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. 2021 Dec 20;12(12):CD006386.
doi: 10.1002/14651858.CD006386.pub4.

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy

Ambika Parmar  1 , Michaelina Macluskey  2 , Niall Mc Goldrick  3 , David I Conway  4 , Anne-Marie Glenny  5 , Janet E Clarkson  6 , Helen V Worthington  7 , Kelvin Kw Chan  8
Affiliations

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy

Ambika Parmar et al. Cochrane Database Syst Rev. .

Abstract

Background: Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.

Objectives: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.

Search methods: An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.

Selection criteria: We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.

Data collection and analysis: For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary.

Main results: We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias. For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence). There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence). Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.

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Conflict of interest statement

Kelvin KW Chan: none Ambika Parmar: none Michaelina Macluskey: none Niall McGoldrick: I am a Director of the company Mouth Cancer Scotland Ltd (MCS Ltd), owned by the Scottish Charity Let's Talk About Mouth Cancer SC045100. MCS Ltd was set up to deliver the Global Oral Cancer Forum 2020 and received donations from the Henry Shein Cares Foundation and from the corporate giving arm of Bristol Myers Squibb. David I Conway: none Anne‐Marie Glenny: none. I am a Co‐ordinating Editor with Cochrane Oral Health. Janet E Clarkson: none. I am a Co‐ordinating Editor with Cochrane Oral Health. Helen V Worthington: none. I am an Editor and former Co‐ordinating Editor with Cochrane Oral Health.

Figures

1
1
2
2
Risk of bias summary: review authors' judgements about the risk of different types of bias for each included study.
3
3
1.1
1.1. Analysis
Comparison 1: Induction chemotherapy plus locoregional treatment (LRT) versus LRT alone, Outcome 1: Overall survival
1.2
1.2. Analysis
Comparison 1: Induction chemotherapy plus locoregional treatment (LRT) versus LRT alone, Outcome 2: Disease‐free survival
1.3
1.3. Analysis
Comparison 1: Induction chemotherapy plus locoregional treatment (LRT) versus LRT alone, Outcome 3: Disease‐free survival
1.4
1.4. Analysis
Comparison 1: Induction chemotherapy plus locoregional treatment (LRT) versus LRT alone, Outcome 4: Locoregional control
1.5
1.5. Analysis
Comparison 1: Induction chemotherapy plus locoregional treatment (LRT) versus LRT alone, Outcome 5: Recurrent disease ‐ locoregional
2.1
2.1. Analysis
Comparison 2: Surgery + adjuvant treatment A versus surgery + adjuvant treatment B, Outcome 1: Overall survival ‐ adjuvant chemotherapy vs. observation
2.2
2.2. Analysis
Comparison 2: Surgery + adjuvant treatment A versus surgery + adjuvant treatment B, Outcome 2: Overall survival ‐ adjuvant chemoradiotherapy vs radiotherapy
2.3
2.3. Analysis
Comparison 2: Surgery + adjuvant treatment A versus surgery + adjuvant treatment B, Outcome 3: Overall survival ‐ adjuvant chemotherapy + radiotherapy vs. adjuvant radiotherapy
2.4
2.4. Analysis
Comparison 2: Surgery + adjuvant treatment A versus surgery + adjuvant treatment B, Outcome 4: Disease‐free survival
2.5
2.5. Analysis
Comparison 2: Surgery + adjuvant treatment A versus surgery + adjuvant treatment B, Outcome 5: Locoregional recurrence
2.6
2.6. Analysis
Comparison 2: Surgery + adjuvant treatment A versus surgery + adjuvant treatment B, Outcome 6: Recurrent disease (overall)
3.1
3.1. Analysis
Comparison 3: Concurrent chemoradiotherapy versus radiotherapy alone (non‐resectable), Outcome 1: Overall survival ‐ concurrent chemoradiotherapy vs. radiotherapy
3.2
3.2. Analysis
Comparison 3: Concurrent chemoradiotherapy versus radiotherapy alone (non‐resectable), Outcome 2: Overall survival ‐ alternating chemotherapy + radiotherapy vs. radiotherapy
3.3
3.3. Analysis
Comparison 3: Concurrent chemoradiotherapy versus radiotherapy alone (non‐resectable), Outcome 3: Disease‐free survival
3.4
3.4. Analysis
Comparison 3: Concurrent chemoradiotherapy versus radiotherapy alone (non‐resectable), Outcome 4: Locoregional control
3.5
3.5. Analysis
Comparison 3: Concurrent chemoradiotherapy versus radiotherapy alone (non‐resectable), Outcome 5: Locoregional control
4.1
4.1. Analysis
Comparison 4: Chemotherapy A (± LRT) versus chemotherapy B (± LRT), Outcome 1: Overall survival
4.2
4.2. Analysis
Comparison 4: Chemotherapy A (± LRT) versus chemotherapy B (± LRT), Outcome 2: Disease‐free survival
4.3
4.3. Analysis
Comparison 4: Chemotherapy A (± LRT) versus chemotherapy B (± LRT), Outcome 3: Locoregional control
4.4
4.4. Analysis
Comparison 4: Chemotherapy A (± LRT) versus chemotherapy B (± LRT), Outcome 4: Overall survival
4.5
4.5. Analysis
Comparison 4: Chemotherapy A (± LRT) versus chemotherapy B (± LRT), Outcome 5: Locoregional control
See this image and copyright information in PMC

