A PHASE I II TRIAL OF TWICE-DAILY IRRADIATION AND CONCURRENT CHEMOTHERAPY FOR LOCALLY ADVANCED SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK/

Purpose: This study was designed to test the toxicity and efficacy of a regimen of twice daily irradiation and concurrent multiagent chemoth erapy for patients with locally advanced squamous cell carcinoma of th e head and neck. Methods and Materials: This was a prospective Phase I /II trial. Patients received 125 cGy b.i.d. to 7000 cGy with a 6 hr in terfraction interval. Chemotherapy was given during weeks 1 and 6 of i rradiation and consisted of a 5 day infusion of 5-fluorouracil at 600 mg/M(2)/day and 5 daily injections of cisplatin at 12 mg/M(2)/day. Two additional cycles of chemotherapy were given after the completion of radiotherapy. Results: Forty-six patients were evaluable: 28 had techn ically unresectable disease and 18 had resectable tumors. All had Stag e III or IV disease: 84% had T3 or T4 primaries while 53% had greater than or equal to N2 neck disease. The primary acute toxicity, confluen t mucositis, was seen in 74% of patients. Late side effects occurred i n four patients. Median follow-up is 36 months (range 25-44 months). K aplan-Meier estimates of 2-year disease-free survival and overall surv ival are 65% and 73%, respectively, while 2-year local regional contro l and distant disease-free survival are 72% and 88%, respectively. Mul tivariate analysis revealed that resectability and receiving > 2 cycle s of chemotherapy significantly influenced local regional control whil e age < 60 significantly influenced disease-free survival. Conclusion: This form of treatment can be delivered safely. The encouraging resul ts have led to the initiation of a Phase III trial comparing this regi men with b.i.d. radiation alone.