5-YEAR UPDATE OF A RANDOMIZED TRIAL OF ALTERNATING RADIOTHERAPY AND CHEMOTHERAPY COMPARED WITH RADIOTHERAPY ALONE IN TREATMENT OF UNRESECTABLE SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Background: In 1992, we reported the first analysis of a randomized tr ial comparing alternating radiotherapy and chemotherapy with radiother apy alone in the treatment of squamous cell carcinoma of the head and neck. The results of that 3-year analysis indicated that the combined treatment had superior efficacy. Purpose: After an additional 2 years of follow-up, we again compared the efficacy of the two treatment regi mens, with attention paid to differences in overall survival, progress ion-free survival, and locoregional relapse-free survival. Methods: On e hundred fifty-seven patients with untreated, unresectable squamous c ell carcinoma of the head and neck were randomly assigned to receive e ither chemotherapy (four courses of cisplatin [20 mg/m(2)] and fluorou racil [200 mg/m(2)], given daily for 5 consecutive days during weeks 1 , 4, 7, and 10) plus radiotherapy (three courses of 20 Gy each, given in fractions of 2 Gy per day during weeks 2-3, 5-6, and 8-9) or radiot herapy alone (70 Gy total dose, given in fractions of 2 Gy per day, 5 days per week). Eighty patients received the combined therapy, and 77 were treated with radiotherapy alone. Responses, failures, and toxic e ffects associated with the two treatment regimens were compared. Overa ll survival, progression-free survival, and locoregional relapse-free survival were calculated according to the Kaplan-Meier method; the log rank test was used to compare survival parameters between the two pati ent groups. Reported P values are two-sided. Results: As reported prev iously, toxic effects associated with the combined therapy included bo th chemotherapy- and radiotherapy-related effects; however, the incide nce and severity of mucositis were nearly identical among patients in the two treatment arms. The combined treatment was associated with a s tatistically significant increase in the frequency of complete respons e (i.e., the disappearance of clinically detectable disease for at lea st 4 weeks) (43% for the combined-treatment group compared with 22% fo r the radiotherapy- only group; P = .037, chi-squared test). Five-year estimates of overall survival in the combined-treatment group compare d with the radiotherapy-only group were 24% (95% confidence interval [ CI] = 14%-40%) and 10% (95% CI = 4%-24%), respectively (P = .01, logra nk test). The estimates of progression-free survival at 5 years in the combined-treatment group compared with the radiotherapy-only group we re 21% (95% CI = 11%-37%) and 9% (95% CI = 3%-22%), respectively (P = .008, logrank test). Finally, the 5-year estimates of locoregional rel apse-free survival were 64% (95% CI = 36%-84%) in the combined-treatme nt group and 32% (95% CI = 10%-65%) in the radiotherapy-only group (P = .038, logrank test). Conclusions and Implications: The superiority o f alternating chemotherapy and radiotherapy over radiotherapy treating unresectable carcinoma of the head and neck seen at 3 years was confi rmed at 5 years. However, additional trials must be conducted before c onsidering the combined approach as standard therapy.