Update of

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Gupta 2009 {published data only}
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Paccagnella 1994 {published data only}
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Richard 1974 {published data only}
    1. Richard JM, Sancho H, Brugere J, Vandenbrouck C. Intra-arterial methotrexate in head and neck tumors. European Journal of Cancer 1973;9(11-12):847-51. - PubMed
    1. Richard JM, Sancho H, Lepintre Y, Rodary J, Pierquin B. Intra-arterial methotrexate chemotherapy and telecobalt therapy in cancer of the oral cavity and oropharynx. Cancer 1974;34(3):491-6. - PubMed
Richard 1991 {published data only}
    1. Richard J, Sancho GH. Intra-arterial infusion. An adjuvant to surgery of oral carcinoma. A randomized EORTC study. Journal Europeen de Radiotherapie 1983;4:81-6.
    1. Richard JM, Kramar A, Molinari R, Lefebvre JL, Blanchet F, Jortay A, et al. Randomised EORTC head and neck cooperative group trial of preoperative intra-arterial chemotherapy in oral cavity and oropharynx carcinoma. European Journal of Cancer 1991;27(7):821-7. - PubMed
Rischin 2005 {published data only}
    1. Rischin D, Peters L, Fisher R, Macann A, Denham J, Poulsen M, et al. 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). Journal of Clinical Oncology 2005;23(1):79-87. - PubMed
    1. Rischin D, Peters L, Smith J. Preliminary results of TROG 98.02 - a randomized phase II study of 5-fluorouracil, cisplatin and radiation versus tirapazamine, cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (abstract). Proceedings of the American Society of Clinical Oncology; 2003 2003;22:(abs no 1992).
Rischin 2010 {published data only}
    1. Rischin D, Peters LJ, O'Sullivan B, Giralt J, Fisher R, Yuen K, et al. Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): a phase III trial of the Trans-Tasman Radiation Oncology Group. Journal of Clinical Oncology 2010;28(18):2989-95. - PubMed
Ruo 2010 {published data only}
    1. Ruo Redda MG, Ragona R, Ricardi U, Beltramo G, Rampino M, Gabriele P, et al. Radiotherapy alone or with concomitant daily low-dose carboplatin in locally advanced, unresectable head and neck cancer: definitive results of a phase III study with a follow-up period of up to ten years. Tumori 2010;96(2):246-53. - PubMed
Sahoo 2017 {published data only}
    1. Sahoo TK, Samanta DR, Senapati SR, Parida K. A comparative study on weekly versus three weekly cisplatinum based chemoradiation in loally advanced head and neck cancers. Journal of Clinical and Diagnostic Research 2017;11(1):XC07-XC11. - PMC - PubMed
Salvajoli 1992 {published data only}
    1. Salvajoli JV, Morioka H, Trippe N, Kowalski LP. A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma. European Archives of Oto-Rhino-Laryngology 1992;249(4):211-5. - PubMed
Schuller 1988 {published data only}
    1. Schuller DE, Metch B, Stein DW, Mattox D, McCracken JD. Preoperative chemotherapy in advanced resectable head and neck cancer: final report of the Southwest Oncology Group. Laryngoscope 1988;98(11):1205-11. - PubMed
    1. Schuller DE, Stein DW, Metch B. Analysis of treatment failure patterns. A Southwest Oncology Group Study. Archives of Otolaryngology - Head & Neck Surgery 1989;115(7):834-6. - PubMed
Segura 2002 {published data only}
    1. Segura A, Pastor M, Santaballa A, Yuste A, Garcera S, Oltra A, et al. Cisplatin plus 5-fluorouracil vs cisplatin plus vinorelbine as neoadjuvant treatment in locally advanced head and neck cancer. Preliminary results of a randomized trial. European Journal of Cancer 1999;35(Suppl 2):S61.
    1. Segura A, Yuste A, Pastor M, Lopez-Tendero P, Perez-Fidalgo J, Girones R, et al. Cristalin-5-fluorouracilo versus cisplatin-vinorelbine in the treatment of locally advanced head and neck epidermoid carcinomas [Cisplatino-5 fluorouracilo versus cisplatino-vinorrelbina como tratamiento de los carcinomas epidermoid de cabeza y cuello localmente avanzados]. Oncologia 2002;25:466-71.
Shanta 1980 {published data only}
    1. Shanta V, Krishnamurthi S. Combined bleomycin and radiotherapy in oral cancer. Clinical Radiology 1980;31(5):617-20. - PubMed
    1. Shanta V, Krishnamurthi S. Combined therapy of oral cancer bleomycin and radiation: a clinical trial. Clinical Radiology 1977;28(4):427-9. - PubMed
Smid 1995 {published data only}
    1. Smid L, Lesnicar H, Zakotnik B, Soba E, Budihna M, Furlan L, et al. Radiotherapy, combined with simultaneous chemotherapy with mitomycin C and bleomycin for inoperable head and neck cancer - preliminary report. International Journal of Radiation Oncology, Biology, Physics 1995;32(3):769-75. - PubMed
    1. Zakotnik B, Budihna M, Smid L, Soba E, Zargi M. Concomitant radiotherapy and chemotherapy of inoperable head and neck squamous cell carcinomas. European Journal of Cancer 1993;Suppl 6:S226.
    1. Zakotnik B, Smid L, Budihna M, Lesnicar H, Soba E, Furlan L, et al. Concomitant radiotherapy and mitomycin C with bleomycin in inoperable head and neck cancer. Radiology and Oncology 1997;31:173-7.
    1. Zakotnik B, Smid L, Budihna M, Lesnicar H, Soba E, Furlan L, et al. Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report. International Journal of Radiation Oncology, Biology, Physics 1998;41(5):1121-7. - PubMed
    1. Zakotnik B, Smid L, Lesnicar H, Soba E, Budihna M, Furlan L, et al. Concomitant radiotherapy and mitomycin C with bleomycin in inoperable head and neck cancer. Annals of Oncology 1994;5(Suppl 8):121.
Staar 2001 {published data only}
    1. Semrau R, Mueller RP, Stuetzer H, Staar S, Schroeder U, Guntinas-Lichius O, et al. Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics 2006;64(5):1308-16. - PubMed
    1. Staar, S, Rudat, V, Dietz, A. Hyperfractionated (HF) accelerated (ACC) radiochemotherapy (RCT) versus HF/ACC radiotherapy (RT) in advanced head and neck (HN) cancer (abstract). In: ASCO; 2000. Vol. 19. 2000:411a.
    1. Staar S, Eckel HE, Rudat V, Dietz A, Flentje M, Schroeder M, et al. Benefits and toxicities of accelerated radiochemo- versus accelerated radiotherapy in advanced head and neck cancer - results of a German randomized study. European Journal of Cancer 2001;37(Suppl 6):38 (abs no 126).
    1. Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy - results of a multicentric randomized German trial in advanced head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics 2001;50(5):1161-71 [Erratum in International Journal of Radiation Oncology, Biology, Physics 2001; 51(2)1. - PubMed
    1. Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy - results of a multicentric randomized German trial in advanced head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics 2002;54:300. - PubMed
Szabo 1999 {published data only}
    1. Szabo G, Kreidler J, Hollmann K, Kovacs A, Nemeth G, Nemeth Z, et al. Intra-arterial preoperative cytostatic treatment versus preoperative irradiation: a prospective, randomized study of lingual and sublingual carcinomas. Cancer 1999;86(8):1381-6. - PubMed
Szpirglas 1979 {published data only}
    1. Szpirglas H, Chastang C, Bertrand JC. Adjuvant treatment of tongue and floor of the mouth cancers. Recent Results in Cancer Research 1978;68:309-17. - PubMed
    1. Szpirglas H, Chastang Cl, Bertrand JCh. Adjuvant treatment of tongue and floor of the mouth cancers. In: Bonadonna G, Mathé G, Salmon SE, editors(s). Adjuvant Therapies and Markers of Post-Surgical Minimal Residual Disease II. Adjuvant Therapies of the Various Primary Tumors. Berlin: Springer Verlag, 1979:309-17.
Szpirglas 1988 {published data only}
    1. Szpirglas H, Nizri D, Marneur M. Neoadjuvant chemotherapy. A randomized trial before radiotherapy in oral and oropharyngeal carcinomas: end results. In: 2nd International Head and Neck Oncology Research Conference; 1988. 1988:261-4.
Takasci‐Nagy 2015 {published data only}
    1. Takacsi-Nagy Z, Hitre E, Remenar E, Oberna F, Polgar C, Major T, et al. Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III–IV unresectable head and neck cancer. Strahlenther Onkol 2015;191:635-41. - PubMed
Tejedor 1992 {published data only}
    1. Tejedor M, Murias A, Soria P, Aguiar J, Salinas J, Hernandez MA, et al. Induction chemotherapy with carboplatin and ftorafur in advanced head and neck cancer. A randomized study. American Journal of Clinical Oncology 1992;15(5):417-21. - PubMed
Tousif 2020 {published data only}
    1. Tousif D, Sarathy V, Kumar R, Naik R. Randomized controlled study comparing efficacy and toxicity of weekly vs. 3-weekly induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Frontiers in Oncology 2020;10:1284. - PMC - PubMed
UKHAN 2010 {published and unpublished data}
    1. Monson K, Meadows H, Houghton J, Tobias JS. Combined modality treatment in head and neck cancer: an update on the UKHAN trial. Clinical Oncology 1996;8(5):340.
    1. Tobias J, Monson K, Gupta N, MacDougall H, Glaholm J, Peto J, et al. Does chemotherapy have a role in the management of patients with advanced head and neck cancer? Early results from the UK head and neck (UKHAN) trial (abstract). In: American Society of Clinical Oncology; 2001. Vol. 20. 2001:(abs no 888).
    1. Tobias JS, Monson K, Gupta N, Macdougall H, Glaholm J, Hutchison I, et al. Chemoradiotherapy for locally advanced head and neck cancer: 10-year follow-up of the UK Head and Neck (UKHAN1) trial. Lancet Oncology 2010;11(1):66-74. - PMC - PubMed
    1. Tobias JS, Monson KM, Glaholm J, MacDougall RH, Gupta NK, Peto J, et al. Early results from the UK head and neck (UKHAN) trial: the role of chemotherapy in primary management of advanced head and neck cancer. British Journal of Cancer 2001;85(Suppl 1):20.
    1. Tobias JS, Monson KM, Glaholm J, MacDougall RH, Gupta NK. UKHAN 1: a prospective multi-centre randomised trial investigating chemotherapy as part of initial management in advanced head and neck cancer. Radiotherapy and Oncology 2001;58(Suppl 1):S16.
Vermorken 2007 {published data only}
    1. Bernier J, Coens C, Remenar E, Van Herpen C, Germa Lluch J, Stewart S, et al. Impact on quality of life (QoL) of the addition of docetaxel (T) to neoadjuvant cisplatin plus 5-fluorouracil treatment in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN): EORTC study 24971. Journal of Clinical Oncology 2006;24(18S):5522.
    1. Biakhov M, Betka J, Shah P, Julka P. Results of a randomized phase 2 trial of docetaxel (TXT) with cisplatin (CDDP) or TXT with 5-fluorouracil (5FU) in patients (pts) with unresectable locally advanced squamous cell carcinoma of the head and neck (SCCHN). Annals of Oncology 2000;11(Suppl 4):92.
    1. Biakhov M, Shah P, Betka J, Doval D, Garin A. A randomized phase II trial of taxotere (TXT) with cisplatin (CDDP) or TXT with 5-fluorouracil (5FU) in patients (PTS) with unresectable locally advanced squamous cell carcinoma of the head and neck (abstract). In: American Society of Clinical Oncology; 2000. 2000:(abs no 1657).
    1. Remenar E, Van Herpen C, Germa Lluch J, Stewart S, Gorlia T, Degardin M, et al. A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971. Journal of Clinical Oncology 2006;24(18S):5516.
    1. Vermorken J, Remenar E, Van Herpen C, Germa Lluch J, Stewart S, Gorlia T, et al. Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): a phase III trial of the EORTC Head and Neck Cancer Group (EORTC #24971). Journal of Clinical Oncology 2004;22:14S (abs no 5508).
Vokes 1990 {published data only}
    1. Vokes EE, Panje WR, Mick R, Kozloff MF, Moran WJ, Sutton HG, et al. A randomized study comparing two regimens of neoadjuvant and adjuvant chemotherapy in multimodal therapy for locally advanced head and neck cancer. Cancer 1990;66(2):206-13. - PubMed
Volling 1999 {published data only}
    1. Schroder M, Muller RP, Knufermann H, Volling P. Improved survival after neoadjuvant carboplatin/5 FU in resectable stage II and III squamous cell carcinomas of the oral cavity and tonsil. European Journal of Cancer 1993;29Y:S144.
    1. Volling P, Ebeling O, Schroder M. Results of a prospective randomized trial with induction chemotherapy for cancer of the oral cavity and tonsil. European Archives of Oto-Rhino-Laryngology 1999;256(1):45. - PubMed
    1. Volling P, Schroder M, Eckel H, Ebeling O, Stennert E. Results of a prospective randomized trial with induction chemotherapy for cancer of the oral cavity and tonsils. Deutsche Gesellschaft der Hals- Nasen- und Ohrenärzte 1999;47(10):899-906. - PubMed
    1. Volling P, Schroder M, Muller RP, Ebeling O, Quirin R, Stennert E. Induction chemotherapy in primary resectable head and neck tumors: a prospective randomized trial. International Journal of Oncology 1994;4:909-14. - PubMed
    1. Volling P, Schroder M. Carboplatin/5-FU + operation + radiotherapy versus operation + radiotherapy by primary operable head and neck carcinomas: 4-year results. European Archives of Oto-Rhino-Laryngology 1993;Suppl II:175.
Weissler 1992 {published data only}
    1. Keegan P, Pillsbury H, Weissler M. Simultaneous cisplatinum -5FU and radiotherapy versus radiotherapy alone in advanced carcinoma of the head and neck. In: American Society of Clinical Oncology; 1988. Vol. 7. 1988:157.
    1. Weissler MC, Melin S, Sailer SL, Qaqish F, Rosenman JG, Pillsbury HC. Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Archives of Otolaryngology - Head & Neck Surgery 1992;118(8):806-10. - PubMed
Wendt 1998 {published data only}
    1. Wendt T, Grabenbauer GG, Thiel HJ. Simultaneous radiation therapy and chemotherapy versus radiation therapy alone in stage III and IV carcinoma of the head and neck: results of a randomized trial. In: 81st Scientific Assembly and Annual Meeting of the Radiological Society of North America; 1995. Vol. 197 Suppl. 1995.
    1. Wendt TG, Grabenbauer GG, Rodel CM, Thiel HJ, Aydin H, Rohloff R, et al. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. Journal of Clinical Oncology 1998;16(4):1318-24. - PubMed

