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Alteration of radiotherapy fractionation and concurrent chemotherapy: a new frontier in head and neck oncology?

Nature Clinical Practice Oncology volume 2, pages 305–314 (2005)Cite this article

Abstract

Despite recent advances in multimodality management of patients with stage III–IV head and neck squamous cell carcinoma, the prognosis in these patients remains disappointing. In an attempt to improve treatment outcome, several teams recently investigated the role of altered fractionation radiotherapy in conjunction with systemic chemotherapy. The controlled trials that investigated this combined approach indicate that, although the magnitude of its effect was less marked for survival indices than for local-regional control, the addition of chemotherapy to altered fractionation regimens results in a clear improvement for these endpoints compared with hyperfractionated or accelerated regimens alone. The key challenge now is to optimize the synergism of these regimens in order to increase their therapeutic ratio in terms of both local-regional and systemic outcomes. This review is a critical appraisal of the real opportunities offered by the application of treatments aimed at increasing the dose intensity of radiotherapy delivered concurrently with cytotoxic drugs.

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References

  1. Parkin DM et al. (1992) Cancer incidence in five continents, vol. 6. Lyon: IARC

    Google Scholar 

  2. Bataini JP et al. (1988) Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radiocurability of neck nodes. Int J Radiat Oncol Biol Phys 14: 635–642

    Article  CAS  Google Scholar 

  3. Hall EJ (1994) Radiobiology for the radiologist, edn 4. Philadelphia: Lippincott

    Google Scholar 

  4. Withers HR et al. (1988) The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 27: 131–146

    Article  CAS  Google Scholar 

  5. Horiot JC et al. (1992) Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25: 231–241

    Article  CAS  Google Scholar 

  6. Dische S et al. (1997) A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol 44: 123–136

    Article  CAS  Google Scholar 

  7. Horiot JC et al. (1997) Accelerated fractionation (AF) compared to conventional fractionation (CF) improves locoregional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol 44: 111–121

    Article  CAS  Google Scholar 

  8. Vermorken JB (1992) Adjuvant chemotherapy for advanced squamous cell carcinomas of the head and neck. In Multimodality therapy for head and neck cancer, 112–126 (Eds Snow GB and Clark JR) New York: Georg Thieme Verlag

    Google Scholar 

  9. Fu KK et al. (1987) Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial. J Clin Oncol 5: 1410–1418

    Article  CAS  Google Scholar 

  10. Harrison LD et al. (1991) Concomitant chemotherapy and radiation therapy for advanced unresectable head and neck cancer. Int J Radiat Oncol Biol Phys 21: 703–708

    Article  CAS  Google Scholar 

  11. Herscher LL et al. (1999) Principles of chemoradiation: theoretical and practical considerations. Oncology 13 (10 Suppl 5): 11–22

    CAS  PubMed  Google Scholar 

  12. Douple EB (1988) Platinum-radiation interactions. NCI Monogr 6: 315–319

    Google Scholar 

  13. Cooper JS and Ang KK (2005) Concomitant chemotherapy and radiation therapy certainly improves local control. Int J Radiat Oncol Biol Phys 61: 7–9

    Article  Google Scholar 

  14. Vokes EE and Weichselbaum RR (1990) Radiotherapy with concomitant chemotherapy for head and neck cancer. J Clin Oncol 8: 911–934

    Article  CAS  Google Scholar 

  15. Marcial VA et al. (1990) Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous-cell carcinomas of the head and neck. Cancer 66: 1861–1868

    Article  CAS  Google Scholar 

  16. Bernier J and Bentzen SM (2003) Altered fractionation and combined radio-chemotherapy approaches: pioneering new opportunities in head and neck oncology. Eur J Cancer 39: 560–571

    Article  CAS  Google Scholar 

  17. Ang KK (1998) Altered fractionation trials in head and neck cancer. Semin Radiat Oncol 8: 230–236

    Article  CAS  Google Scholar 

  18. Peters LJ et al. (1992) Altered fractionation schedules. In Principles and practice of radiation oncology, 2nd edn, 97–113 (Eds Perez CA and Brady LW) Philadelphia: J.B. Lippincott

    Google Scholar 

  19. Mendenhall WM et al. (2003) Altered fractionation and/or adjuvant chemotherapy in definitive irradiation of squamous cell carcinoma of the head and neck. Laryngoscope 113: 546–551

