title: Alternating chemoradiotherapy versus partly accelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck: results from a phase III randomized trial.
abstract: BACKGROUND
  The authors previously have found that in patients with locally advanced squamous cell carcinoma of the head and neck (SCC-HN), alternating chemoradiotherapy (ALT) was superior to low-total-dose conventional radiotherapy alone. The purpose of this randomized trial was to compare the same chemoradiotherapy approach with high-total-dose partly accelerated radiotherapy.
  
  
  METHODS
  During 6 years, 136 consecutive patients with previously untreated unfavorable Stage II or Stage III-IV (International Union Against Cancer) SCC of the oral cavity, pharynx, and larynx were enrolled. They were randomly assigned to chemotherapy consisting of 4 cycles of intravenous cisplatin (20 mg/m(2) of body surface area per day for 5 consecutive days) and 5-fluorouracil (200 mg/m(2) per day for 5 consecutive days; weeks 1, 4, 7, and 10) alternated with three 2-week courses of radiotherapy (20 grays [Gy] per course, 2 Gy per day, 5 days per week; ALT, 70 patients) or to partly accelerated radiotherapy with final concomitant boost technique (75 Gy/40 fractions in 6 weeks; partly accelerated radiotherapy [PA-RT], 66 patients).
  
  
  RESULTS
  At the median follow-up of 60 months (range, 30-102 months), no statistical differences were observed in overall survival, progression free survival, or locoregional control between the 2 treatments. Actuarial 3-year overall survival and progression free survival were 37% and 35%, respectively, in the ALT group and 29% and 27%, respectively, in PA-RT group. The median overall survival and progression free survival were 24 and 15 months, respectively, in the ALT arm and 18 and 11 months, respectively, in PA-RT arm. Actuarial 3-year locoregional control rates were 32% in the ALT group and 27% in the PA-RT group. At multivariate analysis, tumor classification was the only factor that emerged as a significant independent variable affecting overall survival. Patients treated in the PA-RT arm experienced higher Grade 3+ (World Health Organization) acute skin and mucosal reactions than patients in the ALT arm. Moreover, local late mucosal and skin toxicities occurred more often in patients treated with PA-RT.
  
  
  CONCLUSIONS
  This trial failed to disclose statistically significant differences in the outcome of patients treated with either ALT or PA-RT. Therefore, definitive conclusions could not be made. However, acute skin effects and late mucosal and skin toxicities above the clavicles appeared to be significantly lower with chemoradiotherapy.
authors.affiliation: Oncologia Radioterapica, National Cancer Research Institute, Genoa, Italy. corvo@hp380.ist.unige.it
authors.forename: R
authors.initials: R
authors.lastname: Corvò
authors.forename: M
authors.initials: M
authors.lastname: Benasso
authors.forename: G
authors.initials: G
authors.lastname: Sanguineti
authors.forename: R
authors.initials: R
authors.lastname: Lionetto
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: G
authors.initials: G
authors.lastname: Margarino
authors.forename: E
authors.initials: E
authors.lastname: Pallestrini
authors.forename: M
authors.initials: M
authors.lastname: Merlano
authors.forename: V
authors.initials: V
authors.lastname: Vitale
authors.forename: R
authors.initials: R
authors.lastname: Rosso
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology; D010349:Patient Compliance; D012044:Regression Analysis; D016896:Treatment Outcome