Head and neck cancer - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main head and neck cancer page for current regimens.

5 regimens on this page
5 variants on this page


Locally advanced disease, definitive therapy

Bleomycin, Methotrexate, Vinblastine/RT

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Merlano et al. 1988 1983-1986 Phase 3 (E-switch-ic) Bleomycin, MTX, Vinblastine, then RT Seems to have superior PFS

Chemotherapy

Supportive therapy

Radiotherapy

  • RT as follows:
    • Cycles 3, 5, 7: 200 cGy per fraction x 10 fractions

14-day cycle for 7 cycles

References

  1. Merlano M, Rosso R, Sertoli MR, Bonelli L, Margarino G, Grimaldi A, Benasso M, Gardin G, Corvó R, Scarpati D, Barbieri A, Pallestrini E, Castiglia G, Santelli A, Scasso F, Bottero G, Ciurlo E, Fracchia P, Moratti M, Santi L. Sequential versus alternating chemotherapy and radiotherapy in stage III-IV squamous cell carcinoma of the head and neck: a phase III study. J Clin Oncol. 1988 Apr;6(4):627-32. link to original article contains dosing details in manuscript PubMed

Cetuximab & RT

Cetuximab & RT: Cetuximab & Radiation Therapy

Regimen variant #1, conventional RT (6800 cGy)

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gebre-Medhin et al. 2020 (ARTSCAN III) 2013-2018 Phase 3 (E-switch-ooc) Cisplatin & RT Did not meet primary endpoint of OS
OS36: 78% vs 88%
(HR 1.63, 95% CI 0.93-2.86)

Targeted therapy

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once 1 week before radiation therapy begins; then 250 mg/m2 IV over 60 minutes once per week during course of radiation therapy

Supportive therapy

Radiotherapy

  • Concurrent radiation therapy to primary tumor and lymph node metastases: 200 cGy fractions x 34 fractions, once per day, 5 days per week (total dose: 6800 cGy)
  • Concurrent radiation therapy to elective neck volumes: 160 cGy fractions x 34 fractions, once per day, 5 days per week (total dose: 5440 cGy)

7-week course


Regimen variant #2, conventional RT (7000 cGy)

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bonner et al. 2006 (IMCL-9815) 1999-2002 Phase 3 (E-RT-esc) Radiation therapy Seems to have superior OS (secondary endpoint)
Median OS: 49 vs 29.3 mo
(HR 0.74, 95% CI 0.57-0.97)
Lefebvre et al. 2013 (TREMPLIN) 2006-2008 Randomized Phase 2 (E-switch-ooc) Cisplatin & RT Did not meet primary endpoint of LP at 3 months
Ghi et al. 2017 (GSTTC H&N07) 2008-2012 Non-randomized part of phase 2/3 RCT
Tao et al. 2018 (GORTEC 2007-01) 2008-01 to 2014-03 Phase 3 (C) Carboplatin, 5-FU, Cetuximab, RT Inferior PFS
Hitt et al. 2013 (TTCC-2007-01) 2008-07-15 to 2013-07-05 Phase 3 (E-switch-ooc) Cisplatin & RT Inconclusive whether non-inferior OS (primary endpoint)
Median OS: 42.9 vs 63.6 mo
(HR 1.11, 90% CI 0.89-1.38)

Preceding treatment

  • TREMPLIN: TPF induction x 3
  • GSTTC H&N07: TPF x 3 versus No induction

Targeted therapy

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once 1 week before radiation therapy begins, then 250 mg/m2 IV over 60 minutes once per week during course of radiation therapy
    • IMCL-9815: A test dose of 20 mg IV over 10 minutes, followed by 30 minutes of observation, was given prior to the first full dose

Supportive therapy

Radiotherapy

  • Concurrent radiation therapy, 200 cGy fractions x 35 fractions, once per day, 5 days per week (total dose: 7000 cGy)

7-week course


Regimen variant #3, twice-daily RT

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bonner et al. 2006 (IMCL-9815) 1999-2002 Phase 3 (E-RT-esc) Radiation therapy Seems to have superior OS (secondary endpoint)
Median OS: 49 vs 29.3 mo
(HR 0.74, 95% CI 0.57-0.97)

Superior LRC (primary endpoint)

