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Laryngeal Cancer Treatment (PDQ®)

  • Last Modified: 04/15/2014

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Stage IV Laryngeal Cancer

Supraglottis
Glottis
Subglottis
Current Clinical Trials



Supraglottis

Standard treatment options:

  1. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease, including those with nonbulky T4a disease.[1]

  2. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[2-7]

  3. Definitive radiation therapy alone in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[8]

  4. For patients with bulky T4 disease, surgery with postoperative radiation therapy with or without concomitant chemotherapy based on pathological adverse features.[9]

Treatment options under clinical evaluation:

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[10,11]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[12-16]

    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.[17] 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.[18]
Glottis

Standard treatment options:

  1. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease, including those with nonbulky T4a disease.[1]

  2. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[2-7]

  3. Definitive radiation therapy alone in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[8]

  4. For patients with bulky T4 disease, total laryngectomy with postoperative radiation therapy with or without concomitant chemotherapy based on pathological adverse features.[9]

Treatment options under clinical evaluation:

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[10,11]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[12,13,15,16]

    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.[17] 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.[18]
Subglottis

Standard treatment options:

  1. Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node dissection usually followed by postoperative radiation therapy.[10,19-22]
  2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery.

Treatment options under clinical evaluation:

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[10,11]
  2. Simultaneous chemotherapy and hyperfractionated radiation therapy.[23]
  3. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[12,13,15,16]

    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.[17] 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.

  4. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18]
Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV 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. Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013.  [PUBMED Abstract]

  2. 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]

  3. 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]

  4. 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]

  5. 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]

  6. 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]

  7. 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]

  8. 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]

  9. Bernier J, Cooper JS: Chemoradiation after surgery for high-risk head and neck cancer patients: how strong is the evidence? Oncologist 10 (3): 215-24, 2005.  [PUBMED Abstract]

  10. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. 

  11. 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]

  12. 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]

  13. 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]

  14. 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]

  15. 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]

  16. 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]

  17. 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]

  18. 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]

  19. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80. 

  20. Chepeha DR, Haxer MJ, Lyden T: Rehabilitation after treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 781-8. 

  21. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999. 

  22. 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]

  23. 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]