Advertisement

Chemotherapy for Nasopharyngeal Cancer: Neoadjuvant, Concomitant, and/or Adjuvant

  • Wai Tong Ng
  • Amy T. Y. Chang
  • Sarah W. M. Lee
  • Henry C. K. Sze
  • Anne W. M. LeeEmail author
Head and Neck Cancer (J-P Machiels, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Head and Neck Cancer

Opinion Statement

Nasopharyngeal cancers are unique among other head and neck cancers, not only in epidemiology and histological characteristics, but also on treatment strategies as well. Radiotherapy is the primary treatment due to its radiosensitivity. In locally advanced stages, concurrent chemoradiation has been established to be effective to eradicate the disease and improve survival, in favor of radiotherapy alone. While increasing studies have explored the potential benefit of adding more chemotherapy to the concurrent regimen, whether adjuvant or neoadjuvant, it is generally agreed that proper patient selection is needed to stratify high-risk groups to intensify treatment and to optimize the disease outcome. Future studies are ongoing, possibly with the addition of biomarkers such as EBV DNA for risk group stratification. Refinement of patient groups that should be selected for combined modality treatment in stage II disease is also warranted.

Keywords

Nasopharyngeal carcinoma Chemotherapy Sequence Efficacy Toxicity Meta-analysis 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Wai Tong Ng, Amy T.Y. Chang, Sarah W.M. Lee, Henry C.K. Sze, and Anne W.M. Lee declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    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;16:1310–7.PubMedGoogle Scholar
  2. 2.
    Al-Sarraf M, LeBlanc M, Giri PG, et al. Superiority of five year survival with chemoradiotherapy (CT-radiotherapy) vs radiotherapy in patients (Pts) with locally advanced nasopharyngeal cancer (NPC). Intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388) phase III study: final report. Proc Am Soc Clin Oncol. 20; Abstract 905.Google Scholar
  3. 3.
    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;23:6730–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Wee J. 4th FY Khoo memorial lecture 2008: nasopharyngeal cancer workgroup—the past, the present and the future. Ann Acad Med Singap. 2008;37:606–14.PubMedGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.••
    Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, et al. Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): an update on 19 trials and 4,806 patients. Lancet Oncol. 2015;16(6):645–55. This updated meta-analysis, with a median follow-up of 7.7 years, is the first analysis to demonstrate the treatment effect of concomitant with or without adjuvant chemotherapy as distinct groups.PubMedCrossRefGoogle Scholar
  7. 7.
    Chen Y, Sun Y, Liang SB, 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;119:2230–8.PubMedCrossRefGoogle Scholar
  8. 8.
    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;24:2131–6.PubMedCrossRefGoogle Scholar
  9. 9.
    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;97:536–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Lin JC, Jan JS, Hsu CY, et al. 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;21:631–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Kwong DL, Sham JS, Au GK, et al. Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. J Clin Oncol. 2004;22:2643–53.PubMedCrossRefGoogle Scholar
  12. 12.
    Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003;21:92–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Baujat B, Audry H, Bourhis J, et al. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006;64:47–56.PubMedCrossRefGoogle Scholar
  14. 14.•
    Chen Y, Liu MZ, Liang SB, et al. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys. 2008;71:1356–64. This prospective randomized trial demonstrated superior outcome for NPC patient treatment with concurrent chemotherapy and adjuvant chemotherapy compared with radiotherapy alone, with significant improved 2-year OS, failure-free rate, and distant failure-free survival.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen L, Hu CS, Chen XZ, 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;13:163–71.PubMedCrossRefGoogle Scholar
  16. 16.
    What is the best treatment in nasopharyngeal carcinoma? An individual patient data network meta-analysis. Radiother Oncol. 2015; 114 (suppl 1; abstr OC003).Google Scholar
  17. 17.