Targeted therapy

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once 1 week before radiation therapy begins, then 250 mg/m2 IV over 60 minutes once per week during course of radiation therapy
    • A test dose of 20 mg IV over 10 minutes, followed by 30 minutes of observation, was given prior to the first full dose

Supportive therapy

Radiotherapy

  • Concurrent radiation therapy, 120 cGy fractions x 60 to 64 fractions, twice per day, 5 days per week (total dose: 72 to 7680 cGy)

6- to 6.5-week course


Regimen variant #4, concomitant boost

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bonner et al. 2006 (IMCL-9815) 1999-2002 Phase 3 (E-RT-esc) Radiation therapy Seems to have superior OS (secondary endpoint)
Median OS: 49 vs 29.3 mo
(HR 0.74, 95% CI 0.57-0.97)

Targeted therapy

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once 1 week before radiation therapy begins, then 250 mg/m2 IV over 60 minutes once per week during course of radiation therapy
    • A test dose of 20 mg IV over 10 minutes, followed by 30 minutes of observation, was given prior to the first full dose

Supportive therapy

Radiotherapy

  • Concurrent radiation therapy as follows:
    • First 3.6 weeks: 180 cGy fractions x 18 fractions (total dose: 3240 cGy), once per day, 5 days per week for 3.6 weeks
    • Last 2.4 weeks, morning dose: 180 cGy fractions x 12 fractions (total dose: 2160 cGy), given 5 days per week over 2.4 weeks
    • Last 2.4 weeks, afternoon dose: 150 cGy fractions x 12 fractions (total dose: 1800 cGy), given 5 days per week over 2.4 weeks
    • Total dose for concomitant boost regimen: 7200 cGy

6-week course

References

  1. IMCL-9815: Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. link to original article contains dosing details in manuscript PubMed NCT00004227
    1. HRQoL analysis: Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. link to original article contains partial protocol PubMed
    2. Update: Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. link to original article contains partial protocol PubMed
    3. Subgroup analysis: Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. link to original article link to PMC article PubMed
  2. TREMPLIN: Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C, Blot E, Rives M, Reyt E, Tourani JM, Geoffrois L, Peyrade F, Guichard F, Chevalier D, Babin E, Lang P, Janot F, Calais G, Garaud P, Bardet E. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013 Mar 1;31(7):853-9. Epub 2013 Jan 22. link to original article contains dosing details in manuscript PubMed NCT00169247
  3. GSTTC H&N07: Ghi MG, Paccagnella A, Ferrari D, Foa P, Alterio D, Codecà C, Nolè F, Verri E, Orecchia R, Morelli F, Parisi S, Mastromauro C, Mione CA, Rossetto C, Polsinelli M, Koussis H, Loreggian L, Bonetti A, Campostrini F, Azzarello G, D'Ambrosio C, Bertoni F, Casanova C, Emiliani E, Guaraldi M, Bunkheila F, Bidoli P, Niespolo RM, Gava A, Massa E, Frattegiani A, Valduga F, Pieri G, Cipani T, Da Corte D, Chiappa F, Rulli E; GSTTC. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer: a phase II-III trial. Ann Oncol. 2017 Sep 1;28(9):2206-2212. link to original article contains dosing details in manuscript PubMed NCT01086826
  4. GORTEC 2007-01: Tao Y, Auperin A, Sire C, Martin L, Khoury C, Maingon P, Bardet E, Kaminsky MC, Lapeyre M, Chatellier T, Alfonsi M, Pointreau Y, Jadaud E, Géry B, Zawadi A, Tourani JM, Laguerre B, Coutte A, Racadot S, Hasbini A, Malaurie E, Borel C, Meert N, Cornely A, Ollivier N, Casiraghi O, Sun XS, Bourhis J. Improved outcome by adding concurrent chemotherapy to cetuximab and radiotherapy for locally advanced head and neck carcinomas: results of the GORTEC 2007-01 phase III randomized trial. J Clin Oncol. 2018 Nov 1;36(31):3084-90. Epub 2018 Jun 7. link to original article contains dosing details in manuscript PubMed NCT00609284
  5. ARTSCAN III: Gebre-Medhin M, Brun E, Engström P, Haugen Cange H, Hammarstedt-Nordenvall L, Reizenstein J, Nyman J, Abel E, Friesland S, Sjödin H, Carlsson H, Söderkvist K, Thomasson M, Zackrisson B, Nilsson P. ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer. J Clin Oncol. 2021 Jan 1;39(1):38-47. Epub 2020 Oct 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01969877
  6. TTCC-2007-01: Hitt R, Mesía R, Lozano A, Iglesias Docampo L, Grau JJ, Taberna M, Rubió-Casadevall J, Martínez-Trufero J, Morillo EDB, García Girón C, Vázquez Estévez S, Cirauqui B, Cruz-Hernández JJ. Randomized phase 3 noninferiority trial of radiotherapy and cisplatin vs radiotherapy and cetuximab after docetaxel-cisplatin-fluorouracil induction chemotherapy in patients with locally advanced unresectable head and neck cancer. Oral Oncol. 2022 Nov;134:106087. Epub 2022 Sep 18. link to original article PubMed NCT00716391
  7. GORTEC 2017-01: NCT02999087

