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Cytotoxic Chemotherapy and Targeted Therapy in Nasopharyngeal Cancer

  • Jonathan Pan
  • Jennifer Johnson
  • Athanassios Argiris
Chapter

Abstract

Over the past several decades, there has been a notable decrease in the incidence and mortality of nasopharyngeal carcinoma. Lifestyle modification, improvements in screening and diagnosis, and advances in radiation and systemic therapy have all contributed to these favorable trends. In this chapter, we review current treatment methods in localized and recurrent/metastatic disease, with an emphasis on systemic therapy. Additionally, we explore the potential role of Epstein-Barr virus in determining treatment strategy and evaluate newer targeted therapies, including immunotherapy, which may become standard treatment options in the future.

Keywords

Nasopharyngeal carcinoma Epstein-Barr virus Intensity-modulated radiotherapy Chemotherapy Immunotherapy 

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):359.CrossRefGoogle Scholar
  2. 2.
    Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomark Prev. 2006;15(10):1765–77.CrossRefGoogle Scholar
  3. 3.
    Tang L, Chen W, Xue W, et al. Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer Lett. 2016;374(1):22–30.CrossRefGoogle Scholar
  4. 4.
    Nicholls JM. Nasopharyngeal carcinoma: classification and histologic appearances. Adv Anat Pathol. 1997;4(2):71–84.CrossRefGoogle Scholar
  5. 5.
    Barnes L, Eveson JW, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: International Agency of Research on Cancer; 2005.Google Scholar
  6. 6.
    Maxwell JH, Kumar B, Feng FY, et al. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32(5):562–7.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Lin Z, Khong B, Kwok S, et al. Human papillomavirus 16 detected in nasopharyngeal carcinomas in white Americans but not in endemic Southern Chinese patients. Head Neck. 2014;36(5):709–14.CrossRefGoogle Scholar
  8. 8.
    Huang WB, Chan JYW, Liu DL. Human papillomavirus and World Health Organization type III nasopharyngeal carcinoma: multicenter study from an endemic area in Southern China. Cancer. 2018;124(3):530–6.CrossRefGoogle Scholar
  9. 9.
    Dogan S, Hedberg ML, Ferris RL, Rath TJ, Assaad AM, Chiosea SI. Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a low-incidence population. Head Neck. 2014;36(4):511–6.CrossRefGoogle Scholar
  10. 10.
    Stenmark MH, McHugh JB, Schipper M, et al. Nonendemic HPV-positive nasopharyngeal carcinoma: association with poor prognosis. Int J Radiat Oncol Biol Phys. 2014;88(3):580–8.CrossRefGoogle Scholar
  11. 11.
    Tse K, Su W, Chang K, et al. Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3. Am J Hum Genet. 2009;85(2):194–203.CrossRefGoogle Scholar
  12. 12.
    Bei J, Li Y, Jia W, et al. A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet. 2010;42(7):599.CrossRefGoogle Scholar
  13. 13.
    Hsu W, Tse K, Liang S, et al. Evaluation of human leukocyte antigen-A (HLA-A), other non-HLA markers on chromosome 6p21 and risk of nasopharyngeal carcinoma. PLoS One. 2012;7(8):e42767.CrossRefGoogle Scholar
  14. 14.
    Chua ML, Wee JT, Hui EP, Chan AT. Nasopharyngeal carcinoma. Lancet. 2016;387(10022):1012–24.CrossRefGoogle Scholar
  15. 15.
    Lee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol. 2009;27(22):3684.CrossRefGoogle Scholar
  16. 16.
    Peng G, Wang T, Yang K, et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012;104(3):286–93.CrossRefGoogle Scholar
  17. 17.
    Lee AW, Tung SY, Chan AT, et al. A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma. Radiother Oncol. 2011;98(1):15–22.CrossRefGoogle Scholar
  18. 18.
    Lee AW, Ngan RK, Tung SY, et al. Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer. 2015;121(8):1328–38.CrossRefGoogle Scholar
  19. 19.
    Lee AW, Sze WM, Au JS, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005;61(4):1107–16.CrossRefGoogle Scholar
  20. 20.
    Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16(4):1310–7.CrossRefGoogle Scholar
  21. 21.
    Chen Q, Wen Y, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011;103(23):1761–70.CrossRefGoogle Scholar
  22. 22.
    Lee AW, Tung SY, Ngan RK, et al. Factors contributing to the efficacy of concurrent–adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 trials. Eur J Cancer. 2011;47(5):656–66.CrossRefGoogle Scholar
  23. 23.
    Liang H, Xia W, Lv X, et al. Concurrent chemoradiotherapy with 3-weekly versus weekly cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial (ChiCTR-TRC-12001979). J Clin Oncol. 2017;35(15 Suppl):6006.CrossRefGoogle Scholar
  24. 24.
