Overview of combined modality therapies for head and neck cancer

The survival rate is 40% for patients with advanced squamous cell carcinoma of the head and neck whose tumors are completely resected and 20% for those with unresectable tumors treated with radiotherapy alone. During the past 10 years, combined modality approaches have been developed in an effort to enhance locoregional disease control, reduce distant metastases, and preserve anatomic function. They include the following: (a) neoadjuvant chemotherapy followed by standard therapy with surgery and/or radiation, (b) adjuvant chemotherapy after surgery or radiotherapy with or without neoadjuvant chemotherapy, and (c) neoadjuvant chemotherapy concurrent with radiotherapy. Even early studies of cisplatin plus fluorouracil (5-FU) reported 50%-90% overall response rates, and this is the main drug combination used in clinical trials. In the Veterans Affairs Cooperative Study Program, 5-FU and cisplatin followed by radiotherapy achieved a 49% complete response rate and preservation of the larynx in 64% of the patients. These results supported the findings of other nonrandomized trials that sequential induction chemotherapy and radiotherapy results in laryngeal preservation without compromising overall survival. The Head and Neck Cancer Intergroup Trial compared adjuvant postoperative cisplatin plus 5-FU prior to radiotherapy with postoperative radiotherapy. Survival at 4 years was 44% with radiotherapy alone and 48% with chemotherapy and radiotherapy. Biochemical modulation of 5-FU with leucovorin and biologic response modifiers such as interferon has achieved complete response rates as high as 66%, but severe mucositis continues to be the dose-limiting toxic effect. Standard radiotherapy for advanced nasopharyngeal carcinoma--a unique type of head and neck cancer--resulted in 5-year survival of 10%-40%, but neoadjuvant chemotherapy plus radiotherapy has achieved overall complete response rates greater than 80% with median survival of 5 or more years. We conclude that curability of nasopharyngeal carcinoma with a combined modality approach appears to be an achievable goal, but adequate evaluation in large-scale randomized trials is hampered by low accrual to clinical trials. In summary, neoadjuvant therapy for squamous cell head and neck carcinoma results in complete response rates of 22%-66%, but addition of adjuvant therapy may be necessary for a survival advantage over standard therapy. Although concurrent chemoradiotherapy has produced increased survival, additional trials are needed to determine optimal dosages.