Opinion statement
The Head and Neck Cancer Intergroup phase III clinical trial (Int 0099) for patients with locally advanced, squamous cell carcinomas (SCC) of the nasopharynx (or NPC) has been recently completed in the United States. The results of this study have defined the new standard of treatment for the group of patients studied. Patients with untreated, locally advanced stages III and IV NPC were randomized to a conven-tional course of radiation, or to radiation given concurrently with chemotherapy followed by three courses of combination chemotherapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 24% versus 69% (P < 0.001) and 46% versus 76% (P < 0.001) for the control and experimental groups, respectively. Recent updates of these survival figures show that they have not changed appreciably. The considerable improvement in OS versus PFS for the patient group receiving radiation alone is accounted for primarily by re-treatment with concurrent radiation-chemo-therapy, combination chemotherapy, and isolated salvage neck dissections. Highly significant differences in local control (41% vs 14%) and distant metastases (35% vs 13%) were demonstrated in favor of the chemoradiation treatment arm. The median age for these patients was 51 years, with a 2:1 male to female ratio. Although many patients had a significant history of tobacco exposure with or without alcohol use or abuse, only 24% had keratinizing or well-differentiated squamous (World Health Organization [WHO] I) type tumors. Whether these results can be extrapolated to the more common Asian variety (WHO II and III) of advanced NPC must be addressed in future clinical trials.
Similar content being viewed by others
References and Recommended Reading
Fandi A, Altun M, Azli N, et al.: Nasopharyngeal cancer, epidemiology, staging and treatment. Semin Oncol 1994, 21:382–397.
Ho JHC: An epidemiological and clinical study of nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1978, 4:183–197.
Lores AD, Dickson RI, Riding K, et al.: Cancer of the nasopharynx in British Columbia. Am J Clin Oncol 1986, 9:281–291.
Hsu JL, Glaser SL: Epstein-Barr virus-associated malignancies: epidemiologic patterns and etiologic implications. Crit Rev Oncol Hematol 2000, 34:27–53. Updated review of status of Epstein-Barr virus and naso-pharyngeal carcinomas.
Al-Kourainy K, Crissman J, Ensley JF, et al.: Excellent response to cis-platinum-based chemotherapy in patients with recurrent or previously untreated advanced nasopharyngeal carcinoma. Am J Clin Oncol 1988, 1:427–430.
Decker DA, Drelichman A, Crissman J, et al.: Chemo-therapy for nasopharyngeal carcinoma. A ten-year experience. Cancer 1983, 52:602–605.
Fandi A, Bachouchi M, Azli N, et al.: Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type. J Clin Oncol 2000, 18:1324–1330.
Teo PML, Kwan WH, Lee WY, et al.: Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma.Cancer 77:2423–2431.
Pathmanathan R, Prasad U, Chandrika G, et al.:Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia. Am J Pathol 1995, 146:1355–1367.
Neel HB, Pearson GR, Weiland LH, et al.: Application of Epstein-Barr virus serology to the diagnosis and staging of North American patients with naso-pharyngeal carcinoma. Otolaryngol Head Neck Surg 1983, 91:255–262.
Yip TT, Lau WH, Chan JK, et al.: Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma. Cancer 1998, 83:2284–2292. Discussion of DNA content parameters and outcome in patients with nasopharyngeal carcinomas and other parameters.
Cheng DS, Campbell BH, Clowry LJ, et al.: DNA content in nasopharyngeal carcinoma. Am J Otolaryngol 1990, 11:393–397.
Costello F, Mason BR, Collins RJ, Kearsley JH:A clinical and flow cytometric analysis of patients with nasopharyngeal cancer. Cancer 1990, 66:1789–1795.
Sung NS, Zeng Y, Raab-Traub N: Alterations on chromosome 3 in endemic and nonendemic naso-pharyngeal carcinoma. Int J Cancer 2000, 86:244–250.
Huang DP, Lo KW, van Hasselt CA, et al.: A region of homozygous deletion on chromosome 9p21-22 in primary nasopharyngeal carcinoma. Cancer Res 1994, 54:4003–4006.
Hui AB, Lo KW, Leung SF, et al.: Loss of heterozygosity on the long arm of chromosome 11 in nasopharyn-geal carcinoma. Cancer Res 1996, 56:3225–3229.
Tsang YS, Lo KW, Leung SF, et al.: Two distinct regions of deletion on chromosome 13q in primary naso-pharyngeal carcinoma. Int J Cancer 1999, 83:305–308.
