Nasopharyngeal carcinoma is a malignant tumor with unique features
that make it pathologically, epidemiologically, and clinically
distinct from other head and neck cancers. There is no clear
association with tobacco or alcohol use in most cases of
nasopharyngeal cancer (World Health Organization [WHO] grades II and
III). Patients with nasopharyngeal carcinoma have a higher incidence
of nodal involvement and bilateral nodal disease at presentation, and
overall (80% to 90%) nodal metastasis, as compared with patients with
other malignancies of the head and neck. In addition, patients with
nasopharyngeal carcinoma have a higher overall incidence of systemic
metastasis than patients with tumors in other head and neck sites.
In the United States and Europe, the incidence of nasopharyngeal
cancer ranges from 0.5 to 2 cases per 100,000 people. In some
areas of the world, namely, southern China, Southeast Asia, North
Africa, the Middle East, Alaska, and Greenland,[1-5] nasopharyngeal
cancer is more common. In these areas, incidence may be as high as 25
to 50 per 100,000 people, and the pathology is mostly of the
undifferentiated variety. The Epstein-Barr virus is more strongly
associated with nasopharyngeal carcinoma in areas of higher
prevalence and in patients whose tumors are WHO grades II and III
than in less aggressive grades and in areas of lower incidence.
Nasopharyngeal carcinoma affects men more often than women, with a
male-to-female ratio of 33.5:1.[1,6] The incidence of the
disease begins to rise at age 20 years and starts to decline at age
60 years, with a median age of incidence of 40 to 50 years.
Nasopharyngeal carcinomas respond to radiation therapy (Table
1[7-23]) as well as chemotherapy (Tables
2[24-38] and 3[25,28,30,39-50]).
Because nasopharyngeal cancer responds so well to radiotherapy, and
in light of the sensitive location of the primary disease and the
often advanced stage at presentation, surgery is often unnecessary or
impractical. However, for persistent or recurrent disease in regional
nodes, surgery is the treatment of choice in most cases.
Radiotherapy has been the traditional, standard form of therapy for
all patients with local and locoregional disease. Marcial et al
reported complete local clearance of nasopharyngeal carcinoma in 96%
of patients with T1 disease treated with radiotherapy, 88% of those
with T2, 81% of those with T3, and 74% of those with T4. Complete
clearance rates in patients with N1-3 disease who received
irradiation ranged from 93% to 71%. The 5-year survival rate of these
patients with nodal involvement was only 40%; overall 5-year survival
rates of patients with all stages of nasopharyngeal carcinoma treated
with radiotherapy, reported by various investigators from all over
the world, have ranged from 24% to 62% (Table
Qin et al reviewed the survival rates of 1,379 patients with
advanced nasopharyngeal carcinoma treated with radiotherapy. The
majority of patients had either stage III (n = 417) or stage IV
cancer (n = 647). These investigators reported that the 5, 10-, and
20-year survival rates of patients with stage III cancers treated
with radiotherapy alone were 46%, 29%, and 17%, respectively. The 5-,
10-, and 20-year survival rates of stage IV patients treated with
irradiation were 29%, 21%, and 8%, respectively. Overall, the 5-year
survival rate of nasopharyngeal carcinoma patients with stage IV
disease treated with radiotherapy alone was less than 30%, regardless
of country of origin or histopathology.
Locoregional recurrences occur in 40% to 80% of patients, and distant
recurrences in 15% to 50% of patients. The usual radiation dose is 65
to 75 Gy in 1.8- to 2.0-Gy fractions, 5 days a week. This dose is
crucial for achieving complete locoregional control and 5-year survival.
In a nonrandomized trial reported by Wang, the local control rate
improved significantly with accelerated hyperfractionated
radiotherapy, as compared with once-daily radiotherapy. The improved
local control rates occurred in patients with N2-3 disease and among
both males and females.
Despite the high initial response rate and good local control
achieved with radiotherapy in patients with locally advanced stage
III and IV nasopharyngeal carcinoma, the 5- and 10-year survival
rates were poor and unacceptable. Options for patients who experience
local and/or regional failure include reirradiation and,
occasionally, surgical resection; the latter is especially
appropriate for patients with involvement of regional lymph nodes
only. The majority of patients with recurrent disease, and all
patients with metastatic disease, should be treated with systemic
chemotherapy for palliation.