References to studies excluded from this review

Abdel Wahab 2006 {published data only}
    1. Abdel Wahab MMA, Ezz Alarab LR, Adly A, El Fiky LM. Radiotherapy versus concurrent chemotherapy followed by adjuvant chemotherapy in the treatment of locally advanced head and neck cancer. Annals of Oncology 2006;17(9 Suppl 9):179-80.
Abele 1984 {published data only}
    1. Abele R, Honegger HP, Grossenbacher R, Kaplan E, et al. Randomized trial of methotrexate (M), bleomycin (B) hydroxyurea (HU) with versus without cisplatin in advanced squamous cell carcinoma of head and neck. In: Proceedings of the American Society of Clinical Oncology. 1984:186 (Abs No C724).
Abele 1985 {published data only}
    1. Abele R, Honegger HP, Wolfensberger M, Grossenbacher R, Mermillod B, Cavalli F. Methotrexate (M), bleomycin (B), hydroxyurea (HU) versus M+B+HU and cisplatin (C) in stage III-IV squamous cell carcinoma of the head and neck: a randomized study. Cancer Chemotherapy and Pharmacology 1985;14(Suppl 1):S1.
Addeo 2018 {published data only}
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Adelstein 1997 {published data only}
    1. Adelstein DJ, Saxton JP, Lavertu P, Tuason L, Wood BG, Wanamaker JR, et al. A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head & Neck 1997;19(7):567-75. - PubMed
Adelstein 2000 {published data only}
    1. Adelstein DJ, Lavertu P, Saxton JP, Secic M, Wood BG, Wanamaker JR, et al. Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 2000;88(4):876-83. - PubMed
Ahmad Khalil 2016 {published data only}
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Alam 2016 {published data only}
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Amichetti 1989 {published data only}
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Andreadis 1999 {published data only}
    1. Andreadis C, Sidiropoulos J, Vahtsevanos K, Thomaidis J. A phase III study of concurrent radiotherapy with carboplatin or weekly paclitaxel in patients with advanced squamous cell head and neck cancer (SCHNC). European Journal of Cancer 1999;35 Suppl 4:S172.
Anonymous 1976 {published data only}
    1. Anonymous. Bleomycin in advanced squamous cell carcinoma: a random controlled trial. Report of Medical Research Council Working Party on Bleomycin. BMJ 1976;1(6003):188-90. - PMC - PubMed
Ansfield 1970 {published data only}
    1. Ansfield FJ, Ramirez G, Davis HL Jr, Korbitz BC, Vermund H. Treatment of advanced cancer of the head and neck. Cancer 1970;25:78-82. - PubMed
Antanadou 2002 {published data only}
    1. Antonadou D, Pepelassi M, Synodinou M, Puglisi M, Throuvalas N. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics 2002;52(3):739-47. - PubMed
Argiris 2016 {published data only}
    1. Argiris A, Bauman JE, Ohr J, Gooding WE, Heron DE, Duvvuri U, et al. Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer. Annals of Oncology 2016;27(8):1594-600. - PMC - PubMed
Armstrong 2006 {published data only}
    1. Armstrong JG. Cetuximab plus radiotherapy for head and neck cancer. New England Journal of Medicine 2006;354(20):2187. - PubMed
Asif 2003 {published data only}
    1. Asif R, Chandra K, Chopra V, Bhatt. Concurrent cisplatin and radiotherapy in advanced head and neck cancer. Indian Journal of Otolaryngology and Head and Neck Surgery 2003;55(2):94-6. - PMC - PubMed
Auersperg 1977 {published data only}
    1. Auersperg M, Soba E, Vraspir PO. Intravenous chemotherapy with syndronization in advanced cancer of oral cavity and oropharynx. Zeitschrift fur Krebsforschung und Klinische Onkologie 1977;90:149-59. - PubMed
Autorino 2017 {published data only}
    1. Autorino R, Massaccesi M, Pesce A, Balducci M, Di Napoli N, Tartaglione T, et al. Low dose fractionated RT in association to TPF as induction therapy in advanced head and neck cancer. Radiotherapy and Oncology 2017;123:S599-600.
Babu 2010 {published data only}
    1. Babu KG, Viswanath L, Reddy BK, Shenoy K, Shenoy A, Naveen T, et al. An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): four-year survival results from a phase IIb study. Journal of Clinical Oncology 2010;28:Abstract 5530.
Bachaud 1996 {published data only}
    1. Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, ly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. International Journal of Radiation Oncology, Biology, Physics 1996;36(5):999-1004. - PubMed
    1. Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. International Journal of Radiation Oncology, Biology, Physics 1991;20(2):243-6. - PubMed
Bakowski 1978 {published data only}
    1. Bakowski MT, Macdonald E, Mould RF, Cawte P, Sloggem J, Barrett A, et al. Double blind controlled clinical trial of radiation plus razoxane (ICRF 159) versus radiation plus placebo in the treatment of head and neck cancer. International Journal of Radiation Oncology, Biology, Physics 1978;4(1-2):115-9. - PubMed
Baliga 2017 {published data only}
    1. Baliga S, Kabarriti R, Ohri N, Guha C, Kalnicki S, Garg M. The impact of radiotherapy, in addition to chemotherapy, on overall survival in the initial management of patients with newly diagnosed metastatic head and neck squamous cell carcinoma. Journal of Clinical Oncology 2017;15 Supplement 1:not identified.
Bari 2018 {published data only}
    1. Bari MA, Alam S, Sharmin S, Shamsunnahar, Uddin J, Alam N. Outcome of concurrent chemoradiotherapy and radiotherapy alone following induction chemotherapy in locally advanced squamous cell carcinoma of head and neck. Bangladesh Medical Research Council Bulletin 2018;44(2):93-7.
Barney 2017 {published data only}
    1. Barney C, Walston S, Zamora P, Nolan N, Diavolitsis V, Blakaj D, et al. Cetuximab versus platinum-based chemoradiation in locally advanced p16 positive oropharyngeal cancer. In: Annual Conference of the European Society for Radiotherapy and Oncology, ESTRO 36, 2017; Austria 123. 2017:S174-5.
Bell 2017 {published data only}
    1. Bell BR, Leidner R, Duhen R, Koguchi Y, Weinberg A. A phase IB neoadjuvant trial of anti-OX-40 (medi6469) prior to definitive surgical resection in patients with head and neck squamous cell carcinoma. In: 6th World Congress of the International Academy of Oral Oncology, IAOO, 2017; India. 39. 2017:E46-7.
Berger 1995 {published data only}
    1. Berger C, Chapet S, Calais G, Reynaud-Bougnoux A, Garand G, le FO. Concomitant radiochemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced carcinoma of the oropharynx. Results of a phase II trial. Bulletin du Cancer 1995;82(12):1044-51. - PubMed
Beryhy 2017 {published data only}
    1. Beryhy S. Acute toxicity profile of concomitant chemoradiotherapy in head and neck cancers: a randomized controlled comparison of weekly versus triweekly cisplatin schedule. Annals of Oncology 2017;29(Suppl 10):X102-3.
Bezwoda 1979 {published data only}
    1. Bezwoda WR, De Moor NG, Derman DP. Treatment of advanced head and neck cancer by means of radiation therapy plus chemotherapy - a randomised trial. Medical & Pediatric Oncology 1979;6(4):353-8. - PubMed
Bhattasali 2016 {published data only}
    1. Bhattasali O, Iganej S. Cetuximab-based bioradiation therapy versus cisplatin-based chemoradiation therapy in the definitive treatment of locally advanced oropharyngeal squamous cell carcinoma. In: International Journal of Radiation Oncology (58th Annual Meeting of the American Society for Radiation O, ASTRO). Vol. 96. 2016:S82-3.
Bier 1986 {published data only}
    1. Bier J. Prospective randomized clinical trial for squamous cell carcinomas of the oral cavity: preoperative chemotherapy versus postoperative chemotherapy versus surgery alone. Journal of Cancer Research & Clinical Oncology 1986;111:S121.
Boidi 1991 {published data only}
    1. Boidi TA, Rovea P, Gabriele AM, Tseroni V, Fracchia F, Raiteri M, et al. Simultaneous treatment with c-DPP and radiation therapy for advanced head and neck tumors. A randomized study. Radiologia Medica 1991;82(4):504-7. - PubMed
Bolla 1994 {published data only}
    1. Bolla M, Lefur R, Ton Van J, Domenge C, Badet JM, Koskas Y, et al. Prevention of second primary tumours with etretinate in squamous cell carcinoma of the oral cavity and oropharynx. Results of a multicentric double-blind randomised study. European Journal of Cancer 1994;30A:767-72. - PubMed
Bonner 2006 {published data only}
    1. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. New England Journal of Medicine 2006;354(6):567-78. - PubMed
Bouillet 2007 {published data only}
    1. Bouillet T, Nizri D, Zawadi A, Herman D, Cupissol D, Demaux H, et al. A randomized phase II study of concomitant CT (docetaxel [plus or minus] cisplatin) and (RT) in first-line treatment of locally advanced head and neck cancer (LAHNC). Journal of Clinical Oncology 2007;25(18S):6047. [DOI: 10.1200/jco.2007.25.18_suppl.6047] - DOI
Bradley 1982 {published data only}
    1. Bradley PJ, Stell PM, Dalby JA, Fraser G, Strickland P. Does the addition of chemotherapy to radiotherapy improve survival in advanced head and neck cancer. Clinical Otolaryngology 1982;7:284.
Brigham 1998 {published data only}
    1. Brigham BA, Fisher RJ, Stewart J, Fong T, Mead K. Role of folinic acid in methotrexate treatment of head and neck squamous cancers. In: Proceedings of the American Society of Clinical Oncology; 1998. 1998:(Abs No 1518).
Browman 1983 {published data only}
    1. Browman GP, Archibald SD, Young JE, Hryniuk WM, Russell R, Kiehl K, et al. Prospective randomized trial of one-hour sequential versus simultaneous methotrexate plus 5-fluorouracil in advanced and recurrent squamous cell head and neck cancer. Journal of Clinical Oncology 1983;1(12):787-92. - PubMed
    1. Browman GP, Levine MN, Russell R, Young JE, Archibald SD. Survival results from a phase III study of simultaneous versus 1-hour sequential methotrexate-5-fluorouracil chemotherapy in head and neck cancer. Head & Neck Surgery 1986;8(3):146-52. - PubMed
    1. Browman GP, Young JEM, Archibald SD, Kiehl K. Prospective randomised trial of 1-hour sequential versus simultaneous methotrexate (MTX) + 5 fluorouracil (5FU) in squamous cell carcinoma of the head and neck (SCHN). In: Proceedings of the American Society of Clinical Oncology; 1983. 1983:158 (Abs No C-616). - PubMed
Browman 1988 {published data only}
    1. Browman GP, Levine MN, Goodyear MD, Russell R, Archibald SD, Jackson BS, et al. Methotrexate/fluorouracil scheduling influences normal tissue toxicity but not antitumor effects in patients with squamous cell head and neck cancer: results from a randomized trial. Journal of Clinical Oncology 1988;6(6):963-8. - PubMed
Browman 1990 {published data only}
    1. Browman GP, Goodyear MD, Levine MN, Russell R, Archibald SD, Young JE. Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: a randomized placebo-controlled clinical trial. Journal of Clinical Oncology 1990;8(2):203-8. - PubMed
Buentzel 2006 {published data only}
    1. Buentzel J, Micke O, Adamietz IA, Monnier A, Glatzel M, De Vries A. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study. International Journal of Radiation Oncology, Biology, Physics 2006;64(3):684-91. - PubMed
    1. Buentzel J, Monier A, Ammon G, Schmitt N, Willich N, Hammershaimb L, et al. Phase III randomized double blind placebo controlled trial of carboplatin and radiation therapy ± amifostine in patients with head and neck cancer. In: Proceedings of the 43rd Annual Meeting of ASTRO; 2001. Vol. Suppl. 2001:85 (Abs No 151).
Buglione 2017 {published data only}
    1. Buglione M, Maddalo M, Corvo R, Pirtoli L, Paiar F, Lastrucci L, et al. Subgroup analysis according to human papillomavirus status and tumor site of a randomized phase II trial comparing cetuximab and cisplatin combined with radiation therapy for locally advanced head and neck cancer. International Journal of Radiation Oncology Biology Physics 2017;97(3):462-72. - PubMed
Buntzel 1998 {published data only}
    1. Buntzel J, Glatzel M, Kuttner K, Weinaug R, Frohlich D. Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer. Seminars in Radiation Oncology 2002;12(1 Suppl 1):4-13. - PubMed
    1. Buntzel J, Schuth J, Kuttner K, Glatzel M. Radiochemotherapy with amifostine cytoprotection for head and neck cancer. Supportive Care in Cancer 1998;6(2):155-60. - PubMed
Buntzel 1998a {published data only}
    1. Buntzel J, Glatzel M, Schuth J, Weinaug R, Kuttner K, Frohlich D. Clinical experiences with amifostine in the radiochemotherapy of head neck cancer. Journal of Cancer Research & Clinical Oncology 1998;124 Suppl 1:R113.
    1. Buntzel J, Kuttner K, Frohlich D, Glatzel M. Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer. Annals of Oncology 1998;9(5):505-9. - PubMed
    1. Buntzel J, Schuth J, Weinaug R, Glatzel M, Frohlich D, Kuttner K. Cytoprotection with amifostine (A) as the base for intensification of radiochemotherapy in head and neck cancer. Annals of Hematology 1998;77 Suppl 2:S197.
Burtness 2017 {published data only}
    1. Burtness B, Haddad RI, Dinis J, Perez JMT, Yokota T, Viana LD, et al. LUX-head and neck 2: randomized, double-blind, placebo-controlled, phase III trial of afatinib as adjuvant therapy after chemoradiation (CRT) in primary unresected, high/intermediate-risk, squamous cell cancer of the head and neck (HNSCC) patients (pts). Journal of Clinical Oncology 2017;35:6001.
Campbell 1987 {published data only}
    1. Campbell JB, Dorman EB, McCormick M, Miles J, Morton RP, Rugman F, et al. A randomized phase III trial of cisplatinum, methotrexate, cisplatinum + methotrexate, and cisplatinum + 5-fluoro-uracil in end-stage head and neck cancer. Acta Oto-Laryngologica 1987;103(5-6):519-28. - PubMed
