title: Five-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.
abstract: BACKGROUND
  In 1992, we reported the first analysis of a randomized trial comparing alternating radiotherapy and chemotherapy with radiotherapy 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.
  
  
  OBJECTIVE
  After an additional 2 years of follow-up, we again compared the efficacy of the two treatment regimens, with attention paid to differences in overall survival, progression-free survival, and locoregional relapse-free survival.
  
  
  METHODS
  One hundred fifty-seven patients with untreated, unresectable squamous cell carcinoma of the head and neck were randomly assigned to receive either chemotherapy (four courses of cisplatin [20 mg/m2] and fluorouracil [200 mg/m2], 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 radiotherapy 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 effects associated with the two treatment regimens were compared. Overall survival, progression-free survival, and locoregional relapse-free survival were calculated according to the Kaplan-Meier method; the logrank test was used to compare survival parameters between the two patient groups. Reported P values are two-sided.
  
  
  RESULTS
  As reported previously, toxic effects associated with the combined therapy included both chemotherapy- and radiotherapy-related effects; however, the incidence and severity of mucositis were nearly identical among patients in the two treatment arms. The combined treatment was associated with a statistically significant increase in the frequency of complete response (i.e., the disappearance of clinically detectable disease for at least 4 weeks) (43% for the combined-treatment group compared with 22% for the radiotherapy-only group; P = .037, chi-squared test). Five-year estimates of overall survival in the combined-treatment group compared with the radiotherapy-only group were 24% (95% confidence interval [CI] = 14%-40%) and 10% (95% CI = 4%-24%), respectively (P = .01, logrank test). The estimates of progression-free survival at 5 years in the combined-treatment group compared with the radiotherapy-only group were 21% (95% CI = 11%-37%) and 9% (95% CI = 3%-22%), respectively (P = .008, logrank test). Finally, the 5-year estimates of locoregional relapse-free survival were 64% (95% CI = 36%-84%) in the combined-treatment group and 32% (95% CI = 10%-65%) in the radiotherapy-only group (P = .038, logrank test).
  
  
  CONCLUSIONS
  The superiority of alternating chemotherapy and radiotherapy over radiotherapy alone in treating unresectable squamous cell carcinoma of the head and neck seen at 3 years was confirmed at 5 years. However, additional trials must be conducted before considering the combined approach as standard therapy.
authors.affiliation: Divisione Oncologia Medica I'Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Merlano
authors.forename: M
authors.initials: M
authors.lastname: Benasso
authors.forename: R
authors.initials: R
authors.lastname: Corvò
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: V
authors.initials: V
authors.lastname: Vitale
authors.forename: F
authors.initials: F
authors.lastname: Blengio
authors.forename: G
authors.initials: G
authors.lastname: Numico
authors.forename: G
authors.initials: G
authors.lastname: Margarino
authors.forename: L
authors.initials: L
authors.lastname: Bonelli
authors.forename: L
authors.initials: L
authors.lastname: Santi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D002945:Cisplatin; D005472:Fluorouracil