Skip to main navigation menu Skip to main content Skip to site footer
Brazilian Journal of Clinical Medicine and Review

Health Review

Vol. 3 No. 1 (2025): January/December - 2025

Evaluation of Head and Neck Squamous Cell Cancer Treatment and Outcomes: Low-Dose Nivolumab in Palliative Treatment, A Literature Review

DOI
https://doi.org/10.52600/2965-0968.bjcmr.2025.3.1.bjcmr14
Submitted
July 12, 2024
Published
2024-09-11

Abstract

The chemotherapy treatment based on Taxol, paclitaxel is widely used in the treatment of neoplastic conditions in the head and neck, however in the last decades immunotherapy has made a revolution in the context of oncological treatments. The Anti-PDL1 agent, Nivolumab, has been proving to be of great value in the treatment of solid tumors. Through the review method this study aims to synthesize and analyze treatments for advanced head and neck cancer, in addition to critically analyzing existing studies on the use of reduced doses of nivolumab in patients with head and neck cancer. Thus, we aim to elucidate the action of oncological agents used in the treatment of SCC, as well as confirm the superiority of immunotherapeutic treatment in cases of advanced stage SCC.

References

  1. D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case–control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944-1956. doi: 10.1056/NEJMoa065497.
  2. Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst. 2007;99(10):777-789. doi: 10.1093/jnci/djk179.
  3. Dasgupta S, Bhattacharya-Chatterjee M, O'Malley BW Jr, Chatterjee SK. Emerging strategies for the early detection and prevention of head and neck squamous cell cancer. J Cell Physiol. 2012;227(2):467-473. doi: 10.1002/jcp.22767.
  4. Hu D, Goldie SJ. The economic burden of noncervical human papillomavirus disease in the United States. Am J Obstet Gynecol. 2008;198(5):500.e1-7. doi: 10.1016/j.ajog.2008.03.064.
  5. Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008;359(11):1143-1154.
  6. Torrente MC, Rodrigo JP, Haigentz M Jr, Dikkers FG, Rinaldo A, Takes RP, et al. Human papillomavirus infections in laryngeal cancer. Head Neck. 2011;33(4):581-586. doi: 10.1002/hed.21421.
  7. Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME, Tran HH, et al. EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 2008;26(19):3128-3137. doi: 10.1200/JCO.2007.12.7662.
  8. Boehm A, Wolff KD, Boulekos D, Reiter R, Otto M, Kolk A, et al. Current therapy options in recurrent head and neck cancer. HNO. 2010;58(9):762-769.
  9. Karatzanis AD, Psychogios G, Waldfahrer F, Zenk J, Hornung J, Iro H, et al. T1 and T2 hypopharyngeal cancer treatment with laser microsurgery. J Surg Oncol. 2010;102(1):27-33. doi: 10.1002/jso.21550.
  10. Shin DM, Khuri FR. Advances in the management of recurrent or metastatic squamous cell carcinoma of the head and neck. Head Neck. 2011 [Epub ahead of print].
  11. Wood DE. National Comprehensive Cancer Network (NCCN) clinical practice guidelines for lung cancer screening. Thorac Surg Clin. 2015;25(2):185-197.
  12. Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Taylor SG, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol. 1992;10(8):1245-1251. doi: 10.1200/JCO.1992.10.8.1245.
  13. Catimel G, Vermorken JB, Clavel M, Bugat R, Kahamba J, Claude JR, et al. A phase II study of gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck. Ann Oncol. 1994;5(6):543-547.
  14. Testolin A, Nicolin G, Quercia S, Atzori F, Zaniboni A, Pansini A. Vinorelbine in pre-treated advanced head & neck squamous cell carcinoma: A phase II study. Invest New Drugs. 1994;12(3):231-234. doi: 10.1007/BF00873964.