Mutirangura A, Pornthanakasem W, Sriuranpong V, et al.: Loss of heterozygosity on chromosome 14 in nasopharyngeal carcinoma. Int J Cancer 1998, 78:153–156.
Shibosawa E, Tsutsumi K, Koizuka I, et al.: Absence of nuclear p16 from Epstein-Barr virus-associated undifferentiated nasopharyngeal carcinomas. Laryngoscope 2000, 110:93–97.
Lo KW, Cheung ST, Leung SF, et al.: Hypermethylation of the p16 gene in nasopharyngeal carcinoma. Cancer Res 1996, 56:2721–2725.
Lo KW, Huang DP, Lau KM: p16 gene alterations in nasopharyngeal carcinoma. Cancer Res 1995, 2039–2043.
Gulley ML, Nicholls JM, Schneider BG, et al.: Naso-pharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein but consistently express the retinoblastoma gene product. Am J Pathol 1998, 52:865–869.
Claudio PP, Howard CM, Fu Y, et al.: Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma. Cancer Res 2000, 60:8–12.
Lo KW, Mok CH, Huang DP, et al.: p53 mutation in human nasopharyngeal carcinomas. Anticancer Res 1992, 12:1957–1963.
Chakrani F, Armand JP, Lenoir G, et al.: Mutations clustered in exon 5 of the p53 gene in primary nasopharyngeal carcinomas from Southeastern Asia. Int J Cancer 1995, 61:316–320.
Spruck CH, Tsai YC, Huang DP, et al.: Absence of p53 gene mutations in primary nasopharyngeal carcino-mas. Cancer Res 1992, 52:4787–4790.
Van Tornout JM, Spruck CH, Shibata A, et al.:Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC. Cancer Epidemiol Biomarkers Prev 1997, 6:493–497.
Masuda M, Shinokuma A, Hirakawa N, et al.: Expres-sion of bcl-2-, p53, and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment. Head Neck 1998, 20:640–644.
Sun Y, Hegamyer G, Colburn NH: Nasopharyngeal carcinoma shows no detectable retinoblastoma susceptibility gene alterations. Oncogene 1993, 8:791–795.
Mutirangura A, Charuruks N, Shuangshoti S, et al.:Identification of distinct regions of allelic loss on chromosome 13q in nasopharyngeal cancer from paraffin embedded tissues. Int J Cancer 1999, 83:210–214.
Roychowdhury DF, Tseng AJ, Fu KK, et al.: New prog-nostic factors in nasopharyngeal carcinoma. Tumor angiogenesis and C-erbB2 expression. Cancer 1996, 77:1419–1426.
Porter MJ, Field JK, Leung SF, et al.: The detection of the c-myc and ras oncogenes in nasopharyngeal carcinoma by immunohistochemistry. Acta Otolaryngol 1994, 14:105–109.
Qian CN, Zhang CQ, Guo X, et al.: Elevation of serum vascular endothelial growth factor in male patients with metastatic nasopharyngeal carcinoma. Cancer 2000, 88:255–261.
Wakisaka N, Wen QH, Yoshizaki T, et al.: Association of vascular endothelial growth factor expression with angiogenesis and lymph node metastasis in naso-pharyngeal carcinoma. Laryngoscope 1999, 109:810–814.
Vera-Sempere FJ, Burgos JS, Botella MS, Morera C:Immunohistochemical expression of Bcl-2 onco-protein in EBV-associated nasopharyngeal carcinoma correlated to histological type and survival. Histol Histopathol 1997, 12:9–18.
Tsai ST, Jin YT, Leung HW, et al.: Bcl-2 and proliferating cell nuclear antigen (PCNA) expression correlates with subsequent local recurrence in nasopharyngeal carcinomas. Anticancer Res 1998, 18:2849–2854.
Harn HJ, Hsieh HF, Ho LI, et al.: Apoptosis in naso-pharyngeal carcinoma as related to histopathological characteristics and clinical stage. Histopathology 1998, 33:117–122.
Cheng RY, Yuen PW, Nicholls JM, et al.: Telomerase activation in nasopharyngeal carcinomas. Br J Cancer 1998, 77:456–460.
Chang JT, Liao CT, Jung SM, et al.: Telomerase activity is frequently found in metaplastic and malignant human nasopharyngeal tissues. Br J Cancer 2000, 82:1946–1951.
Huang SC: Nasopharyngeal cancer: a review of 1605 patients treated radically with cobalt 60. Int Radiat Oncol Biol Phys 1980, 6:401–407.
Huang SC, Lui LT, Lynn TC: Nasopharyngeal cancer: study III. A review of 1206 patients treated with combined modalities. Int J Radiat Oncol Biol Phys 1985, 11:1789–1793.