Caponigro 2002 {published data only}
    1. Caponigro F, De Rosa P, Rosati G, Avallons A, De Lucia L, Morrica B, et al. A phase 2 randomised study of cisplatin (CDDP) raltitrexed (TOM) levofolinic acid (LFA) and 5-fluoruracil (5-FU) or CDDP, methotrexate (MTX) LFA and 5-FU in locally advanced (LAD) or metastatic (M) head and neck cancer (HNC). Head and Neck Cancer 2001;37:S105-6.
    1. Caponigro F, Rosati G, De Rosa P, Avallone A, De Rosa V, De Lucia L, et al. Cisplatin, raltitrexed, levofolinic acid and 5-fluorouracil in locally advanced or metastatic squamous cell carcinoma of the head and neck: a phase II randomized study. Oncology 2002;63(3):232-8. - PubMed
Cappelaere 1981 {published data only}
    1. Cappelaere P, Chauvergne J, Klein T, Gary-Bobo J, Guerrin J, Meeus L. Randomized trial of vincristin-methotrexate-bleomycin and cis-platin or detorubicin for advanced head and neck cancer (author's transl). Bulletin du Cancer 1981;68(5):422-7. - PubMed
Cappelaere 1990 {published data only}
    1. Cappelaere P, Vignoud J, Fargeot P, Metz R, Chauvergne J, Meeus L, et al. Palliative chemotherapy of epidermoid carcinoma of the upper respiratory and digestive tracts with a combination of carboplatin and 5-fluorouracil. Bulletin du Cancer 1990;77(11):1099-105. - PubMed
Caroline 2016 {published data only}
    1. Caroline B, Sundus Y, Dawn D, Carol G, Susan M. Cost analysis of cetuximab (Erbitux) plus radiotherapy (ERT) versus concomitant cisplatin plus radiotherapy (CRT) within an NHS oncology unit (single institution): a pilot study. British Journal of Radiology 2016;89(1068):20160105. - PMC - PubMed
Carugati 1988 {published data only}
    1. Carugati A, Pradier R, De la Torre A. Combination chemotherapy preradical treatment for head and neck squamous cell carcinoma. In: Proceedings of the American Society of Clinical Oncology. Vol. 7. 1988:152.
Chang 2017 {published data only}
    1. Chang CL, Yuan KSP, Wu SY. High-dose or low-dose cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer. Head and Neck 2017;39(7):1364-70. - PubMed
Cheng 2017 {published data only}
    1. Cheng D, Pak K, Wei LJ. Demonstrating noninferiority of accelerated radiotherapy with panitumumab vs standard radiotherapy with cisplatin in locoregionally advanced squamous cell head and neck carcinoma. JAMA Oncology 2017;3(10):1430-1. - PMC - PubMed
Clavel 1987 {published data only}
    1. Clavel M, Cognetti F, Dodion P, Wildiers J, Rosso R, Rossi A, et al. Combination chemotherapy with methotrexate, bleomycin, and vincristine with or without cisplatin in advanced squamous cell carcinoma of the head and neck. Cancer 1987;60(6):1173-7. - PubMed
    1. Clavel M, Dodion P, Cognetti F, Van Rymenant M, Wildiers J, Rossi A, et al. Randomized trial of cisplatin (C), methotrexate (A), bleomycin (B) and vincristine (O) vs ABO in advanced squamous cell cancer of the head and neck. Cancer Chemotherapy and Pharmacology 1985;14 Suppl 1:S14. - PubMed
Coates 1984 {published data only}
    1. Coates AS, Tattersall MH, Swanson C, Hedley D, Fox RM, Raghavan D. Combination therapy with methotrexate and 5-fluorouracil: a prospective randomized clinical trial of order of administration. Journal of Clinical Oncology 1984;2(7):756-61. - PubMed
Cohen 2016 {published data only}
    1. Cohen E, Saba NF, Gitilitz B, Haddad R, Sukari A, Neupane P, et al. Active8: a randomized, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with motolimod immunotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Annals of Oncology 2016;27:LBA37.
Coninx 1986 {published data only}
    1. Coninx P, Nasca S, Jezekova D, Marechal F, Garbe E, Legros M, et al. Sequential trials in initial chemotherapy of advanced tumors of the upper aero-digestive system. Cis-diamminedichloroplatinum (DDP) versus DDP-etoposide (VP16). Bulletin du Cancer 1986;73(1):85-8. - PubMed
Coninx 1988 {published data only}
    1. Coninx P, Nasca S, Lebrun D, Panis X, Lucas P, Garbe E, et al. Sequential trial of initial chemotherapy for advanced cancer of the head and neck. DDP versus DDP + 5-fluorouracil. Cancer 1988;62(9):1888-92. - PubMed
Corvo 1997 {published data only}
    1. Corvo R, Giaretti W, Sanguineti G, Geido E, Bacigalupo A, Orecchia R, et al. Chemoradiotherapy as an alternative to radiotherapy alone in fast proliferating head and neck squamous cell carcinomas. Clinical Cancer Research 1997;3(11):1993-7. - PubMed
Cruz 1997 {published data only}
    1. Cruz JJ, Fonseca E, Rodriguez CA, Gomez A, Martin G, Sanchez P, et al. Randomized trial of cisplatin (P) plus 5-fluorouracil (F) with or without folinic acid in locally advanced head and neck cancer (LAHNC). European Journal of Cancer 1997;33:854. - PubMed
Cummings 2007 {published data only}
    1. Cummings B, Keane T, Pintilie M, Warde P, Waldron J, Payne D, et al. Five year results of a randomized trial comparing hyperfractionated to conventional radiotherapy over four weeks in locally advanced head and neck cancer. Radiotherapy and Oncology 2007;85(1):7-16. - PubMed
Dalley 1995 {published data only}
    1. Dalley D, Beller E, Aroney R, Dewar J, Page J, Philip R, et al. The value of chemotherapy (CT) prior to definitive local therapy (DLT) in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck (HN). In: Proceedings of American Society of Clinical Oncology. Vol. 14. 1995:297.
DeConti 1981 {published data only}
    1. DeConti RC, Schoenfeld D. A randomized prospective comparison of intermittent methotrexate, methotrexate with leucovorin, and a methotrexate combination in head and neck cancer. Cancer 1981;48(5):1061-72. - PubMed
Deka 1983 {published data only}
    1. Deka AC, Deka BC, Kalghatgi RR, Patil RB. Combination treatment in moderately advanced head & neck cancer. Indian Journal of Medical Research 1983;78 Suppl:74-80. - PubMed
De la Torre 1991 {published data only}
    1. De la Torre A, Aragon G, Valcarcel F, Magallon R, Cardenes H, Vazquez G, et al. A randomized study of radiotherapy treatment of advanced head and neck cancer, with vs without tegafur. European Journal of Cancer 1991;27 Suppl 2:S143.
Di Blasio 1994 {published data only}
    1. Di Blasio B, Barbieri W, Bozzetti A, Iotti C, Di Sarra S, Cocconi G. A prospective randomized trial in resectable head and neck carcinoma: loco-regional treatment with and without neoadjuvant chemotherapy. In: Proceedings of the American Society of Clinical Oncology. Vol. 13. 1994:279.
Dobrowsky 1996 {published data only}
    1. Dobrowsky W, Dobrowsky E, Naude J, Millesi W, Pavelka R, Kautzky M, et al. Conventional vs accelerated fractionation in head and neck cancer. British Journal of Cancer 1996;27:S279-81. - PMC - PubMed
Domenge 1987 {published data only}
    1. Domenge C, Marands P, Douillard JY, Peuvrel P, Prevost B, Lefebvre J, et al. Post surgical adjuvant chemotherapy in extracapsular spread invaded lymph node (N+ R+) of epidermoid carcinoma of the head and neck. A randomized multicentric trial. In: Proceedings of the European Conference on Clinical Oncology; 1987. Vol. 4. 1987:242.
Domenge 1988 {published data only}
    1. Domenge C, Marandas P, Vignoud J, et al. Post-surgical adjuvant chemotherapy in extracapsular spread invaded lymph node (N+R+) of epidermoid carcinoma of the head and neck: a randomized multicentric trial. In: 2nd International Conference on Head and Neck Cancer; 1988; Boston; American Society of Head & Neck Surgery. Vol. 74. 1988.
Drelichman 1983 {published data only}
    1. Drelichman A, Cummings G, al Sarraf M. A randomized trial of the combination of cis-platinum, oncovin and bleomycin (COB) versus methotrexate in patients with advanced squamous cell carcinoma of the head and neck. Cancer 1983;52(3):399-403. - PubMed
Driessen 2016 {published data only}
    1. Driessen C, Snik A, Leijendeckers J, De Boer JP, Gelderblom H, Van Opstal C, et al. Ototoxicity in locally advanced head and neck cancer (LAHNC) patients (pts) treated with induction chemotherapy (IC) followed by cisplatin-based chemoradiotherapy (CRT). Annals of Oncology 2016;27:989P.
Dutta 2013 {published data only}
    1. Dutta S, Ghorai S, Choudhury KB, Majumder A. Radical treatment of locally advanced head and neck cancer with concurrent chemo radiation-cisplatin versus carboplatin: a randomized comparative phase III trial. Clinical Cancer Investigation Journal 2013;2(2):122-7.
Ebeling 1994 {published data only}
    1. Ebeling O, Eckel HE, Volling P, Heitmann K, Vossing M. Cisplatin/5FU versus carboplatin/5FU. 5 year follow up. Head and Neck Oncology 1994;42(10):629-35. - PubMed
Eriksen 2013 {published data only}
    1. Eriksen JG, Maare C, Johansen J, Primdahl H, Evensen J, Kristensen CA, et al. DAHANCA 19: first results of a randomized phase III study of the importance of the EGFR-inhibitor zalutumumab for the outcome of primary curative radiotherapy for squamous cell carcinoma of the head and neck. European Journal of Cancer (European Cancer Congress, ECC, 27 Sept-1 Oct 2013; Amsterdam Netherlands) 2013;49:S6.
    1. Eriksen JG, Maare C, Johansen J, Primdahl H, Evensen JF, Kristensen CA, et al. Evaluation of the EGFR-Inhibitor zalutumumab given with primary curative (CHEMO) radiation therapy to patients with squamous cell carcinoma of the head and neck: results of the DAHANCA 19 randomized phase 3 trial. International Journal of Radiation Oncology, Biology, Physics 2014;88(2):465.
Eschwege 1997 {published data only}
    1. Chassagne D, Charreau I, Sancho-Garnier H, Eschwege F, Malaise EP. First analysis of tumor regression for the European randomized trial of etanidazole combined with radiotherapy in head and neck carcinomas. International Journal of Radiation Oncology, Biology, Physics 1992;22(3):581-4. - PubMed
    1. Eschwege F, Sancho-Garnier H, Chassagne D, Brisgand D, Guerra M, Malaise EP, et al. Results of a European randomized trial of etanidazole combined with radiotherapy in head and neck carcinomas. International Journal of Radiation Oncology, Biology, Physics 1997;39(2):275-81. - PubMed
Ezzat 2005 {published data only}
    1. Ezzat M, Shouman T, Zaza K, Safwat A, El-Khoudary A, El-Senosi M, et al. A randomized study of accelerated fractionation radiotherapy with and without mitomycin C in the treatment of locally advanced head and neck cancer. Journal of the Egyptian National Cancer Institute 2005;17(2):85-92. - PubMed
Fayette 2016 {published data only}
    1. Fayette J, Wirth L, Oprean C, Udrea A, Jimeno A, Rischin D, et al. Randomized phase II study of duligotuzumab (MEHD7945A) vs. cetuximab in squamous cell carcinoma of the head and neck (MEHGAN Study). Frontiers in Oncology 2016;6(OCT):232. - PMC - PubMed
Feng 2018 {published data only}
    1. Feng L, Qi S, Lin M. Efficacy and survival rate of intensity-modulated radiotherapy combined with chemotherapy for elderly patients with locally advanced oropharyngeal cancer. Experimental and Therapeutic Medicine 2018;15(3):2475-9. - PMC - PubMed
Ferris 2018 {published data only}
    1. Ferris RL, Blumenschein GR, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Two-year update from CheckMate 141: outcomes with nivolumab (NIVO) vs investigator's choice (IC) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the overall population and PD-l1 subgroups. International Journal of Radiation Oncology, Biology and Physics 2018;100(5):1317.
    1. Simpson S, Cocks K, Contente M, DeRosa M, Taylor F, Shaw JW. A quality-adjusted time without symptoms of disease and toxicity (Q-TWIST) analysis comparing nivolumab and therapy of investigator's choice (IC) in patients with recurrent or metastatic (R/M) platinum-refractory squamous cell carcinoma of the head and neck (SCCHN) (checkmate 141). In: ISPOR 20th Annual European Congress; 2017; United Kingdom: 20. Vol. 9. 2017:A450.
Fety 1994 {published data only}
    1. Fety R, Rolland F, Barberi-Heyob M, Merlin JL, Conroy T, Hardouin A, et al. Clinical randomized study of 5FU monitoring versus standard dose in patients with head and neck cancer: preliminary results. Anticancer Research 1994;14(6A):2347-52. - PubMed
Fety 1998 {published data only}
    1. Fety R, Rolland F, Barberi-Heyob M, Hardouin A, Campion L, Conroy T, et al. Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas. Clinical Cancer Research 1998;4(9):2039-45. - PubMed
Fonseca 1997 {published data only}
    1. Fonseca E, Cruz JJ, Rodriguez CA, Gomez-Bernal A, Martin G, Sanchez P, et al. Randomized trial of neoadjuvant chemotherapy with cisplatin plus 5-fluorouracil, with or without leucovorin, in locally advanced head and neck cancer. Annals of Oncology 1997;8(7):713-4. - PubMed
Fonseca 2005 {published data only}
    1. Cruz JJ, Fonseca E, Gomez JG, Rueda A. Randomized phase II trial of induction chemotherapy in patients with locally advanced head and neck carcinoma (LA-HNC) Docetaxel plus cisplatin (DP) versus cisplatin plus 5-FU (PF): interim results. In: Proceedings of the American Society of Clinical Oncology. 2002:(Abs No 920).
    1. Fonseca E, Grau JJ, Sastre J, Garcia-Gomez JM, Rueda A, Pastor M, et al. Induction chemotherapy with cisplatin/docetaxel versus cisplatin/5-fluorouracil for locally advanced squamous cell carcinoma of the head and neck: a randomised phase II study. European Journal of Cancer 2005;41(9):1254-60. - PubMed
Forastiere 2001 {published data only}
    1. Forastiere AA, Leong T, Rowinsky E, Murphy BA, Vlock DR, DeConti RC, et al. Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393. Journal of Clinical Oncology 2001;19(4):1088-95. - PubMed