    Liu N, Chen NY, Cui RX, et al. Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol. 2012;13:633–41.PubMedCrossRefGoogle Scholar
  18. 18.
    Wang HY, Sun BY, Zhu ZH, et al. Eight-signature classifier for prediction of nasopharyngeal [corrected] carcinoma survival. J Clin Oncol. 2011;29:4516–25.PubMedCrossRefGoogle Scholar
  19. 19.
    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;27:242–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Fountzilas G, Ciuleanu E, Bobos M, et al. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Ann Oncol. 2012;23:427–35.PubMedCrossRefGoogle Scholar
  21. 21.
    Tan T, Lim WT, Fong KW, et al. Concurrent chemo-radiation with or without induction gemcitabine, carboplatin, and paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2015;91:952–60.PubMedCrossRefGoogle Scholar
  22. 22.•
    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;121:1328–38. This six-arm randomized phase 3 trial conducted by the Hong Kong Nasopharyngeal Cancer Study Group showed improvement of outcome using induction PX (cisplatin and capecitabine); adjusted comparison of induction PX versus induction or adjuvant PF demonstrated lower hazard ratio of death or progression and less toxicity.PubMedCrossRefGoogle Scholar
  23. 23.
    Daoud J, Aupérin A, Tao YG, et al. A randomized trial of concomitant cisplatin-RT +/− induction TPF in locally advanced nasopharyngeal carcinomas. Radiother Oncol. 2015;114 Supp. 1 Abstract OC-004.Google Scholar
  24. 24.
    Sun Y, Chen NY, Zhang N, Hu GQ. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregional advanced nasopharyngeal carcinoma: preliminary results of a phase 3 multicentre randomized controlled trial. The Croucher Foundation Advanced Study Institute–Advances in Nasopharyngeal Carcinoma Studies. 2014.Google Scholar
  25. 25.
    Chua DT, Ma J, Sham JS, et al. Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: subgroup analysis of two phase III trials. Int J Radiat Oncol Biol Phys. 2006;65:1300–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Song CH, Wu HG, Heo DS, et al. Treatment outcomes for radiotherapy alone are comparable with neoadjuvant chemotherapy followed by radiotherapy in early-stage nasopharyngeal carcinoma. Laryngoscope. 2008;118:663–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Cheng SH, Tsai SY, Yen KL, et al. Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma. J Clin Oncol. 2000;18:2040–5.PubMedGoogle Scholar
  28. 28.•
    Chen QY, Wen YF, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011;103:1761–70. This randomized study demonstrates benefit of concurrent chemoradiation in stage II nasopharyngeal cancer patients, with significant improvement in 5-year OS, PFS, and distant metastasis-free survival.PubMedCrossRefGoogle Scholar
  29. 29.
    Loong HH, Ma BB, Leung SF, et al. Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Radiother Oncol. 2012;104:300–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee AW, Ng WT, Chan LL, et al. Evolution of treatment for nasopharyngeal cancer—success and setback in the intensity-modulated radiotherapy era. Radiother Oncol. 2014;110:377–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Su SF, Han F, Zhao C, et al. Long-term outcomes of early-stage nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy alone. Int J Radiat Oncol Biol Phys. 2012;82:327–33.PubMedCrossRefGoogle Scholar
  32. 32.
    Xiao WW, Han F, Lu TX, et al. Treatment outcomes after radiotherapy alone for patients with early-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2009;74:1070–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Chua DT, Sham JS, Kwong DL, et al. Treatment outcome after radiotherapy alone for patients with stage I-II nasopharyngeal carcinoma. Cancer. 2003;98:74–80.PubMedCrossRefGoogle Scholar
  34. 34.
    Ng WT, Yuen KT, Au KH, et al. Staging of nasopharyngeal carcinoma—the past, the present and the future. Oral Oncol. 2014;50:549–54.PubMedCrossRefGoogle Scholar
  35. 35.
    Leung SF, Chan AT, Zee B, et al. Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type. Cancer. 2003;98:288–91.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Wai Tong Ng
    • 1
  • Amy T. Y. Chang
    • 1
  • Sarah W. M. Lee
    • 1
  • Henry C. K. Sze
    • 2
  • Anne W. M. Lee
    • 2
    Email author
  1. 1.Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalChai WanHong Kong
  2. 2.Clinical Oncology CenterUniversity of Hong Kong-Shenzhen HospitalShenzhenChina

Personalised recommendations