Supraglottis
Glottis
Subglottis
Current Clinical Trials

Supraglottis

Standard treatment options:

1. Surgery with or without postoperative radiation therapy, as evidenced in RTOG-7303, for example.[1-6]
2. Definitive radiation therapy with surgery for salvage of radiation failures.[7]
3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[8-13]

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[14,15]
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16-20]

   A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil (5-FU), followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

3. Isotretinoin (i.e., 13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Standard treatment options:

1. Surgery with or without postoperative radiation therapy, as evidenced in RTOG-7303, for example.[1-6,23]
2. Definitive radiation therapy with surgery for salvage of radiation failures.[7,24]
3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[8-13]

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[14,15]
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation therapy.[16,17,19,20]

   A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Standard treatment options:

1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node dissection usually followed by postoperative radiation therapy.[1-3]
2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery. Patients should be closely followed, and surgical salvage should be planned for recurrences that are local or in the neck.

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[14,15]
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16,17,19,20]

   A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III laryngeal 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. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999. 
   
   
2. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732. 
   
   
3. Arriagada R, Eschwege F, Cachin Y, et al.: The value of combining radiotherapy with surgery in the treatment of hypopharyngeal and laryngeal cancers. Cancer 51 (10): 1819-25, 1983.  [PUBMED Abstract]
   
   
4. Spaulding CA, Krochak RJ, Hahn SS, et al.: Radiotherapeutic management of cancer of the supraglottis. Cancer 57 (7): 1292-8, 1986.  [PUBMED Abstract]
   
   
5. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975.  [PUBMED Abstract]
   
   
6. 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]
   
   
7. MacKenzie RG, Franssen E, Balogh JM, et al.: Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 47 (1): 65-71, 2000.  [PUBMED Abstract]
   
   
8. Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 12 (8): 1592-9, 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. Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997.  [PUBMED Abstract]
    
    
11. 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]
    
    
12. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003.  [PUBMED Abstract]
    
    
13. 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]
    
    
14. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. 
    
    
15. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14 (4): 649-58, 1988.  [PUBMED Abstract]
    
    
16. 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]
    
    
17. 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]
    
    
18. Wang CC, Suit HD, Blitzer PH: Twice-a-day radiation therapy for supraglottic carcinoma. Int J Radiat Oncol Biol Phys 12 (1): 3-7, 1986.  [PUBMED Abstract]
    
    
19. 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]
    
    
20. 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]
    
    
21. 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]
    
    
22. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.  [PUBMED Abstract]
    
    
23. Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984.  [PUBMED Abstract]
    
    
24. Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx. Am J Clin Oncol 21 (3): 302-5, 1998.  [PUBMED Abstract]
    
    

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