Fountzalis 2004 {published data only}
    1. Fountzilas, G, Ciuleanu E, Theophanopoulou M, Kalogera-Fountzila A. A randomised study of concomitant radiotherapy with cisplatin or carboplatin versus radiotherapy alone in patients with locally advanced non-nasopharyngeal head and neck cancer. A Hellenic Cooperative Oncology group phase III study. In: Proceedings of the American Society of Clinical Oncology. 2003:495 (Abs No 1991).
    1. Fountzilas G, Ciuleanu E, Dafni U, Plataniotis G, Kalogera-Fountzila A, Samantas E, et al. Concomitant radiochemotherapy vs radiotherapy alone in patients with head and neck cancer. Medical Oncology 2004;21(2):95-107. - PubMed
Fu 1987 {published data only}
    1. Fu KK, Phillips TL, Silverberg IJ, Friedman MA. Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced head and neck cancer: interim report of NCOG randomized trial. In: Proceedings of the American Society of Clinical Oncology. 1983:159 (Abs No C-622). - PubMed
    1. Fu KK, Phillips TL, Silverberg IJ, Jacobs C, Goffinet DR, Chun C, et al. Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial. Journal of Clinical Oncology 1987;5(9):1410-8. - PubMed
Fujii 1996 {published data only}
    1. Fujii M, Ohno Y, Tokumaru Y, Imanishi Y, Kanke M. Combination chemotherapy with 5-FU and CDDP or CDDP analog for head and neck cancer. Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy] 1996;23(13):1740-6. - PubMed
Fujii 1999 {published data only}
    1. Fujii M, Kanke M, Tomita T. Low-dose CDDP and 5-FU for head and neck cancer patients. Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy] 1999;26(11):1542-7. - PubMed
Furukawa 1994 {published data only}
    1. Furukawa S, Tsukuda M, Mochimatsu I, Kokatsu T, Satoh H, Sakumoto M. Modified combination chemotherapy of cisplatin and 5-fluorouracil in squamous cell carcinomas of the head and neck. Auris, Nasus, Larynx 1994;21(3):181-5. - PubMed
Gabriele 1994 {published data only (unpublished sought but not used)}
    1. Gabriele P, Orrechia R, Ragona R, Airoldi M, Ciambellotti E. A cooperative AIRO/PIEMONTE randomized clinical trial of carboplatin as an adjunct to radiotherapy in head and neck cancer. Radiotherapy and Oncology 1994;32 Suppl 1:S93.
Gabriele 1996 {published data only}
    1. Gabriele P, Gandolfo S, Solazzo L, Gallesio C, Ragona R, Beltramo G, et al. A phase III study of radiotherapy alone versus radiotherapy plus carboplatin in stage III-IV head and neck cancers. An analysis on oral cavity cancer. Journal of Cranio Maxillo Facial Surgery 1996;24 Suppl 1:18.
Gaffor 2016 {published data only}
    1. Gaffor HA, Ruzina F, Sridhar CH. Advanced head and neck ca-chemoradiotherapy with conventional fraction and accelerated fraction. Radiotherapy and Oncology 2016;119:S519-20.
Gasparini 1992 {published data only}
    1. Gasparini G, Recher G, Testolin A, Dal FS, Panizzoni GA, Cristoferi V, et al. Synchronous radiotherapy and chemotherapy with cisplatin in the management of locally advanced or recurrent head and neck cancer. American Journal of Clinical Oncology: Cancer Clinical Trials 1992;15(3):242-9. - PubMed
Gedouin 1986 {published data only}
    1. Gedouin D, Desprez P, Perron JJ, Fleury F, Leclech G, Miglianico L, et al. Cancers of the base of the tongue and hypopharynx: results of a multicenter randomized trial of chemotherapy prior to locoregional treatment. Bulletin du Cancer Radiotherapie 1986;83(2):104-7. - PubMed
Gedouin 1996 {published data only}
    1. Gedouin D, Desprez P, Perron JJ, Fleury F, Leclech G, Miglianico L, et al. Cancers of the base of the tongue and hypopharynx: results of a multicenter randomized trial of chemotherapy prior to locoregional treatment. Bulletin du Cancer Radiotherapie 1996;83(2):104-7. - PubMed
Gehanno 1992 {published data only}
    1. Gehanno P, Depondt J, Peynegre R, Peytral C, Martin M, Baillet F, et al. Neoadjuvant combination of carboplatin and 5-FU in head and neck cancer: a randomized study. Annals of Oncology 1992;3 Suppl 3:43-6. - PubMed
Ghadjar 2014 {published data only}
    1. Ghadjar P, Hayoz S, Zimmermann F, Bodis S, Kaul D, Bernier J, et al. Impact of weight loss on survival after chemoradiation for locally advanced head and neck cancer: secondary results of a randomized phase 3 trial (SAKK 10/94). International Journal of Radiation Oncology, Biology and Physics 2014;90(1):S510-1. - PMC - PubMed
    1. Ghadjar P, Pottgen C, Joos D, Hayoz S, Baumann M, Bodis S, et al. Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers: secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10/94). Strahlentherapie und Onkologie 2016;192(8):552-60. - PubMed
Ghali 2011 {published data only}
    1. Ghali RR, El-Sharawy E, Adel AM, Ibrahim SA. Induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomittant chemoradiotherapy versus concomittant chemoradiotherapy in unresectable locally advanced head and neck cancer: a phase III randomized study. Medical Journal of Cairo University 2011;79(2):13-18.
Ghosh 2006 {published data only}
    1. Ghosh S, Agarwal JP, Bhutani R, Vora A, Prabhash K, D'Cruz A, et al. Randomized trial of conventional fractionated RT (CFRT) vs. concomitant chemo radiotherapy (CTRT) and accelerated radiotherapy (ACRT) in patients with advanced, non nasopharyngeal, squamous cell cancers of the head and neck region. International Journal of Radiation Oncology, Biology, Physics 2006;66(3 Suppl 1):S191.
Gibson 2005 {published data only}
    1. Gibson MK, Li Y, Murphy B, Hussain MHA, DeConti RC, Ensley J, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. Journal of Clinical Oncology 2005;23(15):3562-7. - PubMed
Gillison 2017 {published data only}
    1. Gillison ML, Ferris RL, Zhang Q, Colevas AD, Mell LK, Kong C, et al. A randomized phase II study of chemoradiation (CRT) +/- nivolumab (Nivo) with sequential safety evaluations of Nivo +/- lirilumab (Liri) or ipilumumab (Ipi) concomitant with (C) RT in intermediate (IR) and high-risk (HR) head and neck squamous cell carcinoma (HNSCC). Journal of Clinical Oncology (Annual Meeting of the American Society of Clinical Oncology, ASCO; 2017; United States) 2017;35(15 Suppl 1):S6097.
Gollin 1972 {published data only}
    1. Gollin FF, Ansfield FJ, Brandenburg JH, Ramirez G, Vermund H. Combined therapy in advanced head and neck cancer: a randomized study. American Journal of Roentgenology, Radium Therapy & Nuclear Medicine 1972;114(1):83-8. - PubMed
    1. Lo TC, Wiley AL Jr, Ansfield FJ, Brandenburg JH, Davis HL Jr, Gollin FF, et al. Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study. American Journal of Roentgenology 1976;126(2):229-35. - PubMed
Grandis 2008 {published data only}
    1. Grandis JR, Lai SY, Esteve FR, Kim SW, Ferris RL, Gibson MK, et al. Erlotinib (E) as adjuvant treatment for patients (pts) with resected head and neck squamous cell carcinoma (HNSCC) with evaluation of neoadjuvant biomarker modulation with E with or without sulindac (S): a feasibility report. Journal of Clinical Oncology (ASCO Annual Meeting Proceedings) 2008;26:325.
Grose 1985 {published data only}
    1. Grose WE, Lehane DE, Dixon DO, Fletcher WS, Stuckey WJ. Comparison of methotrexate and cisplatin for patients with advanced squamous cell carcinoma of the head and neck region: a Southwest Oncology Group Study. Cancer Treatment Reports 1985;69(6):577-81. - PubMed
Groselj 2017 {published data only}
    1. Groselj A, Bosnjak M, Strojan P, Krzan M, Cemazar M, Sersa G. Efficiency of electrochemotherapy with reduced bleomycin dose in the treatment of nonmelanoma head and neck skin cancer: preliminary results. Head and Neck 2017;40(1):120-5. - PubMed
Gupta 2017 {published data only}
    1. Gupta K, Dabas S. Oncological outcome following intensification of treatment by transoral robotic surgery (TORS) for HPV negative stage IV oropharyngeal cancer: a prospective trial. Annals of Oncology 2017;28:x100-10. - PubMed
Haas 1985 {published data only}
    1. Haas C, Byhardt R, Cox J, Duncovage J, Grossman T, Haas J, et al. Randomized study of 5-fluorouracil (F) and cis-platinum (P) as initial therapy of locally advanced squamous carcinoma of the head and neck (LASCHN): a preliminary analysis. In: Proceedings of the American Society of Clinical Oncology. Vol. 4. 1985:143.
Haas 1986 {published data only}
    1. Haas C, Anderson T, Byhardt R, Cox J, Duncavage J, Grossman T, et al. Randomized neo-adjuvant study of 5-fluorouracil and cis-platinum for patients with advanced resectable head and neck squamous cancer. In: Proceedings of the American Association for Cancer Research (AACR). Vol. 27. 1986:185.
    1. Haas C, Byhardt R, Cox J, Duncovage J, Grossman T, Haas J, et al. Randomized study of 5-fluorouracil (F) and cis-platinum (P) as initial therapy of locally advanced squamous carcinoma of the head and neck (LASCHN): a preliminary analysis. In: Proceedings of the American Society of Clinical Oncology. Vol. 4. 1985:143.
Haffty 1993 {published data only}
    1. Haffty BG, Son YH, Sasaki CT, Papac R, Fischer D, Rockwell S, et al. Mitomycin C as an adjunct to postoperative radiation therapy in squamous cell carcinoma of the head and neck: results from two randomized clinical trials. International Journal of Radiation Oncology, Biology, Physics 1993;27(2):241-50. - PubMed
Haffty 1997 {published data only}
    1. Haffty BG, Son YH, Papac R, Sasaki CT, Weissberg JB, Fischer D, et al. Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck: results of the Yale mitomycin randomized trials. Journal of Clinical Oncology 1997;15(1):268-76. - PubMed
    1. Hafty BG, Son YH, Papac R, Sasaki CT, Fischer D, Rockwell S, et al. Chemotherapy as an adjunct to radiation therapy (RT) in the treatment of squamous cell carcinoma, a (SCC) of the head and neck (H and N): results of the Yale mitomycin C (MC) randomized trials. In: Proceedings of the American Society of Clinical Oncology. 1996:(Abs No 893). - PubMed
Haffty 1997a {published data only}
    1. Haffty BG, Son YH, Wilson LD, Papac R, Fischer D, Rockwell S, et al. Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck. Radiation Oncology Investigations 1997;5(5):235-45. - PubMed
Haffty 2005 {published data only}
    1. Haffty B, Son YH, Wilson LD, Cho EI, Papac RJ. Concurrent chemo-radiotherapy with mitomycin C compared with porfiromycin in squamous cell cancer of the head and neck: final results of a randomized clinical trial. International Journal of Radiation Oncology, Biology, Physics 2003;57 Suppl 2:S246. - PubMed
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Haselow 1990 {published data only}
    1. Haselow RE, Warshaw ME, Oken MM, Adams GL, Aughey JL, Cooper JS, et al. Radiation alone versus radiation with weekly low dose cis-platinum in unresectable cancer of the head and neck. In: Fee WR Jr, Goepfert H, Johns ME, editors(s). Head and Neck Cancer. Vol. II. Philadelphia: B C Decker, 1990:279-81.
Henk 1984 {published data only}
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Hitt 2005 {published data only}
    1. Hitt R, Grau J, Lopez-Pousa A, Berrocal A, Garcia-Giron C, Belon J, et al. Randomized phase II/III clinical trial of induction chemotherapy (ICT) with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin/5-fluorouracil (TPF) followed by chemoradiotherapy (CRT) vs. CRT alone for patients (pts) with unresectable locally advanced head and neck cancer (LAHNC). Journal of Clinical Oncology 2006;24:18S (Abs No 5515).
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Homma 2004 {published data only}
    1. Homma A, Shirato H, Furuta Y, Nishioka T, Oridate N, Tsuchiya K, et al. Randomized phase II trial of concomitant chemoradiotherapy using weekly carboplatin or daily low-dose cisplatin for squamous cell carcinoma of the head and neck. Cancer Journal 2004;10(5):326-32. - PubMed
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    1. Iyer NG, Tan DSW, Tan VK, Wang W, Hwang W, Tan NC, et al. Erratum: randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer 2015;121(19):3560. - PubMed
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Kaneda 1987 {published data only}
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Kotani 1994 {published data only}
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Ksiezniak‐Baran 2020 {published data only}
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Laccourreye 1983 {published data only}
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Lee 1989 {published data only}
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Li 2018 {published data only}
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Lim 2020 {published data only}
    1. Lim SH, Sun JM, Hong J, Oh D, Ahn YC, Chung MK, et al. Induction chemotherapy followed by concurrent chemoradiotherapy versus CCRT for locally advanced hypopharynx and base of tongue cancer. Korean Journal of Internal Medicine 2020;36(Suppl 1):S217-24. - PMC - PubMed
Lippman 1988 {published data only}
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Liverpool HNOG 1990 {published data only}
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Lopes 1991 {published data only}
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Machiels 2016 {published data only}
    1. Machiels JP, Van Maanen A, Vandenbulcke JM, Filleul B, Seront E, Henry S, et al. Randomized phase II study of cabazitaxel versus methotrexate in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck previously treated with platinum-based therapy. Oncologist 2016;21(12):1416-7. - PMC - PubMed
Machiels 2017 {published data only}