Nasopharyngeal carcinomas are highly sensitive to chemotherapy (Tables
2 and 3). Single agents
identified as being active in this disease include methotrexate,
bleomycin (Blenoxane), doxorubicin, cisplatin (Platinol), carboplatin
(Paraplatin), and, more recently, paclitaxel (Taxol), and to a lesser
extent, fluorouracil (5-FU) and the vinca alkaloids. For patients
with head and neck cancers in general, and especially for those with
nasopharyngeal carcinoma, combination chemotherapeutic regimens are
more active than single drugs, and cisplatin-based combinations are
more active than noncisplatin-based combinations.[24-26]
The combination most widely used in these patients is cisplatin plus
a 5-FU infusion. The regimen is easy to administer and well tolerated
by most patients. Fluorouracil is given at a dose of 1,000
mg/m²/d as a 4- to 5-day continuous infusion, and cisplatin is
given at a dose of 80 to 100 mg/m² on the first day of
treatment.[53,54] The course is repeated every 3 to 4 weeks.
Chemotherapy for Recurrent or Metastatic Disease
Patients with nasopharyngeal carcinoma who present with metastatic
disease and those whose cancers recur after initial curative
treatment and who have received further local treatment with surgery
and/or reirradiation should be treated with systemic chemotherapy for
palliative purposes. Because of the rarity of this disease,
especially in western countries, all reported chemotherapy trials for
recurrent/metastatic nasopharyngeal carcinoma are phase II studies (Table
2). Since 1980, the success of cisplatin-based combinations in
patients with head and neck cancers has made these regimens the first
choice for the treatment of nasopharyngeal carcinoma (Table
As shown in Table 2, the majority
of the cisplatin-based combinations reported consist of cisplatin
plus a 5-FU infusion, with or without other agents, such as
leucovorin or bleomycin. The overall response rate is between 50% and
65%, but, more importantly, approximately 15% to 20% of treated
patients achieve a complete response. From the phase II trial data,
it does not seem that the addition of other agents to cis-
platin5-FU infusion produces higher overall or complete
response rates. More recently, other active combinations have been
investigated using newer active agents, such as paclitaxel[35-37] and
The majority of patients who achieve a complete response to
chemotherapy remain alive for more than 2 years, or are even
considered cured. No standard duration of further treatment in
patients who have achieved a complete response has been reported. It
is our opinion that, if a biopsy confirms a complete response after
local recurrence, or a computed tomographic (CT) scan or bone scan
confirms complete response after nodal or systemic recurrence, an
additional four to six courses of chemotherapy may need to be
administered. Patients who achieve a complete response need to be
followed closely, especially for the first 2 years after completion
The important prognostic factors that may influence overall and
complete response to chemotherapy in nasopharyngeal carcinoma
patients[53,54] are performance status, histopathology (WHO grades I,
II, and III), local vs systemic disease, site of the systemic
metastasis, bulk of recurrent or metastatic cancers being treated,
type of chemotherapy combinations used, and adequacy of treatment given.
Chemotherapy as Part of Combined-Modality Treatment for Primary Disease
Because of the high incidence of locoregional failure with
radiotherapy alone despite the initial high clearance rate, and
because of the high incidence of distant metastasis in nasopharyngeal
cancers, combined-modality therapy is a very attractive concept.
Chemotherapy can be given neoadjuvantly (induction chemotherapy
followed by radiation), concomitantly, or adjuvantly (radiotherapy
followed by chemotherapy). The use of more than one of these
approaches in sequence has also been investigated.
Neoadjuvant (Induction) ChemotherapyNeoadjuvant
chemotherapy was explored in the mid-1970s in patients with locally
advanced stage III and IV head and neck cancers of all sites. Most of
these patients, including those with nasopharyngeal carcinomas, had
inoperable or unresectable disease. High overall and clinical
complete response rates to induction chemotherapy were obtained, and
the feasibility of sequential induction chemotherapy followed by
radiotherapy was established. This led to many phase II studies using
the same treatments in patients with locally advanced nasopharyngeal
cancers (Table 3).
