Patients with head and neck cancer can be categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease. Comorbidities associated with tobacco and alcohol abuse can affect treatment outcome.

Localized Disease -  Nearly one-third of patients have localized disease; that is, T1 or T2 (stage I or stage II) lesions without detectable lymph node involvement or distant metastases. These lesions are treated with curative intent by surgery or radiation therapy. The choice of modality differs according to institutional expertise. Radiation therapy is often preferred for laryngeal cancer to preserve voice function, and surgery is preferred for small lesions in the oral cavity to avoid the long-term complications of radiation, such as xerostomia and dental decay. Overall 5-year survival is 60 to 90%.

Locally or Regionally Advanced Disease -  Locally or regionally advanced disease -  disease with a large primary tumor and/or lymph node metastases -  can also be treated with curative intent, but not with surgery or radiation therapy alone. Combined modality therapy including surgery, radiation therapy, and chemotherapy is most successful. Concomitant chemotherapy and radiation therapy appears to be most effective.

INDUCTION CHEMOTHERAPY
In this strategy, patients receive chemotherapy [usually cisplatin and fluorouracil (5FU)] before surgery and radiation therapy. Most patients who receive three cycles show tumor reduction, and the response is clinically “complete” in up to half. This “sequential” multimodality therapy does not cure more patients than surgery plus radiation therapy alone. However, induction chemotherapy allows for organ preservation in patients with laryngeal and hypopharyngeal cancer.

CONCOMITANT CHEMORADIOTHERAPY
With the concomitant strategy, chemotherapy and radiation therapy are given simultaneously rather than sequentially. Because most patients with head and neck cancer develop recurrent disease in the head and neck area, this approach is aimed at killing radiation-resistant cancer cells with chemotherapy. In addition, chemotherapy can enhance cell killing by radiation therapy. Toxicity (mucositis) is increased with concomitant chemoradiotherapy; however, meta-analysis of randomized trials documents an improvement in 5-year survival of 8% with concomitant 5FU and radiation therapy. Results seem even better with 5FU and cisplatin plus radiation therapy. Five-year survival is 34 to 50%. In addition, concomitant chemoradiotherapy produces better laryngectomy-free survival (organ preservation) than induction chemotherapy in patients with advanced larynx cancer. The use of radiation therapy together with cisplatin has produced markedly improved survival in patients with advanced nasopharyngeal cancer. The success of concomitant chemoradiotherapy in patients with unresectable disease has led to the testing of a similar approach in patients with resected disease as a postoperative therapy, but results to date have not convincingly shown improvement over postoperative radiation therapy alone.

Recurrent and/or Metastatic Disease-  Patients with recurrent and/or metastatic disease are, with few exceptions, treated with palliative intent. Some patients may require local or regional radiation therapy for pain control, but most are given chemotherapy. Response rates to chemotherapy average only 30 to 50%; the duration of response averages only 3 months, and the median survival time is 6 to 8 months. Therefore, chemotherapy provides transient symptomatic benefit. Drugs with single-agent activity in this setting include methotrexate, 5FU, cisplatin, paclitaxel, and docetaxel. Combinations of cisplatin and 5FU, carboplatin and 5FU, and cisplatin or carboplatin and paclitaxel or docetaxel are frequently used.

Chemoprevention

β-Carotene and cis-retinoic acid can lead to the regression of leukoplakia. However, cis-retinoic acid does not reduce the incidence of second primaries.

Treatment Complications

Complications from treatment of head and neck cancer are usually related to the extent of surgery. Several attempts have been made to limit the extent of surgery or to replace it with chemotherapy and radiation therapy. Acute complications of radiation include mucositis and dysphagia. Long-term complications include xerostomia, loss of taste, decreased tongue mobility, second malignancies, dysphagia, and neck fibrosis. The complications of chemotherapy vary with the regimen used but usually include myelosuppression, mucositis, nausea and vomiting, and nephrotoxicity (with cisplatin).

Salivary Gland Tumors

Most benign salivary gland tumors are treated with surgical excision, and patients with invasive salivary gland tumors are treated with surgery and radiation therapy. Neutron radiation may be particularly effective. These tumors may recur regionally; adenoidcystic carcinoma has a tendency to recur along the nerve tracks. Distant metastases may occur as late as 10 to 20 years after the initial diagnosis. For metastatic disease, therapy is given with palliative intent, usually chemotherapy with doxorubicin and/or cisplatin.

Further Reading

_{CALIFANO J et al: Genetic progression model for head and neck cancer: Implications for field cancerization. Cancer Res 56:2488, 1996}

FORASTIERE A et al: Head and neck cancer. N Engl J Med 345:1890, 2001

LAMONT EB, VOKES EE : Chemotherapy in the management of squamous-cell carcinoma of the head and neck. Lancet Oncol 2:261, 2001

LICITRA L, VERMORKEN JB : Is there still a role for neoadjuvant chemotherapy in head and neck cancer? Ann Oncol 15:7, 2004

RICE DH : Salivary gland disorders. Neoplastic and nonneoplastic. Med Clin North Am 83:197, 1999

VOKES E et al: Weekly carboplatin and paclitaxel followed by concomitant TFHX chemoradiotherapy: Curative and organ preserving therapy for advanced head and neck cancer. J Clin Oncol 21:320, 2003

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