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Machtay 2004 {published data only}
    1. Machtay M, Pajak T, Suntharalingam M, Herschock D, Stripp DC, Cmelak A, et al. Definitive radiotherapy +/- erythropoietin for squamous cell carcinoma of the head and neck: preliminary report of RTOG 99-03. International Journal of Radiation Oncology, Biology and Physics 2004;60(1 Suppl):S132.
Mackiewicz 2017 {published data only}
    1. Mackiweicz Z, Rybarcyzyk-Kasiuchnicz A, Lasinska I, Mazur-Roszak M, Swiniuch D, Michalak M, et al. The comparison of acute toxicity in 2 treatment courses: three-weekly and weekly cisplatin treatment administered with radiotherapy in patients with head and neck squamous cell carcinoma. Medicine 2017;96(51):e9151. - PMC - PubMed
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Manocha 2006 {published data only}
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Mashkour 2020 {published data only}
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    1. Mehanna HM, Sen M, Chester JD, Sanghera P, Paleri V, Gaunt P, et al. Phase III randomised controlled trial (RCT) comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer (CompARE). Journal of Clinical Oncology 2017;35:TPS6091. - PMC - PubMed
Melotek 2016 {published data only}
    1. Melotek JM, Haraf DJ, Blair EA, Witt ME, Brisson RJ, Dekker A, et al. Final results of a randomized phase 2 trial investigating the addition of cetuximab to induction chemotherapy and accelerated or hyperfractionated chemoradiation therapy for locoregionally advanced head and neck cancer: hPV-negative subset analysis. International Journal of Radiation Oncology, Biology and Physics 2016;94(4):867. [DOI: 10.1016/j.ijrobp.2015.12.029] - DOI - PubMed
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Melotek J 2016 {published data only}
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Melotek JM 2016 {published data only}
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Merlano 2020 {published data only}
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Morton 1985 {published data only}
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Morton 1987 {published data only}
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Nichols 2013 {published data only}
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Nissenbaum 1984 {published data only}
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Panis 1984 {published data only}
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Pearlman 1985 {published data only}
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Phillips 1980 {published data only}
    1. Phillips TL, Silverberg IJ, Fu KK, Friedman MA, Torti F, Kohler M, et al. Interim report on a phase III study of bleomycin and methotrexate with radiotherapy in the treatment of inoperable head and neck cancer. International Journal of Radiation Oncology, Biology, Physics 1980;6(10):1447.
Platzer 1990 {published data only}
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Poddar 2017 {published data only}
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Pothamsetty 2017 {published data only}
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Price 1978 {published data only}
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Racadot 2008 {published data only}
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Rades 2016 {published data only}
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Rastogi 2019 {published data only}
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Rodrigo 2004 {published data only}
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Rosen 2003 {published data only}
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Rosenthal 2016 {published data only}
    1. Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, et al. 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. Journal of Clinical Oncology 2016;34(12):1300-8. - PMC - PubMed
Roy 2016 {published data only}
    1. Roy B, Choudhury KB, Ghosh K, Choudhury K, Dasgupta P. A prospective randomized study of locally advanced head and neck cancer comparing concomitant chemoradiotherapy versus pure accelarated radiotherapy. Journal of Cancer Research and Therapeutics (38th Annual Conference of the Association of Radiation Oncologists of India, AROICON 2016) 2016;12:S49.
Saber 2005 {published data only}
    1. Saber RA, Mohamad SS. Use of chemotherapy in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. Journal of Clinical Oncology 2005;23:5543.
Sanchiz 1990 {published data only}
    1. Sanchiz F, Milla A, Torner J, Bonet F, Artola N, Carreno L, et al. Single fraction per day versus two fractions per day versus radiochemotherapy in the treatment of head and neck cancer. International Journal of Radiation Oncology, Biology, Physics 1990;19(6):1347-50. - PubMed
Sanguineti 1999 {published data only}
    1. Sanguineti G, Corvo R, Sormani MP, Benasso M, Numico G, Bacigalupo A, et al. Chemotherapy alternated with radiotherapy in the treatment of advanced head and neck carcinoma: predictive factors of outcome. International Journal of Radiation Oncology, Biology, Physics 1999;44(1):139-47. - PubMed
Sarkar 2008 {published data only}
    1. Sarkar SK, Patra NB, Goswami J, Basu S. Comparative study of efficacy and toxicities of cisplatin vs vinorelbine as radiosensitisers in locally advanced head and neck cancer. Journal of Laryngology & Otology 2008;122(2):188-92. - PubMed
Schildhauer 2005 {published data only}
    1. Schildhauer S, Pecher G, Pollmann D, Wernecke KD, Possinger K, Luftner D. Liposomal formulated cisplatin (lipoplatin) in the treatment of squamous cell carcinoma of the head and neck (SCCHN): first safety results of a randomized phase III study. Onkologie 2005;28 Suppl 3:48.
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Schuller 1989 {published data only}
    1. Schuller DE, Laramore G, Al Sarraf M, Jacobs J, Pajak TF. Combined therapy for resectable head and neck cancer. A phase 3 intergroup study. Archives of Otolaryngology - Head & Neck Surgery 1989;115(3):364-8. - PubMed
Scwiecicki 2016 {published data only}
    1. Swiecicki PL, Bellile E, Sacco AG, Pearson AT, Taylor JMG, Jackson TL, et al. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer. Investigational New Drugs 2016;34(4):481-9. - PMC - PubMed
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Sharma 2007 {published data only}
    1. Sharma A, Mohanti BK, Thakar A, Bahadur S, Bhasker S, Bahl A. Concomitant chemoradiation versus radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: final result of a phase III trial. Journal of Clinical Oncology 2007;25(18S):6030. - PubMed
Sharma 2019 {published data only}
    1. Sharma A, Chaudhary MK, Thakar A, Bhaskar S, Sikka K, Pramanik R, et al. Concurrent chemotherapy and external radiation therapy: an open label non-inferiority phase III randomized controlled trial of weekly versus three weekly cisplatin and radical radiotherapy in locally advanced head and neck squamous cell carcinoma: CONCERT trial. Annals of Oncology 2019;30:V473-4.
Shaw 1978 {published data only}
    1. Shaw HJ, Price LA, Hill BT, Calvert AH, Dalley VM, Levene A. A randomized combination chemotherapy trial, with and without adriamycin, in squamous cell carcinoma of the head and neck. Otolaryngology 1978;86(6 Pt 1):ORL-50. - PubMed
Shetty 1985 {published data only}
    1. Shetty P, Mehta A, Shinde S, Mazumdar A, Hingorani C. Controlled study in squamous cell carcinoma of base of tongue using conventional radiation, radiation with single drug, and radiation with multiple drug chemotherapy. In: Proceedings of the Annual Meeting of the American Society of Clinical Oncology. Vol. 4. 1985:152.
Siodlak 1989 {published data only}
    1. Siodlak MZ, Dalby JE, Bradley PJ, Campbell JB, Strickland P, Fraser JG, et al. Induction VBM plus radiotherapy, versus radiotherapy alone for advanced head and neck cancer: long-term results. Clinical Otolaryngology & Allied Sciences 1989;14(1):17-22. - PubMed
Siu 2017 {published data only}
    1. Siu LL, Waldron JN, Chen BSE, Winquist E, Wright JR, Nabid A, et al. Effect of standard radiotherapy with cisplatin vs accelerated radiotherapy with panitumumab in locoregionally advanced squamous cell head and neck carcinoma: a randomized clinical trial. JAMA Oncology 2017;3(2):220-6. - PubMed
Skillington 2017 {published data only}
    1. Skillington SA, Kallogjeri D, Lewis JS, Piccirillo JF. The role of adjuvant chemotherapy in surgically managed, p16-positive oropharyngeal squamous cell carcinoma. JAMA Otolaryngology 2017;143(3):253-9. - PMC - PubMed
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    1. Smid L, Budihna M, Zakotnik B, Soba E, Strojan P, Fajdiga I, et al. Postoperative concomitant irradiation and chemotherapy with mitomycin C and bleomycin for advanced head-and-neck carcinoma. International Journal of Radiation Oncology, Biology, Physics 2003;56(4):1055-62. - PubMed
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    1. Specenier PM, Remenar E, Buter J, Schrijvers DL, Bergamini C, Licitra LF, et al. TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial. Annals of Oncology 2017;28(9):2219-24. - PubMed
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Stefani 1980 {published data only}
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Stell 1983 {published data only}
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Stell 1990 {published data only}
    1. Stell PM, Allison RS, Campbell JB, Dalby JE, Dorman EB, Helliwell TR, et al. A phase III randomised trial of cisplatinum, methotrexate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. British Journal of Cancer 1990;61(2):311-5. - PMC - PubMed
Stolwijk 1985 {published data only}
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Sun 2017 {published data only}
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Sun 2020 {published data only}
    1. Sun XS, Tao Y, Le Tourneau C, Pointreau Y, Sire C, Kaminsky MC, et al. Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study. Lancet Oncology 2020;21(9):1173-87. - PubMed
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Tao 2017 {published data only}
    1. Tao YA, Auperin A, Graff P, Lapeyre M, Gregoire V, Maingon P, et al. Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and neck squamous cell carcinoma: pooled analysis of two GORTEC randomized trials. Oral Oncology 2017;71:61-6. - PubMed
Taylor 1978 {published data only}
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Taylor 1979 {published data only}
    1. Taylor SG, DeWys WD, Perlia CP, Wolter J, Slayton RE, Kosova LA, et al. A randomized comparison of two dosage schedules of methyl CCNU: three-week versus six-week treatments. Cancer 1979;44(3):824-30. - PubMed
Taylor 1984 {published data only}
    1. Taylor SG, McGuire WP, Hauck WW, Showel JL, Lad TE. A randomized comparison of high-dose infusion methotrexate versus standard-dose weekly therapy in head and neck squamous cancer. Journal of Clinical Oncology 1984;2(9):1006-11. - PubMed
Taylor 1985 {published data only}
    1. Corey JP, Caldarelli DD, Hutchinson JC Jr, Holinger LD, Taylor SG, Showel JL, et al. Surgical complications in patients with head and neck cancer receiving chemotherapy. Archives of Otolaryngology - Head & Neck Surgery 1986;112(4):437-9. - PubMed
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Taylor 1994 {published data only}
    1. Taylor SG, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. Journal of Clinical Oncology 1994;12(2):385-95. - PubMed
Taylor 1997 {published data only}
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Tian 2018 {published data only}
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Toohill 1987 {published data only}
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Tsukuda 1994 {published data only}
    1. Tsukuda M, Ogasawara H, Kaneko S, Komiyama S, Horiuchi M, Inuyama Y, et al. A prospective randomized trial of adjuvant chemotherapy with UFT for head and neck carcinoma. Head and Neck UFT Study Group. Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy] 1994;21(8):1169-77. - PubMed
Tsukuda 2005 {published data only}
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Veronesi 1985 {published data only}
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Von Heyden 1984 {published data only}
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Von Heyden 1985 {published data only}
    1. Schroder M, Von Heyden HW, Scherpe A, Borghardt J, Beyer JH, Nagel GA, et al. 2nd interim evaluation of a chemotherapy study on patients with squamous cell carcinomas of the head-neck area. A comparison of 2 therapy regimens: cis-diamminedichloroplatinum (II) and bleomycin versus methotrexate and vindesine. Onkologie 1983;6(3):114-7. - PubMed
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Weissberg 1989 {published data only}
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Wolf 2017 {published data only}
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Woods 1977 {published data only}
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Woods 1981 {published data only}
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    1. Yi J, Huang X, Xi Z, Liu S, Wang X, He X, et al. Phase III randomized trial of preoperative concurrent chemoradiotherapy versus preoperative radiotherapy for patients with locally advanced head and neck squamous cell carcinoma. Oncotarget 2017;8(27):44842-50. - PMC - PubMed
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References to studies awaiting assessment