The factors that may influence response rate and overall survival are
stage of the nasopharyngeal carcinoma (especially the N stage),
performance status, histopathology, type of chemotherapeutic
combination used, number of courses, and adequacy of treatment given.
In addition, reports of complete response at the primary site may
differ from investigator to investigator, depending on whether the
response was evaluated clinically, by CT scan, or by magnetic
resonance imaging (MRI). Since the majority of patients initially
present with T3 or T4 disease, some abnormalities may still be
observed locally when a CT scan or MRI is performed; this can occur
even in patients who have repeated negative biopsies of these areas
and are considered cured without further treatment. Factors that may
affect survival are disease stage, type of response to chemotherapy
(partial vs complete), histopathology, and performance status.
The majority of the neoadjuvant chemotherapy trials mentioned here
used cisplatin-based combinations, especially cisplatin plus a 5-FU
infusion. In a few trials, leucovorin or bleomycin was added to this
combination. These studies demonstrated interesting results, with
overall response rates of 80% to 90%. In some trials, up to 66% of
the responses were complete. Because of the various prognostic
factors that may influence response rate, no determination could be
made as to the best possible chemotherapy combination.
Geara et al and Teo et al reported much higher complete
response rates to chemotherapy for nodal disease than for primary
tumors. Both these investigators used CT scans to evaluate responses.
In our experience, both in patients with nasopharyngeal carcinoma and
in patients with other head and neck cancers treated with
chemotherapy, the complete response rate is usually higher at the
primary site than the regional lymph nodes.
When the survival of patients treated with chemotherapy followed by
irradiation was compared to historical matched controls receiving
radiotherapy alone, the majority of investigators reported
significant improvement in overall survival for the combined
approach. This was especially true for the administration of adequate
doses of two to three courses of cisplatin and 5-FU infusion.
Recently, Teo et al reported on the results of two courses of
cisplatin and 5-FU infusion followed by radiotherapy in 209 patients
with node-positive, locally advanced nasopharyngeal cancers, compared
to similar patients treated with radiotherapy alone during the same
period. The chemotherapy group had significantly more bulky nodes,
lower cervical and/or supraclavicular nodes, and more advanced
overall stages than the nonchemotherapy patients. Unfortunately, the
duration of the 5-FU infusion was 3 days, instead of the standard 5
days, and only two courses of chemotherapy were given instead of the
usual three courses.
Despite these facts, the addition of chemotherapy to radiation
treatment significantly enhanced local control in node-positive
nasopharyngeal cancer patients in general, and node-positive, T3 and
T4, stage IV patients in particular. The 5-year survival rate among
patients with stage IV cancers ranged from 50% to 55% in those who
underwent sequential radiotherapy, as compared to less than 30% in
those who received radiotherapy only. When evaluating survival in
patients with nasopharyngeal carcinoma, a minimum follow-up of 3
years is necessary before any conclusions can be drawn.
Concomitant ChemoradiotherapyThis option is
attractive, with the possible advantages of synergy between
chemotherapy and radiotherapy, as well as additive effects.
Chemoradiotherapy has been investigated in many other solid
malignancies; improved disease-free and overall survival rates have
been reported for the combined approach, as opposed to radiotherapy alone.
Many phase II trials of concurrent chemoradiotherapy in patients with
locally advanced nasopharyngeal carcinoma have been reported.[55-65]
Several chemotherapeutic agents, especially cisplatin,[67-69] produce
synergistic and/or additive effects when used with radiotherapy. One
possible advantage of using concomitant cisplatin and radiotherapy in
patients with head and neck cancers, as opposed to other agents, such
as methotrexate, bleomycin, or 5-FU, is the lack of increased local
side effects (especially mucositis).
Most investigators gave standard one-fraction-per-day irradiation.
The radiation dose was the same as without chemotherapy, ie, >
6,400 cGy in most cases. When the results of concomitant
chemoradiotherapy were compared with those of historical matched
control patients, most investigators reported improvements in local
control, disease-free survival, and overall survival with the
Other agents, such as the taxanes and gemcitabine (Gemzar), have been
shown to be radiation sensitizers and/or enhancers. These agents,
administered concomitantly with radiotherapy, may need to be
investigated in the future in patients with nasopharyngeal carcinoma.
