospital Kassel, Kassel, Germany
  • ,
  • Michael Flentje, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany
  • ,
  • Hans Edmund Eckel, M.D.

      Affiliations

    • Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
  • ,
  • Rolf-Peter Mueller, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Cologne, Cologne, Germany

,Accepted 23 February 2001.

References 

  1. Million RR, Cassisi NJ. Management of head and neck cancer. A multidisciplinary approach. Philadelphia: JB Lippincott; 1994;
  2. Marcial VA, Pajak TF. Radiation therapy alone or in combination with surgery in head and neck cancer. Cancer. 1989;55:2259–2265
  3. Gupta NK, Pointon RCS, Wilkonson PM. A randomized clinical trial to contrast radiotherapy with radiotherapy and methotrexate given synchronously in head and neck cancer. Cancer Radiol. 1987;38:575–581
  4. Pinto LH, Canary PC, Araujo CM, et al.  Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1991;21:557–562
  5. Horiot JC, LeFur R, Nguyen T, et al.  EORTC cooperative group of radiotherapy   Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma (Final analysis of a randomized trial of the). Radiother Oncol. 1992;225:231–241
  6. Ang KK. Altered fractionation trials in head and neck cancer. Semin Rad Oncol. 1998;8:230–236
  7. Forastiere AA, Trotti A. Radiotherapy and concurrent chemotherapy (A strategy that improves locoregional control and survival in oropharyngeal cancer). J Natl Cancer Inst. 1999;91:2065–2066
  8. Harari PM. Why has induction chemotherapy for advanced head and neck cancer become a United States community standard of practice?. J Clin Oncol. 1997;15:2050–2055
  9. Jeremic B, Shibamoto Y, Stanislavjevic B, et al.  Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck (A prospective randomized trial). Radiother Oncol. 1997;43:29–37
  10. Haselow RE, Warshaw MG, Okin MM, et al.  Radiation alone versus radiation plus weekly low-dose cisplatinum in unresectable cancer of the head and neck. In:  Free WE,  Goepfert H,  Johns ME, et al. editor. Head and neck cancer. 1st ed.. Toronto: Marcel Dekker; 1990;p. 279–281
  11. Browman GP, Cripps C, Hodson D, et al.  Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol. 1994;12:2648–2653
  12. Taylor SG, Murthy AK, Vannetzel JM, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 1994:385–395.
  13. Merlano M, Vitale V, Roso R, et al.  Treatment of advanced squamous cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. N Engl J Med. 1992;327:1115–1121
  14. Bourhis J, Pignon JP. Meta-analysis in head and neck squamous cell carcinoma. What is the role of chemotherapy?. Hematol Oncol Clin North Am. 1999;13:769–775
  15. Withers HR, Taylor JMG, Macejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27:131–146
  16. Peters LJ, Ang KK, Mames HD. Accelerated fractionation in the radiation treatment of head and neck cancer. Acta Oncol. 1988;27:185–194
  17. Fowler JF. The linear-quadratic formula and program in fractionated radiotherapy. Br J Radiol. 1989;62:679–694
  18. Sladowski K, Macejewski B, Pileski B, et al.  Randomized clinical trial of accelerated 7 days per week fractionation in radiotherapy for head and neck cancer. Preliminary report on therapy toxicity. Radiother Oncol. 1996;40:40
  19. Overgaard J, Sand Hansen H, Sapru W, et al.  Conventional radiotherapy as the primary treatment of squamous cell carcinoma (SCC) of the head and neck. A randomized multicenter study of 5 versus 6 fractions per week - preliminary report from DAHANCA 6 and 7 trial. Radiother Oncol. 1996;40:531
  20. Jackson SM, Weir LM, Hay JH, et al.  A randomized trial of accelerated versus conventional radiotherapy in head and neck cancer. Radiother Oncol. 1997;43:39–46
  21. Ang KK, Peters LJ, Weber R. Concomitant boost radiotherapy schedules in the treatment of carcinoma of the oropharynx and nasopharynx. Int J Radiat Oncol Biol Phys. 1990;19:1339–1345
  22. Staar S, Rudat V, Volling P, et al.  Results of a German multicentric trial of accelerated hyperfractionated radiochemotherapy in advanced head and neck cancer. Radiother Oncol. 1996;40(Suppl.1):14