    Article  Google Scholar 

  20. Bourhis et al. (2004) Meta-analysis of conventional versus altered fractionated radiotherapy: in head and neck squamous cell carcinomas (HNSCC): final analysis. 46th American Society of Therapeutic Radiology and Oncology (ASTRO) meeting, 3–7 October 2004, Atlanta. Int J Rad Oncol Biol Phys 60 (Suppl): S190–S191

    Article  Google Scholar 

  21. Forastiere AA 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

    Article  CAS  Google Scholar 

  22. Jacobs C 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

    Article  CAS  Google Scholar 

  23. Dewit L (1987) Combined treatment of radiation and cis-diamminedichloroplatinum (II): a review of experimental and clinical data. Int J Radiat Oncol Biol Phys 13: 403–426

    Article  CAS  Google Scholar 

  24. Stell PM and Rawson NS (1990) Adjuvant chemotherapy in head and neck cancer. Br J Cancer 61: 779–787

    Article  CAS  Google Scholar 

  25. Munro AJ (1995) An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer. Br J Cancer 71: 83–91

    Article  CAS  Google Scholar 

  26. El Sayed S and Nelson N (1996) Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region. A meta-analysis of prospective and randomized trials. J Clin Oncol 14: 838–847

    Article  CAS  Google Scholar 

  27. Pignon JP et al. (2000) 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: 949–955

    Article  CAS  Google Scholar 

  28. Browman GP et al. (2001) Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis. Head Neck 23: 579–589

    Article  CAS  Google Scholar 

  29. Bourhis J et al. on behalf of the MACH-NC Collaborative Group (2004). Update of MACH-NC (Meta-Analysis of Chemotherapy in Head & Neck Cancer) database focused on concomitant chemoradiotherapy. Proc Am Soc Clin Oncol 22 (Suppl): S5505

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. Brizel DM et al. (1998) Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338: 1798–1804

    Article  CAS  Google Scholar 

  32. Dobrowsky W and Naude J (2000) Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancers. Radiother Oncol 57: 119–124

    Article  CAS  Google Scholar 

  33. Jeremic B et al. (2000) Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18: 1458–1464

    Article  CAS  Google Scholar 

  34. Staar S et al. (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. Int J Radiat Oncol Biol Phys 50: 1161–1171

    Article  CAS  Google Scholar 

  35. Huguenin P et al. (2004) Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy. J Clin Oncol 22: 4665–4673

    Article  CAS  Google Scholar 

  36. Budach V et al. (2005) Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial. J Clin Oncol 23: 1125–1135

    Article  CAS  Google Scholar 

  37. Adelstein DJ 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  Google Scholar 

  38. Vokes EE et al. (2003) Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: Curative and organ-preserving therapy for advanced head and neck cancer. J Clin Oncol 21: 320–326

    Article  Google Scholar 

  39. Rischin D et al. (2005) Tirapazamine, cisplatin, and radiation versus fluorouracil, cisplatin, and radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02). J Clin Oncol 23: 79–87

    Article  CAS  Google Scholar 

  40. Bonner JA et al. (2004) ASCO 2004 Annual Meeting Proceedings 5507 (Suppl): S489

  41. Chao KS et al. (2003) Toxicity profile of intensity-modulated radiation therapy for head and neck carcinoma and potential role of amifostine. Sem Oncol 30: 101–108

    Article  CAS  Google Scholar 

  42. Lawrence TS et al. (2003) The Mechanism of action of radiosensitization of conventional chemotherapeutic agents. Semin Rad Oncol 13: 13–21

    Article  Google Scholar 

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Authors and Affiliations

  1. Chairman in the Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    Jacques Bernier

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  1. Jacques Bernier
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Correspondence to Jacques Bernier.

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Glossary

THERAPEUTIC RATIO

Defines the difference between a minimum therapeutically effective dose and a maximum dose capable of inducing intolerable side effects; the difference between the minimum and maximum effective doses; also known as therapeutic window

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Bernier, J. Alteration of radiotherapy fractionation and concurrent chemotherapy: a new frontier in head and neck oncology?. Nat Rev Clin Oncol 2, 305–314 (2005). https://doi.org/10.1038/ncponc0201

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