    Lee JY, Sun J, Oh DR, et al. Comparison of weekly versus triweekly cisplatin delivered concurrently with radiation therapy in patients with locally advanced nasopharyngeal cancer: a multicenter randomized phase II trial (KCSG-HN10-02). Radiother Oncol. 2016;118(2):244–50.CrossRefGoogle Scholar
  25. 25.
    Zhang L, Zhao C, Peng P, et al. Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol. 2005;23(33):8461–8.CrossRefGoogle Scholar
  26. 26.
    Wu X, Huang PY, Peng PJ, et al. Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma. Ann Oncol. 2013;24(8):2131–6.CrossRefGoogle Scholar
  27. 27.
    Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007;43(9):1399–406.CrossRefGoogle Scholar
  28. 28.
    Chen L, Hu C, Chen X, Hu G, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012;13(2):163–71.CrossRefGoogle Scholar
  29. 29.
    Chen L, Hu C, Chen X, et al. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer. 2017;75:150–8.CrossRefGoogle Scholar
  30. 30.
    Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015;16(6):645–55.CrossRefGoogle Scholar
  31. 31.
    Ribassin-Majed L, Marguet S, Lee AW, et al. What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis. J Clin Oncol. 2017;35:498.CrossRefGoogle Scholar
  32. 32.
    Chan AT, Lo YD, Zee B, et al. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst. 2002;94(21):1614–9.CrossRefGoogle Scholar
  33. 33.
    Chan AT, Ngan RK, Hui EP, et al. A multicenter randomized controlled trial (RCT) of adjuvant chemotherapy (CT) in nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA (EBV DNA) following primary radiotherapy (RT) or chemoradiotherapy (CRT). J Clin Oncol. 2017;35(15 Suppl):6002.CrossRefGoogle Scholar
  34. 34.
    Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242.CrossRefGoogle Scholar
  35. 35.
    Sun Y, Li W, Chen N, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17(11):1509–20.CrossRefGoogle Scholar
  36. 36.
    Cao S, Yang Q, Guo L, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase III multicentre randomised controlled trial. Eur J Cancer. 2017;75:14–23.CrossRefGoogle Scholar
  37. 37.
    Siala W, Mnejja W, Abid M, Ghorbel A, Frikha M, Daoud J. Thyroid toxicity after radiotherapy of nasopharyngeal carcinoma. Ann Endocrinol. 2011;72(1):19–23.CrossRefGoogle Scholar
  38. 38.
    Zhang A, Fan Y, Wang X, et al. Increased treatment-related mortality with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy. Radiother Oncol. 2012;104(3):279–85.CrossRefGoogle Scholar
  39. 39.
    Sun X, Su S, Chen C, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2014;110(3):398–403.CrossRefGoogle Scholar
  40. 40.
    Ou X, Zhou X, Shi Q, et al. Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost. Oncotarget. 2015;6(35):38381.CrossRefGoogle Scholar
  41. 41.
    Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016;388(10054):1883–92.CrossRefGoogle Scholar
  42. 42.
    Jin Y, Cai X, Shi Y, et al. Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 2012;138(10):1717–25.CrossRefGoogle Scholar
  43. 43.
    Chan AT, Hsu M, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005;23(15):3568–76.CrossRefGoogle Scholar
  44. 44.
    Chua DT, Wei WI, Wong MP, Sham JS, Nicholls J, Au GK. Phase II study of gefitinib for the treatment of recurrent and metastatic nasopharyngeal carcinoma. Head Neck. 2008;30(7):863–7.CrossRefGoogle Scholar
  45. 45.
    Ma B, Hui EP, King A, et al. A phase II study of patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma and evaluation of plasma Epstein-Barr virus DNA as a biomarker of efficacy. Cancer Chemother Pharmacol. 2008;62(1):59–64.CrossRefGoogle Scholar
  46. 46.
    You B, Le Tourneau C, Chen EX, et al. A Phase II trial of erlotinib as maintenance treatment after gemcitabine plus platinum-based chemotherapy in patients with recurrent and/or metastatic nasopharyngeal carcinoma. Am J Clin Oncol. 2012;35(3):255–60.CrossRefGoogle Scholar
  47. 47.
    Elser C, Siu LL, Winquist E, et al. Phase II trial of sorafenib in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or nasopharyngeal carcinoma. J Clin Oncol. 2007;25(24):3766–73.CrossRefGoogle Scholar
  48. 48.
    Xue C, Huang Y, Huang PY, et al. Phase II study of sorafenib in combination with cisplatin and 5-fluorouracil to treat recurrent or metastatic nasopharyngeal carcinoma. Ann Oncol. 2012;24(4):1055–61.CrossRefGoogle Scholar
  49. 49.
    Hui EP, Ma B, King AD, et al. Hemorrhagic complications in a phase II study of sunitinib in patients of nasopharyngeal carcinoma who has previously received high-dose radiation. Ann Oncol. 2011;22(6):1280–7.CrossRefGoogle Scholar
  50. 50.
    Lim W, Ng Q, Ivy P, et al. A phase II study of pazopanib in Asian patients with recurrent/metastatic nasopharyngeal carcinoma. Clin Cancer Res. 2011;17(16):5481–9.CrossRefGoogle Scholar
  51. 51.