Borel 2020 {published data only}
    1. Borel C, Sun X, Coutte A, Bera G, Zanetta S, Alfonsi M, et al. Standard versus fractionated high dose cisplatin concomitant with radiotherapy in locally advanced head & neck squamous cell cancer (LA-HNSCC): results of the GORTEC 2015-02 CisFRad randomized trial. Annals of Oncology 2020;31:660.
Bourhis 2002 {published data only}
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    1. Bourhis J, Lapeyre M, Tortochaux J, Etessami A, Wibault P, Geoffrois L, et al. Very accelerated RT versus CDDP-5FU in unresectable HNSCC: results of the GORTEC 96-01 randomized trial. Radiation Oncology 2002;64 Suppl 1:S118.
Chaukar 2020 {published data only}
    1. Chaukar D, Pai PS, Chaturvedi P, Pantvaidya G, Deshmukh A, Nair D, et al. A prospective phase II open-label randomized controlled trial to compare mandibular preservation in upfront surgery to neoadjuvant chemotherapy followed by surgery in operable oral cavity cancer. Journal of Clinical Oncology 2020;38(15 Suppl):6518. - PubMed
Fietkau 2017 {published data only}
    1. Fietkau R, Iro H, Hecht M, Hofner B, Gefeller O, Balermpas P, et al. Randomised phase-II trial of concurrent chemoradiation (CRT) for locally advanced head and neck cancer (stage III-IVB): comparing dose reduced radiotherapy (63,6 Gy) with paclitaxel/cisplatinum to standard radiotherapy (70,6 Gy) with fluorouracil/cisplatinum. Journal of Clinical Oncology 2017;35:15S.
He 2017 {published data only}
    1. He X, Yin H, Guo W, Sun X, Hu X, Yan P, et al. Ralitrexed verus 5-fluorouracil with cisplatin and concurrent radiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC): a randomized controlled multi-centered trial. Annals of Oncology 2017;28:5S.
Hitt 2009 {published data only}
    1. Hitt R, Grau JJ, Lopez-Pousa A, Berrocal A, Garcia Giron C, Irigoyen A. Final results of a randomized phase III trial comparing induction chemotherapy with cisplatin/5-FU or docetaxel/cisplatin/5-FU follow by chemoradiotherapy (CRT) versus CRT alone as first-line treatment of unresectable locally advanced head and neck cancer (LAHNC). Journal of Clinical Oncology 2009;27(15S):6009. [DOI: 10.1200/jco.2009.27.15_suppl.6009] - DOI
Kiyota 2020 {published data only}
    1. Kiyota N, Tahara M, Fujii H, Yamazaki T, Mitani H, Iwae S, et al. Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). Journal of Clinical Oncology 2020;38(15 Suppl):6502.
Suneetha 2016 {published data only}
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References to ongoing studies