  15. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton R, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019a;393(10166):51-60. doi: 10.1016/S0140-6736(18)32752-1.
  16. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton R, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Int J Radiat Oncol Biol Phys. 2019b;105(1):58-65. doi: 10.1016/j.ijrobp.2003.11.032.
  17. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116-1127.
  18. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. doi: 10.1056/NEJMoa1602252.
  19. Cohen EE, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8.
  20. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225-249. doi: 10.3322/caac.20006.
  21. Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, et al. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer. 2003;105(5):681-686. doi: 10.1002/ijc.11114.
  22. Gillison ML. Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck. 2007;29(8):779-792. doi: 10.1002/hed.20573.
  23. Marron M, Boffetta P, Zhang ZF, Zaridze D, Wünsch-Filho V, Winn DM, et al. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol. 2010;39(1):182-196. doi: 10.1093/ije/dyp291.
  24. Liang C, McClean MD, Marsit C, Christensen B, Peters E, Nelson HH, et al. Gene–environment interactions of novel variants associated with head and neck cancer. Head Neck. 2012;34(8):1111-1118. doi: 10.1002/hed.21867.
  25. Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(4):489-501. doi: 10.4065/83.4.489.
  26. Bisht M, Bist SS. Human papilloma virus: a new risk factor in a subset of head and neck cancers. J Cancer Res Ther. 2011;7(3):251-255. doi: 10.4103/0973-1482.87004.
  27. Choi S, Myers JN. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 2008;87(1):14-32. doi: 10.1177/154405910808700104.
  28. Gaudet MM, Olshan AF, Weissler MC, Watson M, Bell DA, Funkhouser WK, et al. Body mass index and risk of head and neck cancer in a pooled analysis of case–control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Int J Epidemiol. 2010;39(4):1091-1102. doi: 10.1093/ije/dyp380.
  29. Chuang SC, Jenab M, Heck JE, Bosetti C, Talamini R, Matsuo K, et al. Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium. Cancer Causes Control. 2012;23:69-88.
  30. Kyzas PA, Evangelou E, Denaxa-Kyza D, Ioannidis JP. 18F-fluorodeoxyglucose positron emission tomography to evaluate cervical node metastases in patients with head and neck squamous cell carcinoma: a meta-analysis. J Natl Cancer Inst. 2008;100(10):712-720. doi: 10.1093/jnci/djn125.
  31. Kuno H, Onaya H, Fujii S, Oshima H, Fujita A, Tomori H, et al. Comparison of MR imaging and dual-energy CT for the evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma. AJNR Am J Neuroradiol. 2018;39(3):524-531. doi: 10.3174/ajnr.A5530.
  32. Haque R, Contreras R, McNicoll MP. Surgical margins and survival after head and neck cancer surgery. BMC Ear Nose Throat Disord. 2006;6:2.
  33. Sessions DG, Spector GJ, Lenox J, Haughey B, Chao KS. Analysis of treatment results for floor‐of‐mouth cancer. Laryngoscope. 2000;110(10):1764-1772. doi: 10.1097/00005537-200010000-00038.
  34. Duprez F, Madani I, Bonte K, Deron P, De Gersem W, De Neve W. Intensity-modulated radiotherapy for recurrent and second primary head and neck cancer in previously irradiated territory. Radiother Oncol. 2009;93(3):563-569. doi: 10.1016/j.radonc.2009.10.012.
  35. Budach W, Hehr T, Budach V, Belka C, Dietz K. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer. 2006;6:28.
  36. Jham BC, Freire AR. Oral complications of radiotherapy in the head and neck. Braz J Otorhinolaryngol. 2006;72(5):704-708. doi: 10.1016/S1808-8694(15)31029-6.
