Head and neck cancer - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main H&N cancer page for regimens that include active anticancer treatment.
=Locally advanced disease, induction=
==No induction==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mazeron et al. 1992 	1982-1986 	Phase 3 (C) 	BMFP 	Did not meet endpoint of OS
Paccagnella et al. 1994 	1986-1990 	Phase 3 (C) 	PF 	Did not meet primary endpoint of OS
Hitt et al. 2013 (TTCC 2503) 	2002-2007 	Phase 2/3 (C)	1. PF2. TPF	Did not meet co-primary endpoints of PFS/TTF
Zhong et al. 2012 (2007BAI18B03)	2008-2010 	Phase 3 (C) 	TPF 	Did not meet primary endpoint of OS
Ghi et al. 2017 (GSTTC H&N07) 	2008-2012 	Phase 2/3 (C)	TPF 	Seems to have shorter OS (primary endpoint)Median OS: 31.7 vs 54.7 mo(HR 1.35, 95% CI 1.02-1.82)
No treatment given prior to definitive therapy.
====Subsequent treatment====
*2007BAI18B03: Surgery, then adjuvant RT
*TTCC 2503: Definitive cisplatin & RT
*GSTTC H&N07: Definitive cetuximab & RT or cisplatin, 5-FU, RT
===References===
# Mazeron JJ, Martin M, Brun B, Grimard L, Lelièvre G, Vergnes L, Haddad E, Feuilhade F, Piedbois P, Strunski W, Peynègre R, Pierquin B, Le Bourgeois JP. Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck. 1992 Mar-Apr;14(2):85-91. link to original article EuroPMC
# Paccagnella A, Orlando A, Marchiori C, Zorat PL, Cavaniglia G, Sileni VC, Jirillo A, Tomio L, Fila G, Fede A, Endrizzi L, Bari M, Sampognaro E, Balli M, Gava A, Pappagallo GL, Fiorention MV. 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 Feb 16;86(4):265-72. link to original article EuroPMC
## Update: Zorat PL, Paccagnella A, Cavaniglia G, Loreggian L, Gava A, Mione CA, Boldrin F, Marchiori C, Lunghi F, Fede A, Bordin A, Da Mosto MC, Sileni VC, Orlando A, Jirillo A, Tomio L, Pappagallo GL, Ghi MG. Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up. J Natl Cancer Inst. 2004 Nov 17;96(22):1714-7. link to original article EuroPMC
# PARADIGM: Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler JJ, Limaye S, Riley S, Posner M. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013 Mar;14(3):257-64. Epub 2013 Feb 13. link to original article does not contain dosing details in abstract EuroPMC NCT00095875
# 2007BAI18B03: Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr, Sun J, Zhu HG, Tu WY, Li J, Cai YL, Wang LZ, Fan XD, Wang ZH, Hu YJ, Ji T, Yang WJ, Ye WM, Li J, He Y, Wang YA, Xu LQ, Wang BS, Kies MS, Lee JJ, Myers JN, Zhang ZY. Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin Oncol. 2013 Feb 20;31(6):744-51. Epub 2012 Nov 5. link to original article link to PMC article EuroPMC NCT01542931
## Update: Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr, Hong CS, Sun J, Zhu HG, Tu WY, Li J, Cai YL, Yin QM, Wang LZ, Wang ZH, Hu YJ, Ji T, Yang WJ, Ye WM, Li J, He Y, Wang YA, Xu LQ, Zhuang Z, Lee JJ, Myers JN, Zhang ZY. Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma. Oncotarget. 2015 Jul 30;6(21):18707-14. link to original article link to PMC article EuroPMC
# TTCC 2503: Hitt R, Grau JJ, López-Pousa A, Berrocal A, García-Girón C, Irigoyen A, Sastre J, Martínez-Trufero J, Brandariz Castelo JA, Verger E, Cruz-Hernández JJ; Spanish Head and Neck Cancer Cooperative Group (TTCC). A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol. 2014 Jan;25(1):216-25. Epub 2013 Nov 19. link to original article EuroPMC NCT00261703
##Update: Hitt R, Iglesias L, López-Pousa A, Berrocal-Jaime A, Grau JJ, García-Girón C, Martínez-Trufero J, Guix M, Lambea-Sorrosal J, Del Barco-Morillo E, León-Vintró X, Cunquero-Tomas AJ, Baste N, Ocaña A, Cruz-Hernández JJ; the Spanish Head and Neck Cancer Cooperative Group (TTCC). Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial. Clin Transl Oncol. 2021 Apr;23(4):764-772. Epub 2020 Aug 14. link to original article EuroPMC
# 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 (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group. 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 EuroPMC NCT01086826
=Adjuvant therapy=
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Burtness et al. 2019 (LUX-Head & Neck 2)	2011-2016 	Phase 3 (C)	Afatinib 	Did not meet primary endpoint of DFS
Racadot et al. 2022 (GORTEC 2010-02) 	2011-12 to 2017-12 	Phase 3 (C)	Afatinib 	Did not meet primary endpoint of DFS
No active antineoplastic treatment.
====Preceding treatment====
*LUX-Head & Neck 2: Definitive Carboplatin & RT or Cisplatin & RT
*GORTEC 2010-02: Definitive Cisplatin & RT
===References===
# LUX-Head & Neck 2: Burtness B, Haddad R, Dinis J, Trigo J, Yokota T, de Souza Viana L, Romanov I, Vermorken J, Bourhis J, Tahara M, Martins Segalla JG, Psyrri A, Vasilevskaya I, Nangia CS, Chaves-Conde M, Kiyota N, Homma A, Holeckova P, Del Campo JM, Asarawala N, Nicolau UR, Rauch D, Even C, Wang B, Gibson N, Ehrnrooth E, Harrington K, Cohen EEW; LUX-Head & Neck 2 investigators. Afatinib vs placebo as adjuvant therapy after chemoradiotherapy in squamous cell carcinoma of the head and neck: a randomized clinical trial. JAMA Oncol. 2019 Aug 1;5(8):1170-1180. Epub 2019 Jun 13. link to original article link to PMC article EuroPMC NCT01345669
# GORTEC 2010-02: Racadot S, Thennevet I, Ouldbey Y, Kaminsky MC, Bosset M, Martin L, Tao Y, Sire C, de Raucourt D, Alfonsi M, Malaurie E, Tourani JM, Fournel P, Vauleon E, Modesto A, Rolland F, Metzger S, Pommier P, Chabaud S, Dussart S; GORTEC group. Afatinib maintenance therapy following post-operative radiochemotherapy in head and neck squamous cell carcinoma: Results from the phase III randomised double-blind placebo-controlled study BIB2992ORL (GORTEC 2010-02). Eur J Cancer. 2023 Jan;178:114-127. Epub 2022 Nov 9. link to original article EuroPMC NCT01427478
=Recurrent or metastatic disease, subsequent lines of therapy=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Machiels et al. 2011 (Hx-EGFr-202)	2006-2009 	Phase 3 (C)	Zalutumumab	Might have shorter OS (primary endpoint)Median OS: 5.2 vs 6.7 mo(HR 1.30, 97.06% CI 0.95-1.75)
No active antineoplastic treatment.
===References===
# Hx-EGFr-202: Machiels JP, Subramanian S, Ruzsa A, Repassy G, Lifirenko I, Flygare A, Sørensen P, Nielsen T, Lisby S, Clement PM. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol. 2011 Apr;12(4):333-43. Epub 2011 Mar 4. link to original article EuroPMC NCT00382031
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Category:Null regimens
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Category:Head and neck cancers