Resectable Oropharyngeal Cancer
Unresectable Oropharyngeal Cancer
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The management of stage IV carcinomas of the oropharynx is complex and requires multidisciplinary input to establish the optimal treatment. New surgical techniques for resection and reconstruction developed in the last 7 to 10 years that provide access and at least partial function restoration have extended the surgical options. External-beam radiation therapy augmented with interstitial implantation and multiple daily treatment schemes have given new insights into the use of radiation for this group of tumors.[1] All of these patients may be considered for entry into neoadjuvant chemotherapy trials.

In general, the preferred treatment, as evidenced in RTOG-7303, for example, has been to combine surgery with postoperative radiation therapy when possible.[2] This approach has become the standard in this specific grouping whenever it can be applied. Patients with stage IVA cancer of the tonsil treated by aggressive radiation therapy alone have similar results to patients treated with combination therapy.[3][Level of evidence: 3iiiDiii]

Specific surgical procedures and their modifications are not designated here because of the wide variety of surgical approaches to the area, the variety of opinions about the role of modified neck dissections, and the multiple reconstructive techniques that may give the same results. This group of patients should be managed by surgeons who are skilled in the multiple procedures available and actively and frequently involved in the care of these patients.

Standard treatment options:

1. A combination of surgery with postoperative radiation therapy plus chemotherapy in high-risk patients.[2]



2. Radiation therapy alone for patients with stage IVA cancer of the tonsil that does not deeply invade the tongue base.[3,4]

Treatment options under clinical evaluation:

1. Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.[5-10] The best chemotherapy to use and the appropriate way to integrate the two modalities are still unresolved.[11,12]

   Similar approaches in patients with resectable disease, when resection would lead to a major functional deficit, are also being explored in randomized trials.[13] A trial has shown that chemotherapy (i.e., carboplatin plus fluorouracil) with radiation therapy provides better local control and improved 3-year actuarial overall survival (OS) and disease-free survival than daily radiation therapy alone.[14,15]

   A meta-analysis of 63 randomized prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy.[16][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data, however, were not available; no standard regimen existed; and, the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oropharyngeal cancer.

2. Radiation clinical trials such as RTOG-8313, for example, evaluating hyperfractionation schedules and/or brachytherapy should be considered.[17] One trial has shown a higher local control rate with very accelerated radiation therapy, but the OS was not improved with this approach.[18][Level of evidence: 1iiA]

Standard treatment options:

• These patients are candidates for radiation therapy or chemoradiation therapy.[14,19,20]

Treatment options under clinical evaluation:

Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors and thereby render them more definitively treatable with either surgery or radiation. Many drug combinations have been used in neoadjuvant chemotherapy.[21-26]

1. Concomitant chemotherapy, i.e., chemotherapy with radiation clinical trials as well as with radiosensitizers.[7]



2. Radiation clinical trials evaluating hyperfractionation schedules and/or brachytherapy should be considered.[17]



3. Simultaneous chemotherapy and hyperfractionated radiation therapy.[27]



4. Particle-beam radiation therapy.



5. Hyperthermia combined with radiation therapy.

Posttreatment follow-up:

• These patients should have a careful head and neck examination to look for recurrence monthly for the first posttreatment year, every 2 months for the second year, every 3 months for the third year, and every 6 months thereafter.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV oropharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Puthawala AA, Syed AM, Eads DL, et al.: Limited external beam and interstitial 192iridium irradiation in the treatment of carcinoma of the base of the tongue: a ten year experience. Int J Radiat Oncol Biol Phys 14 (5): 839-48, 1988.  [PUBMED Abstract]
   
   
2. Tupchong L, Scott CB, Blitzer PH, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys 20 (1): 21-8, 1991.  [PUBMED Abstract]
   
   
3. Mendenhall WM, Amdur RJ, Stringer SP, et al.: Radiation therapy for squamous cell carcinoma of the tonsillar region: a preferred alternative to surgery? J Clin Oncol 18 (11): 2219-25, 2000.  [PUBMED Abstract]
   
   
4. Mendenhall WM, Morris CG, Amdur RJ, et al.: Definitive radiotherapy for squamous cell carcinoma of the base of tongue. Am J Clin Oncol 29 (1): 32-9, 2006.  [PUBMED Abstract]
   
   
5. Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.  [PUBMED Abstract]
   
   
6. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.  [PUBMED Abstract]
   
   
7. 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. An RTOG Study. Cancer 59 (2): 259-65, 1987.  [PUBMED Abstract]
   
   
8. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.  [PUBMED Abstract]
   
   
9. Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.  [PUBMED Abstract]
   
   
10. Jeremic B, Shibamoto Y, Stanisavljevic B, et al.: Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiother Oncol 43 (1): 29-37, 1997.  [PUBMED Abstract]
    
    
11. Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.  [PUBMED Abstract]
    
    
12. Zakotnik B, Smid L, Budihna M, et al.: Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report. Int J Radiat Oncol Biol Phys 41 (5): 1121-7, 1998.  [PUBMED Abstract]
    
    
13. Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000.  [PUBMED Abstract]
    
    
14. Denis F, Garaud P, Bardet E, et al.: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22 (1): 69-76, 2004.  [PUBMED Abstract]
    
    
15. Semrau R, Mueller RP, Stuetzer H, et al.: Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 64 (5): 1308-16, 2006.  [PUBMED Abstract]
    
    
16. Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.  [PUBMED Abstract]
    
    
17. Cox JD, Pajak TF, Marcial VA, et al.: Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of radiation therapy oncology group protocol 83-13. Int J Radiat Oncol Biol Phys 18 (3): 515-21, 1990.  [PUBMED Abstract]
    
    
18. Bourhis J, Lapeyre M, Tortochaux J, et al.: Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol 24 (18): 2873-8, 2006.  [PUBMED Abstract]
    
    
19. Olmi P, Crispino S, Fallai C, et al.: Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy--a multicenter randomized trial. Int J Radiat Oncol Biol Phys 55 (1): 78-92, 2003.  [PUBMED Abstract]
    
    
20. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004.  [PUBMED Abstract]
    
    
21. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987.  [PUBMED Abstract]
    
    
22. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Semin Oncol 21 (3): 349-58, 1994.  [PUBMED Abstract]
    
    
23. Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57 (4): 711-7, 1986.  [PUBMED Abstract]
    
    
24. Pfister DG, Harrison LB, Strong EW, et al.: Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation. J Clin Oncol 13 (3): 671-80, 1995.  [PUBMED Abstract]
    
    
25. Dimery IW, Hong WK: Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst 85 (2): 95-111, 1993.  [PUBMED Abstract]
    
    
26. Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000.  [PUBMED Abstract]
    
    
27. Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 118 (8): 806-10, 1992.  [PUBMED Abstract]
    
    

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