Radiation therapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gollin et al. 1972 1961-NR Phase 3 (C) 5-FU & RT Seems to have inferior OS1
Sanchíz et al. 1990 1978-1988 Phase 3 (E-de-esc) 1. 5-FU & RT Inferior OS
2. RT; twice-daily Inferior OS
Wolf et al. 1991 1985-NR Non-randomized part of phase 3 RCT
Taylor et al. 1994a 1986-1991 Non-randomized part of phase 3 RCT
Merlano et al. 1992 1987-1990 Phase 3 (C) CF & RT Inferior OS2
Browman et al. 1994 1987-1991 Phase 3 (C) 5-FU & RT Might have inferior OS
Wendt et al. 1998 1989-1993 Phase 3 (C) Cisplatin, 5-FU, LV, RT Inferior OS
Brizel et al. 1998 1990-1995 Phase 3 (C) CF & RT Might have inferior OS
Jeremic et al. 2000 1991-1993 Phase 3 (C) Cisplatin & RT Inferior OS
Adelstein et al. 2003 (Head and Neck Intergroup) 1992-1999 Phase 3 (C) 1. CF & RT Did not meet primary endpoint of OS
2. Cisplatin & RT Seems to have inferior OS
Ruo Redda et al. 2010 1992-1995 Phase 3 (C) Carboplatin & RT Did not meet primary endpoint of LRC
Forastiere et al. 2003 (RTOG 91-11) 1992-2000 Phase 3 (C) See link See link
Calais et al. 1999 (GORTEC 94-01) 1994-1997 Phase 3 (C) Carboplatin, 5-FU, RT Seems to have inferior OS
Huguenin et al. 2004 (SAKK 10/94) 1994-2000 Phase 3 (C) Cisplatin & RT Did not meet primary endpoint of TTF
Budach et al. 2005 (ARO 95-06) 1995-1999 Phase 3 (C) 5-FU, Mitomycin, RT Seems to have inferior OS
Grau et al. 2003 1996-1999 Phase 3 (C) Mitomycin & RT Did not meet primary endpoint of LRC
Bourhis et al. 2011 1996-2000 Phase 3 (C) CF & RT Did not meet primary endpoint of EFS
Lefebvre et al. 2009 (EORTC 24954) 1996-2004 Phase 3 (E-switch-ic) See link See link
Bensadoun et al. 2006 (FNCLCC 96003) 1997-2002 Phase 3 (C) CF & RT Seems to have inferior OS
Bonner et al. 2006 (IMCL-9815) 1999-2002 Phase 3 (C) Cetuximab & RT Seems to have inferior OS
Vermorken et al. 2007 (TAX 323) 1999-2002 Non-randomized part of phase 3 RCT
Pointreau et al. 2009 (GORTEC 2000-01) 2000-2005 Non-randomized part of phase 3 RCT
Bourhis et al. 2012 (GORTEC 99-02) 2000-2007 Phase 3 (C) 1. Carboplatin, 5-FU, RT Seems to have inferior PFS
2. Carboplatin, 5-FU, RT; accelerated concurrent RT Might have inferior PFS
Ghosh-Laskar et al. 2014 2000-2007 Phase 3 (C) 1. Cisplatin & RT Seems to have inferior LRC
2. RT; accelerated Not reported
Yi et al. 2017 2002-2012 Phase 3 (C) Cisplatin & RT Did not meet primary endpoint of OS
Patil et al. 2023a 2017-07 to 2021-05 Phase 2/3 (C) Docetaxel & RT Inferior DFS24

1Reported efficacy for Gollin et al. 1972 is based on the 1976 update, for oral lesions only.
2Reported efficacy in Merlano et al. 1992 is based on the 1995 update.
This is included for historical context and is unlikely to be further completed.