In an early study published by the Radiation Therapy Oncology Group
(RTOG),[64-66] we reported the results of concomitant treatment with
single-agent cisplatin and radiotherapy in 124 patients with locally
advanced, inoperable or unresectable stage III (n = 24) or stage IV
(n = 100) head and neck cancers; this study population included 28
patients with nasopharyngeal cancers, 27 of whom had stage IV
disease. The cisplatin dose was 100 mg/m2, given intravenously with
hydration and mannitol diuresis, once every 3 weeks, concurrent with
standard radiation therapy to a total dose of up to 7,380 cGy.
Complete response rates were 70% for all patients and 89% for those
with nasopharyngeal cancers.
When the survival of patients with nasopharyngeal cancer was compared
with survival of those with tumors of other head and neck sites (all
were treated with the same chemoradiotherapy), a significantly higher
survival rate was observed in the nasopharyngeal carcinoma patients.
In addition, the survival of the nasopharyngeal carcinoma patients
treated with concurrent cisplatin and radiotherapy was significantly
better than the survival of historical matched controls treated with
the same dose of radiotherapy alone.
Even more interesting was the fact that approximately 55% of the
patients with cancers of the nasopharynx who had received
chemoradiotherapy were still alive 5 years later. No additive local
toxicities were observed with chemoradiotherapy when compared to
matched historical control patients with head and neck cancers
treated with the same dose of radiotherapy alone.
Adjuvant ChemotherapyIn patients with locally
advanced nasopharyngeal carcinoma, the administration of systemic
chemotherapy after radiotherapy may help to consolidate the local
control achieved with radiation and reduce the incidence of
microscopic systemic metastasis. These beneficial effects of adjuvant
chemotherapy may result in improved disease-free and overall survival.
A prospective, randomized trial of radiotherapy followed by
vincristine, cyclophosphamide (Cytoxan, Neosar), and doxorubicin that
did not show any benefit from the use of adjuvant chemotherapy is
discussed below. In another phase II trial, the combination
chemotherapy used (5-FU and cisplatin) was too toxic, resulting in
high treatment-related mortality.
Other reports[72-76] of single-arm studies, however, did show
possible benefits of adjuvant chemotherapy in patients with
nasopharyngeal carcinoma. Many newer agents, and combinations
thereof, may have fewer local mucosal side effects; these may need to
be investigated in the future.
1. Fandi A, Altun M, Azli N, et al: Nasopharyngeal cancer,
epidemiology, staging and treatment. Semin Oncol 21: 382-397, 1994.
2. Ho JHC: An epidemiological and clinical study of nasopharyngeal
carcinoma. Int J Radiat Oncol Biol Phys 4:183-197, 1978.
3. Flores AD, Dickson RI, Riding K, et al: Cancer of the nasopharynx
in British Columbia. Am J Clin Oncol 9:281-291, 1986.
4. Forastiere A, Goepfert H, Goffinet D, et al: NCCN practice
guidelines for head and neck cancer. Oncology 12(7A):134-139, 1998.
5. Sham JST, Cheung YK, Choy D, et al: Computed tomography evaluation
of neck node metastases from nasopharyngeal carcinoma. Int J Radiat
Oncol Biol Phys 26:787-792, 1993.
6. Chan A, Teo P, Leung T, et al: The role of chemotherapy in the
management of nasopharyngeal carcinoma. Cancer 82:1002-1012, 1998.
7. Meyer JE, Wang CC: Carcinoma of the nasopharynx: Factors
influencing results of therapy. Radiology 100:385-388, 1971.
8. Moench HC, Phillips TL: Carcinoma of the nasopharynx: Review of
146 patients with emphasis on radiation dose and time factors. Am J
Surg 124:515-518, 1972.
9. Hoppe RT, Goffinet OR, Bagshaw MA: Carcinoma of the nasopharynx:
Eighteen years experience with megavoltage. Cancer 37:2605-2612, 1976.
10. Baker S: Nasopharyngeal carcinoma: Clinical course and results of
therapy. Head Neck Surg 3:8-14, 1980.