    Hui EP, Ma BB, Mo F, et al. Axitinib in recurrent or metastatic nasopharyngeal carcinoma (NPC): final result of a phase 2 clinical trial with pharmacokinetic (PK) correlation. Ann Oncol. 2016;27(6 Suppl):961.Google Scholar
  52. 52.
    Zhang J, Fang W, Qin T, et al. Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma. Med Oncol. 2015;32(3):86.CrossRefGoogle Scholar
  53. 53.
    Hsu C, Lee S, Ejadi S, et al. Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1–positive nasopharyngeal carcinoma: results of the KEYNOTE-028 study. J Clin Oncol. 2017;35(36):4050–6.CrossRefGoogle Scholar
  54. 54.
    Ma BB, Lim W, Goh B, et al. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the Mayo Clinic phase 2 consortium (NCI-9742). J Clin Oncol. 2018;36:1412.CrossRefGoogle Scholar
  55. 55.
    Delord J, Hollebecque A, De Boer JP, et al. An open-label, multicohort, phase I/II study to evaluate nivolumab in patients with virus-associated tumors (CheckMate 358): efficacy and safety in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). J Clin Oncol. 2017;35(15 Suppl):6025.CrossRefGoogle Scholar
  56. 56.
    Hui EP, Taylor GS, Jia H, et al. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res. 2014;73(6):1676–88.CrossRefGoogle Scholar
  57. 57.
    Taylor GS, Jia H, Harrington K, et al. A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. Clin Cancer Res. 2014;20(19):5009–22.CrossRefGoogle Scholar
  58. 58.
    Chia W, Teo M, Wang W, et al. Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Mol Ther. 2014;22(1):132–9.CrossRefGoogle Scholar
  59. 59.
    Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 2003;21(4):631–7.CrossRefGoogle Scholar
  60. 60.
    Chan AT, Teo PM, Ngan RK, et al. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002;20(8):2038–44.CrossRefGoogle Scholar
  61. 61.
    Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005;97(7):536–9.CrossRefGoogle Scholar
  62. 62.
    Wee J, Tan EH, Tai BC, et al. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol. 2005;23(27):6730–8.CrossRefGoogle Scholar
  63. 63.
    Chen Y, Sun Y, Liang S, et al. Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage III to IVB nasopharyngeal carcinoma from endemic regions of China. Cancer. 2013;119(12):2230–8.CrossRefGoogle Scholar
  64. 64.
    Lee AW, Tung SY, Chua DT, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010;102(15):1188–98.CrossRefGoogle Scholar
  65. 65.
    Au E, Ang P. A phase II trial of 5-fluorouracil and cisplatinum in recurrent or metastatic nasopharyngeal carcinoma. Ann Oncol. 1994;5(1):87–9.CrossRefGoogle Scholar
  66. 66.
    Stein ME, Ruff P, Weaving A, Fried J, Bezwoda WR. A phase II study of cisplatin/ifosfamide in recurrent/metastatic undifferentiated nasopharyngeal carcinoma among young blacks in southern Africa. Am J Clin Oncol. 1996;19(4):386–8.CrossRefGoogle Scholar
  67. 67.
    Yeo W, Leung TW, Leung SF, et al. Phase II study of the combination of carboplatin and 5-fluorouracil in metastatic nasopharyngeal carcinoma. Cancer Chemother Pharmacol. 1996;38(5):466–70.CrossRefGoogle Scholar
  68. 68.
    Yeo W, Leung T, Chan A, et al. A phase II study of combination paclitaxel and carboplatin in advanced nasopharyngeal carcinoma. Eur J Cancer. 1998;34(13):2027–31.CrossRefGoogle Scholar
  69. 69.
    Tan E, Khoo KS, Wee J, et al. Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma. Ann Oncol. 1999;10(2):235–7.CrossRefGoogle Scholar
  70. 70.
    McCarthy JS, Tannock IF, Degendorfer P, Panzarella T, Furlan M, Siu LL. A Phase II trial of docetaxel and cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. Oral Oncol. 2002;38(7):686–90.CrossRefGoogle Scholar
  71. 71.
    Chua DT, Sham JS, Au GK. A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. Oral Oncol. 2005;41(6):589–95.CrossRefGoogle Scholar
  72. 72.
    Ngan R, Yiu H, Lau WH, et al. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol. 2002;13(8):1252–8.CrossRefGoogle Scholar
  73. 73.
    Ma BB, Tannock IF, Pond GR, Edmonds MR, Siu LL. Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer. 2002;95(12):2516–23.CrossRefGoogle Scholar
  74. 74.
    Wang C, Chang J, Liu T, Lin C, Yu Y, Hong R. Phase II study of gemcitabine plus vinorelbine in the treatment of cisplatin-resistant nasopharyngeal carcinoma. Head Neck. 2006;28(1):74–80.CrossRefGoogle Scholar
  75. 75.
    Ma B, Hui EP, Wong S, et al. Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma—correlation with excision repair cross-complementing-1 polymorphisms. Ann Oncol. 2009;20(11):1854–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jonathan Pan
    • 1
  • Jennifer Johnson
    • 1
  • Athanassios Argiris
    • 1
  1. 1.Department of Medical OncologyThomas Jefferson UniversityPhiladelphiaUSA

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