Preceding treatment

  • RTOG 91-11: CF x 3 versus no induction
  • Taylor et al. 1994a: CF induction x 7
  • GORTEC 2000-01: CF x 3 versus TPF induction x 3
  • Wolf et al. 1991: CF induction x 3
  • TAX 323: CF x 4 versus TPF induction x 4
  • EORTC 24954: CF induction x 4

Radiotherapy

References

  1. Gollin FF, Ansfield FJ, Brandenburg JH, Ramirez G, Vermund H. Combined therapy in advanced head and neck cancer: a randomized study. Am J Roentgenol Radium Ther Nucl Med. 1972 Jan;114(1):83-8. link to original article PubMed
    1. Update: Lo TC, Wiley AL Jr, Ansfield FJ, Brandenburg JH, Davis HL Jr, Gollin FF, Johnson RO, Ramirez G, Vermund H. Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study. AJR Am J Roentgenol. 1976 Feb;126(2):229-35. link to original article PubMed
  2. Vermund H, Kaalhus O, Winther F, Trausjø J, Thorud E, Harang R. Bleomycin and radiation therapy in squamous cell carcinoma of the upper aero-digestive tract: a phase III clinical trial. Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):1877-86. link to original article PubMed
  3. Sanchíz F, Millá A, Torner J, Bonet F, Artola N, Carreño L, Moya LM, Riera D, Ripol S, Cirera L. Single fraction per day versus two fractions per day versus radiochemotherapy in the treatment of head and neck cancer. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1347-50. link to original article PubMed
  4. Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE, Endicott JW, McClatchey K, Henderson WG; Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991 Jun 13;324(24):1685-90. link to original article contains dosing details in abstract PubMed
  5. Merlano M, Vitale V, Rosso R, Benasso M, Corvò R, Cavallari M, Sanguineti G, Bacigalupo A, Badellino F, Margarino G, Brema F, Pastorino G, Marziano C, Grimaldi A, Scasso F, Sperati G, Pallestrini E, Garaventa G, Accomando E, Cordone G, Comella G, Daponte A, Rubagotti A, Bruzzi P, Santi L. Treatment of advanced squamous-cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. N Engl J Med. 1992 Oct 15;327(16):1115-21. link to original article PubMed
    1. Update: Merlano M, Benasso M, Corvò 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 May 1;88(9):583-9. link to original article PubMed
  6. Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC, Witt TR, Griem KL, Hartsell WF, Kies MS, Mittal B, Rebischung JL, Coupez DJ, Desphieux JL, Bobin S, LePajolec C. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. link to original article contains dosing details in manuscript PubMed
  7. Browman GP, Cripps C, Hodson DI, Eapen L, Sathya J, Levine MN. Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol. 1994 Dec;12(12):2648-53. link to original article PubMed
  8. Wendt TG, Grabenbauer GG, Rödel CM, Thiel HJ, Aydin H, Rohloff R, Wustrow TP, Iro H, Popella C, Schalhorn A. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol. 1998 Apr;16(4):1318-24. link to original article PubMed
  9. 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 Jun 18;338(25):1798-804. link to original article PubMed
  10. GORTEC 94-01: Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Bertrand P. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999 Dec 15;91(24):2081-6. link to original article PubMed
    1. Update: Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. link to original article contains dosing details in manuscript PubMed
  11. Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L. 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. 2000 Apr;18(7):1458-64. link to original article PubMed
  12. Head and Neck Intergroup: Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. link to original article contains dosing details in manuscript PubMed
  13. Grau C, Prakash Agarwal J, Jabeen K, Rab Khan A, Abeyakoon S, Hadjieva T, Wahid I, Turkan S, Tatsuzaki H, Dinshaw KA, Overgaard J. Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial. Radiother Oncol. 2003 Apr;67(1):17-26. link to original article PubMed
  14. RTOG 91-11: Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. link to original article contains dosing details in manuscript PubMed NCT00002496
    1. Update: Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. link to original article contains partial protocol link to PMC article PubMed