ChiCTR2100041869 {published data only}
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CTRI/2021/03/032390 {published data only}
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NCT02285530 {unpublished data only}
    1. NCT02285530. GDF15 based TPF induction chemotherapy for OSCC patients [GDF15 (growth differentiation factor 15) based TPF induction chemotherapy for oral squamous cell carcinoma patients at T3/T4cN0M0 stage: a phase II randomized controlled trial]. clinicaltrials.gov/ct2/show/NCT02285530 (first received 7 November 2014).
NCT02734537 {unpublished data only}
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NCT03040999 {unpublished data only}
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NCT03117257 {unpublished data only}
    1. NCT03117257. Docetaxel and loplatin induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced SCCHN [A prospective phase II randomized clinical trial: docetaxel and loplatin induction chemotherapy followed by concurrent lobaplatin chemoradiotherapy for locally advanced head and neck squamous cell carcinoma]. clinicaltrials.gov/ct2/show/NCT03117257 (first received 17 April 2017).
NCT03258554 {unpublished data only}
    1. NCT03258554. Radiation therapy with durvalumab or cetuximab in treating patients with locoregionally advanced head and neck cancer who cannot take cisplatin [Randomized phase II/III trial of radiotherapy with concurrent MEDI4736 (durvalumab) vs. radiotherapy with concurrent cetuximab in patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin]. clinicaltrials.gov/ct2/show/NCT03258554 (first received 23 August 2017).
NCT03452137 {unpublished data only}
    1. NCT03452137. A study of atezolizumab (anti-Pd-L1 antibody) as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck [A phase III, multicenter, randomized, double-blind, placebo-controlled study of atezolizumab (anti-Pd-L1 antibody) as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck]. clinicaltrials.gov/ct2/show/NCT03452137 (first received 2 March 2018).
NCT03576417 {unpublished data only}
    1. NCT03576417. A trial evaluating the addition of nivolumab to cisplatin-RT for treatment of cancers of the head and neck (NIVOPOSTOP) [A phase III randomized trial of post-operative adjuvant nivolumab and concomitant chemo-radiotherapy in high-risk patients with resected squamous cell carcinoma of head and neck]. clinicaltrials.gov/ct2/show/NCT03576417 (first received 3 July 2018).
NCT03673735 {unpublished data only}
    1. NCT03673735. Maintenance immune check-point inhibitor following post-operative chemo-radiation in subjects with HPV-negative HNSCC (ADHERE) [A randomized phase III study on maintenance durvalumab vs placebo following post-operative concomitant chemoradiation in subjects with HPV-negative squamous cell head and neck carcinoma (HNSCC) with high risk of recurrence]. clinicaltrials.gov/ct2/show/NCT03673735 (first received 17 September 2018).
NCT03678649 {unpublished data only}
    1. NCT03678649. A prospective randomized trial of capecitabine treatment in patients with HNSCC [A prospective randomized controlled clinical trial of capecitabine treatment in patients with locally advanced squamous cell carcinoma of the head and neck after radiotherapy: phase II study]. clinicaltrials.gov/ct2/show/NCT03678649 (first received 19 September 2018).
NCT04780750 {published data only}
    1. NCT04780750 . Concurent chemoradiotherapy in head and neck cancers [Phase III study comparing concurrent chemoradiotherapy with weekly docitaxel plus cisplatin versus the standard concurrent radiotherapy with cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck]. clinicaltrials.gov/ct2/show/NCT04780750 (first received 3 March 2021).
Tao 2020 {unpublished data only}
    1. NCT02999087. Randomized trial of avelumab-cetuximab-radiotherapy versus SOCs in LA SCCHN (REACH) (REACH) [A phase III randomized trial of avelumab-cetuximab-radiotherapy versus standards of care in locally advanced squamous cell carcinoma of the head and neck]. clinicaltrials.gov/ct2/show/NCT02999087 (first received 21 December 2016).
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References to other published versions of this review

Furness 2010
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