11. Shu-Chen H: Nasopharyngeal cancer: A review of 1605 patients
treated radically with cobalt 60. Int J Radiat Oncol Biol Phys
12. Marcial VA, Hanley JA, Chang C, et al: Split-course radiation
therapy of carcinoma of the nasopharynx: Results of a national
collaborative clinical trial of the Radiation Therapy Oncology Group.
Int J Radiat Oncol Biol Phys 6:409-414, 1980.
13. Mesic JB, Fletcher GH, Goepfert H, Megavoltage irradiation of
epithelial tumors of the nasopharynx. Int J Radiat Oncol Biol Phys
14. Applebaum EL, Mantravadi P, Haas R, Lymphoepithelioma of the
nasopharynx. Laryngoscope 92:510-514, 1982.
15. Hsu MM, Huang SC, Lynn TC, et al: The survival of patients with
nasopharyngeal carcinomas. Otolaryngol Head Neck Surg 90:289-295, 1982.
16. Vikram B, Strong EW, Manolatoss S, et al: Improved survival in
carcinoma of the nasopharynx. Head Neck Surg 7:123-128, 1984.
17. Rahima M, Rakowsky E, Barzilay J, et al: Carcinoma of the
nasopharynx: An analysis of 91 cases and a comparison of different
treatment approaches. Cancer 58:843-849, 1986.
18. Qin D, Hu Y, Yan J, et al: Analysis of 1379 patients with
nasopharyngeal carcinoma treated by radiation. Cancer 61:1117-1124, 1988.
19. Wang DC, Cai WM, Hu VC, et al: Long-term survival of 1035 cases
of nasopharyngeal carcinoma. Cancer 61:2338-2341, 1988.
20. Laramore GE, Clubb B, Quick C: Nasopharyngeal carcinoma in Saudi
Arabia: A retrospective study of 166 cases treated with curative
intent. Int J Radiat Oncol Biol Phys 15:1119-1127, 1988.
21. Bailet JW, Mark RJ, Abemayor E, et al: Nasopharyngeal
carcinoma:Treatment results with primary radiation therapy.
Laryngoscope 102:965-972, 1992.
22. Sutton JB, Green JP, Meyer JL, et al: Naopharyngeal carcinoma: A
study examining Asian patients treated in the United States. Am J
Clin Oncol 18:337-342, 1995.
23. Sanguineti G, Geara FB, Garden AS, et al: Carcinoma of the
nasopharynx treated by radiotherapy alone: Determinants of local and
regional control. Int J Radiat Oncol Biol Phys 37:985-996, 1997.
24. Decker DA, Drelichman A, Al-Sarraf M, et al: Chemotherapy for
nasopharyngeal cancer: A ten year experience. Cancer 52:602-605, 1983.
25. Al-Kourainy K, Crissman J, Ensley J, et al: Excellent response to
cisplatin based chemotherapy in patients with recurrent or previously
untreated advanced nasopharyngeal carcinoma. Am J Clin Oncol
26. Choo R, Tannock I: Chemotherapy for recurrent and metastatic
carcinoma of the nasopharynx: The Princess Margaret hospital
experience. Cancer 68:2120-2124, 1991.
27. Mahjoubi R, Azli N, Bachouchi M, et al: Metastatic
undifferentiated carcinoma of the nasopharynx treated with bleomycin,
epirubicin, cisplatin: Final report (abstract 772). Proc Am Soc Clin
Oncol 11:240, 1992.
28. Siu LL, Czaykowski PM, Tannock I: Phase I/II study of the CAPABLE
regimen for patients with poorly differentiated carcinoma of the
nasopharynx J Clin Oncol 16:2514-2521, 1998.
29. Marchini S, Licitra L, Grandi L, et al: Cisplatin and
fluorouracil in recurrent and or disseminated nasopharyngeal cancer
(abstract). Proc Am Soc Clin Oncol 10:202, 1991.
30. Chi KH, Chan WK, Cooper DL, et al: A phase II study of outpatient
chemotherapy with cisplatin, 5-fluorouracil, and leucovorin in
nasopharyngeal carcinoma. Cancer 73:247-252, 1994.