  15. SAKK 10/94: Huguenin P, Beer KT, Allal A, Rufibach K, Friedli C, Davis JB, Pestalozzi B, Schmid S, Thöni A, Ozsahin M, Bernier J, Töpfer M, Kann R, Meier UR, Thum P, Bieri S, Notter M, Lombriser N, Glanzmann C. Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy. J Clin Oncol. 2004 Dec 1;22(23):4665-73. Epub 2004 Nov 8. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. link to original article PubMed NCT00002654
    1. Update: Ghadjar P, Simcock M, Studer G, Allal AS, Ozsahin M, Bernier J, Töpfer M, Zimmermann F, Betz M, Glanzmann C, Aebersold DM; Swiss Group for Clinical Cancer Research. 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 Feb 1;82(2):524-31. Epub 2011 Feb 16. link to original article PubMed
  16. ARO 95-06: 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 Feb 20;23(6):1125-35. link to original article PubMed
    1. Update: Budach V, Stromberger C, Poettgen C, Baumann M, Budach W, Grabenbauer G, Marnitz S, Olze H, Wernecke KD, Ghadjar P. Hyperfractionated accelerated radiation therapy (HART) of 7060 cGy with concurrent 5-FU/Mitomycin C is superior to HART of 7760 cGy alone in locally advanced head and neck cancer: long-term results of the ARO 95-06 randomized phase III trial. Int J Radiat Oncol Biol Phys. 2015 Apr 1;91(5):916-24. Epub 2015 Feb 7. link to original article PubMed
  17. FNCLCC 96003: Bensadoun RJ, Bénézery K, Dassonville O, Magné N, Poissonnet G, Ramaïoli A, Lemanski C, Bourdin S, Tortochaux J, Peyrade F, Marcy PY, Chamorey E, Vallicioni J, Seng H, Alzieu C, Géry B, Chauvel P, Schneider M, Santini J, Demard F, Calais G. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC). Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):983-94. Epub 2006 Jan 10. link to original article PubMed NCT00003627
  18. IMCL-9815: Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. link to original article contains dosing details in manuscript PubMed NCT00004227
    1. HRQoL analysis: Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. link to original article contains partial protocol PubMed
    2. Update: Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. link to original article contains partial protocol PubMed
    3. Subgroup analysis: Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. link to original article link to PMC article PubMed
  19. TAX 323: Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC; TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. link to original article contains dosing details in manuscript PubMed NCT00003888
    1. HRQoL analysis: van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. link to original article contains dosing details in manuscript link to PMC article PubMed
  20. EORTC 24954: Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; EORTC Head and Neck Cancer Cooperative Group; EORTC Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27. link to original article link to PMC article PubMed NCT00002839
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Recurrent or metastatic disease, first-line therapy

CABO

CABO: Cisplatin, Amithopterin (Methotrexate), Bleomycin, Oncovin (Vincristine)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Clavel et al. 1994 1984-1987 Phase 3 (E-esc) 1. CF Seems to have superior ORR
2. Cisplatin Superior ORR

Chemotherapy

21-day cycles

References

  1. Clavel M, Vermorken JB, Cognetti F, Cappelaere P, de Mulder PH, Schornagel JH, Tueni EA, Verweij J, Wildiers J, Clerico M, Dalesio O, Kirkpatrick A, Snow GB; EORTC Head and Neck Cancer Cooperative Group. Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck: a phase III study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol. 1994 Jul;5(6):521-6. link to original article contains dosing details in abstract PubMed

Cisplatin & Cetuximab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Burtness et al. 2005 (ECOG E5397) 1999-2001 Phase 3 (E-esc) Cisplatin Did not meet primary endpoint of PFS

Note: Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.

Chemotherapy

Targeted therapy

  • Cetuximab (Erbitux) as follows:
    • Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8, 15, 22
    • Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22

28-day cycles (see note)

References

  1. ECOG E5397: Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; ECOG. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005 Dec 1;23(34):8646-54. link to original article contains dosing details in manuscript PubMed NCT00003809
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