  37. Santos RCS, Albernaz FP, Vilela BG, Anami EH, Rauber EA, Alves da Silva RA, et al. Mucositis in head and neck cancer patients undergoing radiochemotherapy. Rev Esc Enferm USP. 2011;45(6):1338-1344. doi: 10.1590/S0080-62342011000600009.
  38. Zitsch RP. Carcinoma of the lip. Otolaryngol Clin North Am. 1993;26(2):265-277.
  39. de Visscher JG, van den Elsacker AJ, Grond AJ, Botke G, van der Waal I. Surgical treatment of squamous cell carcinoma of the lower lip: evaluation of long-term results and prognostic factors—a retrospective analysis of 184 patients. J Oral Maxillofac Surg. 1998;56(7):814-820. doi: 10.1016/s0278-2391(98)90001-5.
  40. Studer G, Ambühl E, Brown M, Riesterer O, Glanzmann C. IMRT in oral cavity cancer. Radiat Oncol. 2007;2(1):16. doi: 10.1186/1748-717X-2-16.
  41. Petersen JF, Lansaat L, Grutters JPC, Pameijer FA, Burlage FR, van Herpen CML, et al. Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands. Eur Arch Otorhinolaryngol. 2018;275(1):181-189. doi: 10.1007/s00405-017-4766-6.
  42. Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012;13(2):145-153. doi: 10.1016/S1470-2045(11)70346-1.
  43. Shah JP, Gil Z. Current concepts in management of oral cancer–surgery. Oral Oncol. 2009;45(4-5):394-401. doi: 10.1016/j.oraloncology.2008.05.017.
  44. Kao J, Garofalo MC, Milano MT, Chmura SJ, Citron JR, Haraf DJ, et al. Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage. Int J Radiat Oncol Biol Phys. 2008;71(2):362-370. doi: 10.1016/j.ijrobp.2007.09.058.
  45. Iyer NG, Tan DS, Tan VK, Wang W, Hwang J, Tan NC, et al. 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(10):1599-1607. doi: 10.1002/cncr.29251.
  46. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937-1944. doi: 10.1056/NEJMoa032646.
  47. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21-28. doi: 10.1016/S1470-2045(09)70311-0.
  48. Lacas B, Carmel A, Landais C, Sire C, Geoffrois L, Martin L, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021;156:281-293. doi: 10.1016/j.radonc.2021.01.013.
  49. Sharma A, Saxena A, Roychoudhury A, Pandey S, Mohanti BK, Bahadur S. An open-label, noninferiority phase III RCT of weekly versus three weekly cisplatin and radical radiotherapy in locally advanced head and neck squamous cell carcinoma (ConCERT trial). J Clin Oncol. 2022;40(16_suppl):6004. doi: 10.1200/JCO.2022.40.16_suppl.6004.
  50. Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991;324(24):1685-1690.
  51. Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. J Natl Cancer Inst. 1996;88(13):890-899. doi: 10.1093/jnci/88.13.890.
  52. Sherman EJ, Luginbuhl A, Berson A, Zundel M, Desai R, Patel UA, et al. TALK score: development and validation of a prognostic model for predicting larynx preservation outcome. Laryngoscope. 2012;122(5):1043-1050. doi: 10.1002/lary.23220.
  53. Grover S, Swisher-McClure S, Mitra N, Li T, Cohen RB, Ahn PH, et al. Total laryngectomy versus larynx preservation for T4a larynx cancer: patterns of care and survival outcomes. Int J Radiat Oncol Biol Phys. 2015;92(3):594-601. doi: 10.1016/j.ijrobp.2015.03.004.
  54. Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEY-NOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7.
  55. Burtness B, Bauml JM, Galloway TJ, Gilbert J, Langer C, Aggarwal C, et al. Abstract LB-258: efficacy of first-line (1L) pem-brolizumab by PD-L1 combined positive score <1, 1-19, and ≥20 in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): KEYNOTE-048 subgroup analysis. Cancer Res. 2020;80(16_Supplement). doi: 10.1158/1538-7445.AM2020-LB-258.
  56. Patil VM, Noronha V, Joshi A, Gudipudi A, Banavali S, Mahajan A, et al. Phase 3 randomised study evaluating the addition of low-dose nivolumab to palliative chemotherapy in head and neck cancer. J Clin Oncol. 2022;40(17_suppl):6005.