31. Yeo W, Leung TWT, Leung SF, et al: Phase II study of combination
carboplatin and 5-fluorouracil in metastatic nasopharyngeal
carcinoma. Cancer Chemother Pharmacol 38:466-470, 1996.
32. Su WC, Chen TY, Kao RH, et al: Chemotherapy with cisplatin and
continuous infusion of 5-fluorouracil and bleomycin for recurrent and
metastatic nasopharyngeal carcinoma in Taiwan. Oncology (Basel)
33. Boussen H, Cvitrovic E, Wendling JL: Chemotherapy of metastatic
and /or recurrent undifferentiated nasopharyngeal carcinoma with
cisplatin , bleomycin and fluorouracil. J Clin Oncol 9:1675-1681, 1991.
34. Cvitkovic E, Mahjoubi R Lianes P: Fluorouracil, mitomycin
,epirubicin, cisplatin in recurrent and/or metastatic
undifferentiated nasopharyngeal carcinoma (UCNT) (abstract). Proc Am
Soc Clin Oncol 10:200, 1991.
35. Tan EH, Khoo KS, Wee J, et al: Phase II trial of paclitaxel and
carboplatin combination in Asian patients with metastatic
nasopharyngeal carcinoma. Ann Oncol 10:235-237, 1999.
36. Fountzilas G, Skarlos D, Athanassiades A, et al: Paclitaxel by
three-hour infusion and carboplatin in advanced carcinoma of the
nasopharynx and other sites of the head and neck. A phase II study
conducted by the Hellenic Cooperative Oncology Group. Ann Oncol
37. Yeo W, Leung TW, Chan AT: A phase II study of combination
paclitaxel and carboplatin in advanced nasopharyngeal carcinoma Eur J
Cancer 34:2027-2031, 1998.
38. Stein ME, Ruff P, Weaving A, et al: A phase II study of
cisplatin/ifosfamide in recurrent/metastatic undifferentiated
nasopharyngeal carcinoma among young blacks in southern Africa. Am J
Clin Oncol 19:386-388, 1996.
39. Galligioni E, Carbone A, Tirelli U, et al: Combined chemotherapy
with doxorubicin, bleomycin, vinblastine, dacarbazine, and
radiotherapy for advanced lymphoepithelioma. Cancer Treat Rep
40. Tannock I, Payne D, Cummings B, et al: Sequential chemotherapy
and radiation for nasopharyngeal cancer: Absence of long-term benefit
despite a high rate of tumor response to chemotherapy. J Clin Oncol
41. Garden AS, Lippman SM, Morrison WH, et al: Does induction
chemotherapy have a role in the management of nasopharyngeal
carcinoma? Results of treatment in the era of computerized
tomography. Int J Radiat Oncol Biol Phys 5:1005-1012, 1996.
42. Clark JR, Norris CM, Dreyfuss AI, et al: Nasopharyngeal
carcinoma: The Dana-Farber Cancer Institute experience with 24
patients treated with induction chemotherapy and radiotherapy. Ann
Otol Rhinol Laryngol 96:608-614, 1987.
43. Bachouchi M, Cvitkovic E, Azli N, et al: High complete response
in advanced nasopharyngeal carcinoma with bleomycin, epirubicin, and
cisplatin before radiotherapy. J Int Cancer Inst 82:616-620, 1990.
44. Azli N, Bachouchi M, Chadjaa M, et al: Update on treatment of
locally advanced undifferentiated carcinoma of nasopharyngeal type
(UNCT). Proceedings of the Fourth International Symposium,
Interaction of Chemotherapy and Radiotherapy, p 28. Toronto, Canada, 1992.
45. Dimery IW, Peters LJ, Goepfert H, et al: Effectiveness of
combined induction chemotherapy in advanced nasopharyngeal carcinoma.
J Clin Oncol 11:1919-1928, 1993.
46. Geara F, Glisson BS, Sanguineti G, et al: Induction chemotherapy
followed by radiotherapy vs radiotherapy alone in patients with
advanced nasopharyngeal carcinoma. Cancer 79:1279-1286, 1997.
47. Zidan J, Kuten A, Robinson E: Intensive short course chemotherapy
followed by radiotherapy of locally advanced nasopharyngeal
carcinoma. Cancer 77:1973-1977, 1996.
