Skip to main content
Top
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

Authors: Reinhold Graf, Bert Hildebrandt, Wolfgang Tilly, Hanno Riess, Roland Felix, Volker Budach, Peter Wust

Published in: BMC Cancer | Issue 1/2006

Login to get access

Abstract

Background

The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy.

Methods

Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987–1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared.

Results

Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups.

Conclusion

Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival.
Appendix
Available only for authorised users
Literature
1.
go back to reference Stuschke M, Thames H: Hyperfractionation: where do we stand?. Radiother Oncol. 1998, 46: 131-33. 10.1016/S0167-8140(97)00181-3.CrossRefPubMed Stuschke M, Thames H: Hyperfractionation: where do we stand?. Radiother Oncol. 1998, 46: 131-33. 10.1016/S0167-8140(97)00181-3.CrossRefPubMed
2.
go back to reference Adelstein DJ, Sharan VM, Earle AS, Shah AC, Vlastou C, Haria CD, Damm C, Carter SG, Hines JD: Concomitant versus sequential combined technique therapy for squamous cell head and neck cancer. Cancer. 1990, 65: 1685-91.CrossRefPubMed Adelstein DJ, Sharan VM, Earle AS, Shah AC, Vlastou C, Haria CD, Damm C, Carter SG, Hines JD: Concomitant versus sequential combined technique therapy for squamous cell head and neck cancer. Cancer. 1990, 65: 1685-91.CrossRefPubMed
3.
go back to reference Wendt TG, Grabenbauer GG, Rodel CM, Thiel HJ, Aydin H, Rohloff R, Wustrow TP, Iro H, Popella C, Schalhorn A: Concomitant radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol. 1998, 16: 1318-24.PubMed Wendt TG, Grabenbauer GG, Rodel CM, Thiel HJ, Aydin H, Rohloff R, Wustrow TP, Iro H, Popella C, Schalhorn A: Concomitant radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol. 1998, 16: 1318-24.PubMed
4.
go back to reference Budach V, Stuschke M, Budach W, Baumann M, Geismar D, Grabenbauer G, Lammert I, Jahnke K, Stueben G, Herrmann T, Bamberg M, Wust P, Hinkelbein W, Wernecke KD: 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. 2005, 23: 1125-1135. 10.1200/JCO.2005.07.010.CrossRefPubMed Budach V, Stuschke M, Budach W, Baumann M, Geismar D, Grabenbauer G, Lammert I, Jahnke K, Stueben G, Herrmann T, Bamberg M, Wust P, Hinkelbein W, Wernecke KD: 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. 2005, 23: 1125-1135. 10.1200/JCO.2005.07.010.CrossRefPubMed
5.
go back to reference 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. 2000, 355: 949-55.CrossRefPubMed 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. 2000, 355: 949-55.CrossRefPubMed
6.
go back to reference Spiessl B, Beahrs OH, Hermanek P, Hutter RV, Scheibe O, Sobin LH, Wagner G: TNM atlas. Illustrated guide to the TNM/pTNM classification of malignant tumors (ed 3, 2nd rev). 1992, Berlin, Germany, Springer-Verlag Spiessl B, Beahrs OH, Hermanek P, Hutter RV, Scheibe O, Sobin LH, Wagner G: TNM atlas. Illustrated guide to the TNM/pTNM classification of malignant tumors (ed 3, 2nd rev). 1992, Berlin, Germany, Springer-Verlag
7.
go back to reference Cox JD, Stetz 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: 1341-46. 10.1016/0360-3016(95)00060-C.CrossRefPubMed Cox JD, Stetz 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: 1341-46. 10.1016/0360-3016(95)00060-C.CrossRefPubMed
8.
go back to reference Rubin P, Constine LS, Fajardo LF, Phillips TL, Wasserman TH: Late Effects Working Group. Overview. Late Effects of Normal Tissues (LENT) scoring system. Int J Radiat Oncol Biol Phys. 1995, 30: 1041-42. 10.1016/0360-3016(95)00057-6.CrossRef Rubin P, Constine LS, Fajardo LF, Phillips TL, Wasserman TH: Late Effects Working Group. Overview. Late Effects of Normal Tissues (LENT) scoring system. Int J Radiat Oncol Biol Phys. 1995, 30: 1041-42. 10.1016/0360-3016(95)00057-6.CrossRef
9.
go back to reference Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer. 1981, 47: 207-14.CrossRefPubMed Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer. 1981, 47: 207-14.CrossRefPubMed
10.
go back to reference Dinges S, Budach V, Stuschke M, Budach W, Boehmer D, Schrader M, Jahnke K, Sack H: Chemo-radiotherapy for locally advanced head and neck cancer – long-term results of a phase II trial. Eur J Cancer. 1997, 33: 1152-55. 10.1016/S0959-8049(97)00099-3.CrossRefPubMed Dinges S, Budach V, Stuschke M, Budach W, Boehmer D, Schrader M, Jahnke K, Sack H: Chemo-radiotherapy for locally advanced head and neck cancer – long-term results of a phase II trial. Eur J Cancer. 1997, 33: 1152-55. 10.1016/S0959-8049(97)00099-3.CrossRefPubMed
11.
go back to reference Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958, 53: 457-81.CrossRef Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958, 53: 457-81.CrossRef
