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Lip and Oral Cavity Cancer Treatment (Professional) (cont.)

Stage IV Lip and Oral Cavity Cancer

Randomized, prospective trials have yet to demonstrate a benefit in either disease-free survival or overall survival for patients receiving neoadjuvant chemotherapy.[1] The use of isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primaries is under clinical evaluation.[2]

Advanced Lesions of the Lip

These lesions, including those involving bone, nerves, and lymph nodes, generally require a combination of surgery and radiation therapy.

Standard treatment options:

  1. Surgery using a variety of surgical approaches, the choice of which is dependent on the size and location of the lesion and the needs for reconstruction. Treatment of both sides of the neck is indicated for selected patients.
  2. Radiation therapy using a variety of therapy techniques, including external-beam radiation therapy (EBRT) with or without brachytherapy, the choice of which is dictated by the size and location of the lesion.

Treatment option under clinical evaluation:

  • Superfractionated radiation therapy.[3]

Advanced Lesions of the Anterior Tongue

Standard treatment options:

  1. Combined surgery (i.e., total glossectomy, sometimes requiring laryngectomy) possibly followed by postoperative radiation therapy may be used to treat selected patients.[4]
  2. Palliative radiation therapy may be used to treat patients with very advanced lesions.

Advanced Lesions of the Buccal Mucosa

Standard treatment options:

  1. Radical surgical resection alone.
  2. Radiation therapy alone.
  3. Surgical resection plus radiation therapy, which is generally administered postoperatively.

Advanced Lesions of the Floor of the Mouth

Standard treatment options:

  1. A combination of surgery and radiation therapy, which is generally administered postoperatively, is often used.
  2. Preoperative radiation therapy is often used for fixed nodes (=5 cm).

Advanced Lesions of the Lower Gingiva

Standard treatment options:

  • Surgery, radiation therapy, or a combination of both are poor controls for far advanced tumors with extensive destruction of the mandible and with nodal metastases.

Advanced Lesions of the Retromolar Trigone

Standard treatment options:

  • Surgical composite resection followed by postoperative radiation therapy.

Advanced Lesions of the Upper Gingiva

Standard treatment options:

  • Surgery in combination with radiation therapy is generally used to treat lesions that are extensive and infiltrating.

Advanced Lesions of the Hard Palate

Standard treatment options:

  • Surgery in combination with radiation therapy is generally used to treat lesions that are extensive and infiltrating.

Treatment options for management of lymph nodes:[5]

Patients with advanced lesions should have elective lymph node radiation therapy or node dissection. The risk of metastases to lymph nodes is increased by high-grade histology, large lesions, spread involving the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle (orbicularis oris).

Standard treatment options:

  1. Radiation therapy alone or neck dissection:
    • N1 (0–2 cm).
    • N2b or N3; all nodes smaller than 2 cm. (A combined surgical and radiation therapy approach should also be considered.)
  2. Radiation therapy and neck dissection:
    • N1 (2–3 cm), N2a, N3.
  3. Surgery followed by radiation therapy is indicated for the following:
    • Multiple positive nodes.
    • Contralateral subclinical metastases.
    • Invasion of tumor through the capsule of the lymph node.
    • N2b or N3 (one or more nodes in each side of the neck, as appropriate, >2 cm).
  4. Radiation therapy prior to surgery:
    • Large fixed nodes.

Treatment options under clinical evaluation (all stage IV lesions):

  1. Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.[6,7,8,9]

    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.[10][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data 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 oral cavity cancer.

    The best chemotherapy to use and the appropriate way to integrate the two modalities is still unresolved.[11]

    Similar approaches in the patient with resectable disease, in whom resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

  2. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, or as adjuvant therapy after surgery are appropriate.[6,12,13,14,15,16,17,18,19]
  3. Novel fractionation radiation therapy clinical trials are under clinical evaluation.[20]

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 lip and oral cavity 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.


  1. Mazeron JJ, Martin M, Brun B, et al.: Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck 14 (2): 85-91, 1992 Mar-Apr.
  2. 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.
  3. Johnson CR, Khandelwal SR, Schmidt-Ullrich RK, et al.: The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. Int J Radiat Oncol Biol Phys 32 (3): 635-41, 1995.
  4. Franceschi D, Gupta R, Spiro RH, et al.: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg 166 (4): 360-5, 1993.
  5. Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA: Lippincott, William & Wilkins, 2009.
  6. 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.
  7. 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.
  8. 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.
  9. Merlano M, Benasso M, Corv˛ 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.
  10. 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.
  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.
  12. 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.
  13. Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer 60 (3): 301-11, 1987.
  14. Toohill RJ, Duncavage JA, Grossmam TW, et al.: The effects of delay in standard treatment due to induction chemotherapy in two randomized prospective studies. Laryngoscope 97 (4): 407-12, 1987.
  15. 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.
  16. Fu KK, Phillips TL, Silverberg IJ, et al.: Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial. J Clin Oncol 5 (9): 1410-8, 1987.
  17. Ryan RF, Krementz ET, Truesdale GL: Salvage of stage IV intraoral squamous cell carcinomas with preoperative 5-fluorouracil. Cancer 57 (4): 699-705, 1986.
  18. Ervin TJ, Clark JR, Weichselbaum RR, et al.: An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol 5 (1): 10-20, 1987.
  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.
  20. Stuschke M, Thames HD: Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. Int J Radiat Oncol Biol Phys 37 (2): 259-67, 1997.
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