Lee AWM, Poon YF, Foo W, et al.: Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. Int J Oncol Biol Phys 1992, 23:261–270.
Qin D, Hu Y, Yan J, et al.: Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation. Cancer 1988, 61:1117–1124.
Wang DC, Cai WM, Hu YH, Gu XZ: Long-term survival of 1035 cases of nasopharyngeal carcinoma. Cancer 1988, 61:2338–2341.
Zhang EP, Lian PG, Cai KL, et al.: Radiation therapy of nasopharyngeal carcinoma: prognostic factors based on a 10-year follow-up of 1302 patients. Int J Radiat Oncol Biol Phys 1989, 16:301–305.
Hong S, Wu HG, Chie EK, et al.: Neoadjuvant chemo-therapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1999, 45:901–905.
Teo P, Ho JHC, Choy D, et al.: Adjunctive chemotherapy to radical radiation therapy in the treatment of advanced nasopharyngeal carcinoma. Int J Oncol Biol Phys 1987, 13:679–685.
Teo PML, Chan ATC, Lee WY, et al.: Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemo-therapy. Int J Oncol Biol Phys 1999, 43:261–271.
Al-Sarraf M, LeBlanc M, Giri S, et al.: Superiority of chemo-radiotherapy vs radiotherapy in patients with locally advanced nasopharyngeal cancer. Preliminary results of Intergroup randomized study. J Clin Oncol 1998, 16:1–9. Detailed description of the H&N Intergroup Phase III Trial 0099 for advanced nasopharyngeal carcinomas.
Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemoradio-therapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998, 4:1310–1317.
Ali H, Al-Sarraf M: Chemotherapy in advanced nasopharyngeal cancer. Oncology 2000, 8:1123–1230. Very recent review and critique of the state of the art for treat-ing patients with advanced stage nasopharyngeal carcinomas in North America and Asia.
Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated naso-pharyngeal carcinoma: a positive effect on pro-gression-free survival. International Nasopharynx Cancer Study Group. VUMCAI trial. Int J Radiat Oncol Biol Phys 1996, 35:463–469.
Chan ATC, Teo PML, Leung TWT, et al.: A prospective randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma. Int J Oncol Biol Phys 1995, 33:569–577.
Chua DTT, Sham JST, Choy D, et al.: Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma Cancer 1998, 83:2270–2283.
Tan EH, Chua ET, Wee J, et al.: Concurrent chemo-radiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results. Int J Oncol Biol Phys 1999, 45:597–601.
Rossi A, Molinari R, Boracchi P, et al.: Adjuvant chemo-therapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study. J Clin Oncol 1988, 6:1401–1410.
Chan ATC, Tao PML, Ngran RRC, et al.: A phase III randomized trial comparing concurrent chemo-therapy-radiotherapy with radiotherapy alone in local-regionally advanced nasopharyngeal carcinoma. Proc Am Soc Clin Oncol 2000, 19:415a.
Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. RTOG Study. Cancer 1987, 59:259–265.
Forastiere AA: Taxoids in head and neck cancer: the American approach. Review. Acta Otorhinolaryngol Belg 1999, 53:253–257.
Cardinali M, Jakus J, Robbins KC, et al.: P21WAF retards the growth of human squamous cell carcinomas in vivo. Eur J Cancer 1998, 34:211–218.
Massimo Cardinali F, Kratochvil J, Ensley JF, et al.:Functional characterization in vivo of mutant p53 molecules derived from squamous cell carcinomas of the head and neck. Mol Carcinog 1997, 18:78–88.
Shibuya TY, Wei WZ, Zormeier M, et al.: Anti CD3/ CD28 MoAb coated suture enhances HNSCC patients immune response. Arch Otolaryngol Head Neck Surg 1999, 125:1229–1234.
Shillitoe EJ, May M, Patel V, et al.: Genome-wide analysis of oral cancer—early results from the Cancer Genome Anatomy Project. Oral Oncol 2000, 36:8–16.
Clayman GL, Frank DK, Bruso PA, Goepfert H: Adeno-virus-mediated wild-type p53 gene transfer as a surgical adjuvant in advanced head and neck cancers. Clin Cancer Res 1999, 5:1715–1722.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ensley, J.F., Youssef, E., Kim, H. et al. Locally advanced nasopharyngeal cancer. Curr. Treat. Options in Oncol. 2, 15–23 (2001). https://doi.org/10.1007/s11864-001-0013-9
Issue Date:
DOI: https://doi.org/10.1007/s11864-001-0013-9