48. Teo, PML, Chan ATC, Lee WY, et al: Enhancement of local control
in locally advanced node-positive nasopharyngeal carcinoma by
adjunctive chemotherapy. Int J Radiat Oncol Biol Phys 43:261-271, 1999.
49. Onat H, Altun M, Bilge N, et al: Chemotherapy and radiotherapy
for locally advanced undifferentiated nasopharyngeal carcinoma.
Proceedings of the Fourth International Symposium, Interaction of
Chemotherapy and Radiotherapy, p 31. Toronto, Canada, 1992.
50. Azli N, Armand JP, Rahal M, et al: Alternating chemo-radiotherapy
with cisplatin and 5-fluorouracil plus bleomycin by continuous
infusion for locally advanced undifferentiated carcinoma
nasopharyngeal type. Eur J Cancer 28A:1792-1797, 1992.
51. Wang CC: Accelerated hyperfractionation radiation therapy for
carcinoma of the nasopharynx. Cancer 63:2461-2467, 1989.
52. Teo PM, Kwan WH, Chan AT, et al: How successful is high-dose
(³ 60 Gy) reirradiation using mainly external beams in salvaging
local failures of nasopharyngeal carcinoma? Int J Radiat Oncol Biol
Phys 40:897-913, 1998.
53. Al-Sarraf M: Chemotherapeutic management of head and neck cancer.
Cancer Metastasis Rev 6:181-198, 1987.
54. Al-Sarraf M: Head and neck cancer: Chemotherapy concepts. Semin
Oncol 15:70-85, 1988.
55. Richards GJ, Chambers RG: Hydroxyurea in the treatment of
neoplasm of the head and neck. Am J Surg 126:513-518, 1973.
56. Van Andel JG, Hop WJC: Carcinoma of the nasopharynx: Review of 86
cases. Clin Radiol 33:95-99, 1982.
57. Huang SC, Tak Lui L, Lynn TS: Nasopharyngeal cancer: Study III. A
review of 1206 patients treated with combined modalities. Int J
Radiat Oncol Biol Phys 11:1789-1793, 1985.
58. Flores A, Dickson RI, Riding K, et al: Cancer of the nasopharynx
in British Columbia. Am J Clin Oncol 9:281-291, 1986.
59. Souhami L, Babinowits M: Combined treatment in carcinoma of the
nasopharynx. Laryngoscope 98:881-883, 1988.
60. Choi KN, Rotman M, Aziz H, et al: Concomitant infusion cisplatin
and hyperfractionated radiotherapy for locally advanced
nasopharyngeal and paranasal sinus tumors. Int J Radiat Oncol Biol
Phys 39:823-839, 1997.
61. Pendjer I, Krejovic B, Vucicevic S: A comparative study of
undifferentiated nasopharyngeal carcinoma treated with radiotherapy
or combined treatment with zorubicin-cisplatin and radiotherapy. Arch
Ororhinolaryngol 1 (suppl):127-129, 1997.
62. Maoleekoonpairoj S, Pharomratanapongse P, Puttanuparp S: Phase II
study: Concurrent chemoradiotherapy in advanced nasopharyngeal
carcinoma. J Med Assoc Thailand 80:778-784, 1997.
63. Lin JC, Chen KY, Jan JS, et al: Partially hyperfractionated
accelerated radiotherapy and concurrent chemotherapy for advanced
nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 36:1127-1136, 1996.
64. Al-Sarraf M, Zundmanis M, Marcial V, et al: Concurrent cisplatin
and radiotherapy in patients with locally advanced nasopharyngeal
carcinoma. RTOG study (abstract). Proc Am Soc Clin Oncol 5:142, 1986.
65. 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 59:259-265, 1987.
66. Al-Sarraf M, Pajak TF, Cooper JS, et al: Chemo-radiotherapy in
patients with locally advanced nasopharyngeal carcinoma: A Radiation
Therapy Oncology Group study. J Clin Oncol 8:1342-1351, 1990.
67. Douple EB, Richmond RC, Logan ME: Therapeutic potentiation in a
mouse mammary tumor and an intracerebral rat brain tumor by combined
treatment with cis-dichlorodiammineplatinum (II) and radiation. J
Clin Hematol Oncol 7:585-603, 1977.