12.
go back to reference Wibault P, Bensmaine MA, de Forni M, Armand JP, Tellez Bernal E, Guillot T, Recondo G, Domenge C, Janot F, Borel C, Luboinski B, Eschwege F, Cvitkovic E: Intensive concomitant chemoradiotherapy in locally advanced unresectable squamous cell carcinoma of the head and neck: a phase II study of radiotherapy with cisplatin and 7-week continuous infusional fluorouracil. J Clin Oncol. 1996, 14: 1192-200.PubMed Wibault P, Bensmaine MA, de Forni M, Armand JP, Tellez Bernal E, Guillot T, Recondo G, Domenge C, Janot F, Borel C, Luboinski B, Eschwege F, Cvitkovic E: Intensive concomitant chemoradiotherapy in locally advanced unresectable squamous cell carcinoma of the head and neck: a phase II study of radiotherapy with cisplatin and 7-week continuous infusional fluorouracil. J Clin Oncol. 1996, 14: 1192-200.PubMed
13.
go back to reference Paccagnella A, Orlando A, Marchiori C, Zorat PL, Cavaniglia G, Sileni VC, Jirillo A, Tomio L, Fila G, Fede A, 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.CrossRefPubMed Paccagnella A, Orlando A, Marchiori C, Zorat PL, Cavaniglia G, Sileni VC, Jirillo A, Tomio L, Fila G, Fede A, 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.CrossRefPubMed
14.
go back to reference Brizel DM: Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma. Sem Radiat Oncol. 1998, 8: 237-46.CrossRef Brizel DM: Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma. Sem Radiat Oncol. 1998, 8: 237-46.CrossRef
15.
go back to reference Merlano M, Benasso M, Corvo R, Rosso R, Vitale V, Blengio F, Numico G, Margarino G, Bonelli L, Santi L: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst. 1996, 88: 583-89.CrossRefPubMed Merlano M, Benasso M, Corvo R, Rosso R, Vitale V, Blengio F, Numico G, Margarino G, Bonelli L, Santi L: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst. 1996, 88: 583-89.CrossRefPubMed
16.
go back to reference Fu KK, Phillips TL, Silverberg IJ, Jacobs C, Goffinet DR, Chun C, Friedman MA, Kohler M, McWhirter K, Carter SK: 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. 1987, 5: 1410-18.PubMed Fu KK, Phillips TL, Silverberg IJ, Jacobs C, Goffinet DR, Chun C, Friedman MA, Kohler M, McWhirter K, Carter SK: 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. 1987, 5: 1410-18.PubMed
17.
go back to reference Slootweg PJ, Hordijk GJ, Koole R: Autopsy findings in patients with head and neck squamous cell cancer and their therapeutic relevance. Eur J Cancer B Oral Oncol. 1996, 32B: 413-15. 10.1016/S0964-1955(96)00032-2.CrossRefPubMed Slootweg PJ, Hordijk GJ, Koole R: Autopsy findings in patients with head and neck squamous cell cancer and their therapeutic relevance. Eur J Cancer B Oral Oncol. 1996, 32B: 413-15. 10.1016/S0964-1955(96)00032-2.CrossRefPubMed
18.
go back to reference Adelstein DJ, Tan EH, Lavertu P: Treatment of head and neck cancer: the role of chemotherapy. Crit Rev Oncol Hematol. 1996, 24: 97-116.CrossRefPubMed Adelstein DJ, Tan EH, Lavertu P: Treatment of head and neck cancer: the role of chemotherapy. Crit Rev Oncol Hematol. 1996, 24: 97-116.CrossRefPubMed
19.
go back to reference Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, George SL, Huang AT, Prosnitz LR: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998, 338: 1798-804. 10.1056/NEJM199806183382503.CrossRefPubMed Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, George SL, Huang AT, Prosnitz LR: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998, 338: 1798-804. 10.1056/NEJM199806183382503.CrossRefPubMed
20.
go back to reference Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, Flentje M, Eckel HE, Mueller RP: Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simulaneous chemotherapy – results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001, 50 (5): 1161-71. 10.1016/S0360-3016(01)01544-9.CrossRefPubMed Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, Flentje M, Eckel HE, Mueller RP: Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simulaneous chemotherapy – results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001, 50 (5): 1161-71. 10.1016/S0360-3016(01)01544-9.CrossRefPubMed
21.
go back to reference Taylor SG, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994, 12: 385-95.PubMed Taylor SG, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994, 12: 385-95.PubMed
Metadata
Title
A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas
Authors
Reinhold Graf
Bert Hildebrandt
Wolfgang Tilly
Hanno Riess
Roland Felix
Volker Budach
Peter Wust
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-30

Other articles of this Issue 1/2006

BMC Cancer 1/2006 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine