BACKGROUND. For patients with advanced, unresectable squamous-cell carcinoma of the head and neck, radiotherapy is the standard treatment but has poor results. We therefore designed a randomized trial to determine whether alternating chemotherapy with radiotherapy would improve the survival of such patients. METHODS. Patients in the trial had biopsy-confirmed unresectable, previously untreated Stage III or IV, squamous-cell carcinoma of the oral cavity, pharynx, or larynx. They were randomly assigned to chemotherapy consisting of four cycles of intravenous cisplatin (20 mg per square meter of body-surface area per day for five consecutive days) and fluorouracil (200 mg per square meter per day for five consecutive days) alternating with radiotherapy in three two-week courses (20 Gy per course; 2 Gy per day, five days per week), or to radiotherapy alone (up to 70 Gy; 2 Gy per day, five days per week). RESULTS. The 80 patients given chemotherapy alternating with radiotherapy and the 77 given radiotherapy alone were comparable in terms of age, sex, performance status, disease stage, and site of the primary tumor. Complete responses were obtained in 42 percent of the patients in the combined-therapy group and 22 percent of those in the radiotherapy group (P = 0.037). The median survival was 16.5 months in the combined-therapy group and 11.7 months in the radiotherapy group (P less than 0.05); the 3-year survival was 41 percent and 23 percent, respectively. Severe mucositis occurred in 19 percent of the patients in the combined-therapy group and 18 percent of those in the radiotherapy group. CONCLUSIONS. In patients with advanced unresectable squamous-cell carcinoma of the head and neck, chemotherapy alternating with radiotherapy increases the median survival and doubles the probability of survival for three years as compared with radiotherapy alone. However, since local disease cannot be controlled in over half the patients who receive the combined treatment and since almost two thirds die within three years, further improvements in management are necessary.
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Department of Medical Oncology, National Institute for Cancer Research, Genoa, Italy.
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