Head and neck cancer - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the main H&N cancer page for current regimens.

Locally advanced disease, induction

No induction

Regimen

Study	Years 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 XRP6976F/2503)	2002-2007	Phase 2/3 (C)	1. PF 2. TPF	Did not meet 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 inferior OS

No treatment given prior to definitive therapy.

Subsequent treatment

• 2007BAI18B03: Surgery, then adjuvant RT
• TTCC XRP6976F/2503: Definitive cisplatin & RT
• GSTTC H&N07: Definitive cetuximab & RT or cisplatin, 5-FU, RT

References

1. 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 PubMed
2. 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 PubMed
   1. 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 PubMed
3. 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 PubMed NCT00095875
4. 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 PubMed NCT01542931
   1. 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 PubMed
5. TTCC XRP6976F/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 contains dosing details in manuscript PubMed NCT00261703
6. 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 contains dosing details in manuscript PubMed NCT01086826

Adjuvant therapy

Placebo

Regimen

Study	Years 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-NR in abstract	Phase 3 (C)	Afatinib	Did not meet primary endpoint of DFS

No active antineoplastic treatment.

Preceding treatment

• LUX-Head & Neck 2: Carboplatin & RT or Cisplatin & RT
• GORTEC 2010-02: Cisplatin & RT

References

1. 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 Jun 13. [Epub ahead of print] link to original article link to PMC article PubMed NCT01345669
2. 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

Recurrent or metastatic disease, subsequent lines of therapy

Best supportive care

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Machiels et al. 2011 (Hx-EGFr-202)	2006-2009	Phase 3 (C)	Zalutumumab	Might have inferior OS

No active antineoplastic treatment.

References

1. 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 PubMed NCT00382031