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

BACKGROUND The current study presents mature results from a Phase III randomized trial comparing radiation therapy and concurrent chemoradiotherapy in patients with resectable American Joint Committee on Cancer Stage III and IV disease. METHODS One hundred patients were randomized to receive either radiation therapy alone (Arm A) (at a dose of between 66–72 grays [Gy] at 1.8–2 Gy per day) and the identical radiation therapy with concurrent chemotherapy (Arm B) (5‐fluorouracil, 1000 mg/m2/day, and cisplatin, 20 mg/m2/day, both given as continuous intravenous infusions over 4 days beginning on Days 1 and 22 of the radiation therapy). Primary site resection was planned for patients with residual or recurrent local disease. Cervical lymph node dissection was performed for regional persistent disease or recurrence, or if N2‐3 disease was present at the time of presentation. RESULTS After completing all therapy including surgery, 82% of the patients in Arm A and 98% of the patients in Arm B had been rendered disease free (P = 0.02). At a median follow‐up of 5 years (range, 3–8 years), the 5‐year Kaplan–Meier projections for overall survival for Arm A versus Arm B were 48% versus 50% (P = 0.55). Kaplan–Meier projections for the recurrence free interval were 51% versus 62% (P = 0.04), projections for a distant metastasis free interval were 75% versus 84% (P = 0.09), projections for overall survival with primary site preservation were 34% versus 42% (P = 0.004), and projections for local control without surgical resection were 45% versus 77% (P < 0.001). Salvage surgery proved to be successful in 63% and 73%, respectively, of the Arm A and Arm B patients with primary site failure. Unrelated death while free of disease occurred in 22% and 32%, respectively, of Arm A and Arm B patients (P = 0.26). CONCLUSIONS The addition of concurrent chemotherapy to definitive radiation in patients with resectable Stage III and IV squamous cell carcinoma of the head and neck improves the likelihood of disease clearance, a recurrence free interval, and primary site preservation. However, overall survival does not appear to be improved, reflecting both effective surgical salvage after local recurrence and competing causes of death. Cancer 2000;88:876–83. © 2000 American Cancer Society. This Phase III randomized trial compared radiation therapy with radiation and concurrent chemotherapy with cisplatin and 5‐fluorouracil in 100 patients with American Joint Committee on Cancer Stage III