title: A randomized phase II study comparing sequential versus simultaneous chemo-radiotherapy in patients with unresectable locally advanced squamous cell cancer of the head and neck.
abstract: BACKGROUND
  Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing.
  
  
  METHODS
  A randomized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment).
  
  
  RESULTS
  At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01).
  
  
  CONCLUSIONS
  In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone.
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pinnarò
authors.forename: M C
authors.initials: MC
authors.lastname: Cercato
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.forename: P
authors.initials: P
authors.lastname: Carlini
authors.forename: M R
authors.initials: MR
authors.lastname: Del Vecchio
authors.forename: F A
authors.initials: FA
authors.lastname: Impiombato
authors.forename: F
authors.initials: F
authors.lastname: Marzetti
authors.forename: M
authors.initials: M
authors.lastname: Milella
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010349:Patient Compliance; D010689:Phlebitis / Q000139:chemically induced; D012074:Remission Induction
chemical_list: D002945:Cisplatin; D005472:Fluorouracil