  23. Bjordal K, Ahlner-Elmquist M, Tollesson E, et al.  on behalf of the EORTC Quality of Life Study group   Development of a European Organization for Research and Treatment of Cancer (EORTC) questionnaire module to be used in quality of life assessments in head and neck cancer patients. Acta Oncologica. 1994;33:879–885
  24. Hosmer DW, Lemeshow S. Applied survival analysis. Regression modeling of time to event data. New York: Wiley & Sons, Inc; 1999;
  25. Cox DR, Oakes D. Analysis of survival data. London: Chapman Hall; 1984;
  26. Cox JD, Steztz J, Pajak TF  Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) . Int J Radiat Oncol Biol Phys. 1995;31:1341–1346
  27. Seegenschmiedt MH. Interdisciplinary documentation of treatment side effects in oncolgy. Present status and perspectives. Strahlenther Onkol. 1998;174(Suppl. 3):25–29
  28. Haffty BG, Son YH, Papak R, et al.  Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck (Results of the Yale mitomycin randomized trials). J Clin Oncol. 1997;15:268–276
  29. Gabriele P, Orecchia R, Ragona R, et al.  A cooperative AIRO/Piemonte randomized clinical trial of carboplatin as an adjunct to radiotherapy in head and neck cancer. Radiother Oncol. 1994;32(Suppl.):S93
  30. Adelstein DJ, Lavertu P, Saxton JP, et al.  Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy (RT) alone in resectable stage III and IV squamous cell head and neck cancer (SCHNC) (Abstr.). Head Neck. 1998;20:444
  31. Calais G, Alfonsi M, Bardet E, et al.  Randomized trial of radiation therapy versus concomitant chemoradiotherapy and radiation therapy for advanced advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999;91:2081–2086
  32. Fu KK, Pajak TF, Trotti A, et al.  Radiation Therapy Oncology Group (RTOG)   A phase III randomized study to compare hyperfractionation, and two variants of accelerated fractionation to standard fractionation radiotherapy for head, and neck suqamous cell carcinoma. Preliminary results of RTOG 9003 (Abstr.). Int J Radiat Oncol Biol Phys. 1999;45(Suppl.):145
  33. Glicksman AS, Wanebo HJ, Slotman G, et al.  Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 1997;39:721–729
  34. MacKenzie R, Balogh J, Choo R, et al.  Accelerated radiotherapy with delayed concomitant boost in locally advanced squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1999;45:589–595
  35. Wendt TG, Grabenbauer GG, Rodel CM, et al.  Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer (A randomized multicenter study). J Clin Oncol. 1998;16:1318–1324
  36. Dobrowsky WH, Naude J, Widder J, et al.  Continuous hyperfractionated accelerated radiotherapy and mitomycin C in head and neck cancer (Abstr.). Int J Radiat Oncol Biol Phys. 1999;45(Suppl.):7
  37. Vokes EE, Kies MS, Haraf DJ, et al.  Concomitant chemoradiotherapy as primary therapy for locoregional advanced head and neck cancer. J Clin Oncol. 2000;18:1652–1661
  38. Brizel DM, Albers ME, Fisher SR, et al.  Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanved head and neck cancer. N Engl J Med. 1998;338:1798–1804
  39. Vokes EE, Haraf DJ, Mick R, et al.  Intensified concomitant chemoradiotherapy with and without filgrastim for poor-prognostic head and neck cancer. J Clin Oncol. 1994;12:2351–2359
  40. Tsuzuki H, Fujieda S, Sunaga H, et al.  Expression of granulocyte colony-stimulating factor receptor correlates with prognosis in oral and mesopharyngeal carcinoma. Cancer Res. 1998;58:794–800
  41. Noda I, Fujieda S, Ohtsubo T, et al.  Granulocyte-colony-stimulating factor enhances invasive potential of human head-and-neck-carcinoma cell lines. Int J Cancer. 1999;80:78–84
  42. Butler EB, Teh BS, Grant WH, et al.  SMART (Simultaneous Modulated Accelerated Radiation Therapy Boost). A new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys. 1999;45:21–32

 Supported by “Deutsche Krebshilfe.”

PII: S0360-3016(01)01544-9

International Journal of Radiation Oncology * Biology * Physics
Volume 50, Issue 5 , Pages 1161-1171 , 1 August 2001