68. Soloway MS, Morris CR, Sudderth B: Radiation therapy and
cis-dichlorodiammineplatinum (II) in transplantable and primary
murine bladder cancer. Int J Radiat Oncol Biol Phys 5:1355-1360, 1979.
69. Szumiel I, Nias AHW: The effect of combined treatment with a
platinum complex and ionizing radiation on Chinese hamster ovary
cells in vitro. Br J Cancer 33:450-458, 1976.
70. Rossi A, Molinari R, Boracchi P, et al: Adjuvant chemotherapy
with vincristine, cyclophosphamide, and doxorubicin after
radiotherapy in local-regional nasopharyngeal cancer: Results of a
4-year multicenter randomized study. J Clin Oncol 6:1401-1410, 1988.
71. Lin JC, Jan JS, Hsu CY: Preliminary report of outpatient weekly
adjuvant chemotherapy for high-risk nasopharyngeal carcinoma. Am J
Clin Oncol 19:624-627, 1996.
72. Roper HP, Essex-Carter A, Marsden HB, et al: Nasopharyngeal
carcinoma in children. Pediat Hematol Oncol 3:143-152, 1986.
73. Rahima M, Rakowsky E, Barzilay J, et al: Carcinoma of the
nasopharynx An analysis of 91 cases and a comparison of different
treatment approaches. Cancer 58:843-849, 1986.
74. Tsuji H, Kamada T, Tsuji H, et al: Improved results in the
treatment of nasopharyngeal carcinoma using combined radiotherapy and
chemotherapy. Cancer 63:1668-1672, 1989.
75. Droz JP, Domenge C, Marin JL, et al: Adjuvant chemotherapy of
regionally advanced UCNT with monthly vindesine, adriamycin,
bleomycin, cyclophosphamide and cisplatin: Increasing disease free
survival (abstract). Proc Am Soc Clin Oncol 6:545, 1987.
76. Kim TH, McLaren J, Alvarado CS, et al: Adjuvant chemotherapy for
advanced nasopharyngeal carcinoma in childhood. Cancer 63:1922-1926, 1989.
77. Cvitkovic E, Grange GRL, Temple S: Neoadjuvant chemotherapy with
epirubicin, cisplatin, bleomycin in undifferentiated nasopharyngeal
cancer: Preliminary results of an international phase III trial
(abstract). Proc Am Soc Clin Oncol 13:283, 1994.
78. Chan TC, Teo PML, Leung TWT, et al: Prospective randomized trial
conducted to compare chemoradiotherapy against radiotherapy alone in
the treatment of locoregionally advanced nasopharyngeal carcinoma.
Int J Radiat Oncol Biol Phys 33:560-577, 1995.
79. International Nasopharyngeal Cancer Study Group: Preliminary
results of the randomized trial comparing neoadjuvant chemotherapy
(cisplatinum, epirubicin, bleomycin) plus radiotherapy vs
radiotherapy alone in stage IV (³ N2, M0) undifferentiated
nasopharyngeal cancer. Int J Radiat Oncol Biol Phys 35:463-469, 1996.
80. El-Guedari B: Final results of the VUMCA 1 randomized trial
comparing neoadjuvant chemotherapy plus radiotherapy to RT alone in
undifferentiated nasopharyngeal carcinoma (abstract). Proc Am Soc
Clin Oncol 17:385a, 1998.
81. 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 vs
radiotherapy alone in the treatment of patients with locoregionally
advanced nasopharyngeal carcinoma. Cancer 83:2270-2283, 1998.
82. Al-Sarraf M, LeBlanc M, Giri PGS, et al: Chemoradiotherapy vs
radiotherapy in patients with advanced nasopharyngeal cancer: Phase
III randomized Intergroup study 0099. J Clin Oncol 16:1310-1317, 1998.
83. Al-Sarraf M, LeBlanc M, Giri PGS, et al: Chemo-radiotherapy vs
radiotherapy in patients with advanced nasopharyngeal cancer:
Intergroup (0099) SWOG 8892 , RTOG 8817, ECOG 2388, progress report
(abstract). Proc Am Soc Clin Oncol 17:385a, 1998.