title: Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.
abstract: OBJECTIVE
  To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC).
  
  
  METHODS
  Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy).
  
  
  RESULTS
  A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001).
  
  
  CONCLUSIONS
  Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario 12 de Octubre de Madrid, Carretera de Andalucía, km 5,400, 28041, Madrid, Spain. rhitt@h12o.es
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hitt
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Pousa
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Trufero
authors.forename: Vicente
authors.initials: V
authors.lastname: Escrig
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rizo
authors.forename: Dolores
authors.initials: D
authors.lastname: Isla
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Vega
authors.forename: Juan L
authors.initials: JL
authors.lastname: Martí
authors.forename: Francisco
authors.initials: F
authors.lastname: Lobo
authors.forename: Pedro
authors.initials: P
authors.lastname: Pastor
authors.forename: Vicente
authors.initials: V
authors.lastname: Valentí
authors.forename: Joaquín
authors.initials: J
authors.lastname: Belón
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sánchez
authors.forename: Carlos
authors.initials: C
authors.lastname: Chaib
authors.forename: Cinta
authors.initials: C
authors.lastname: Pallarés
authors.forename: Antonio
authors.initials: A
authors.lastname: Antón
authors.forename: Andrés
authors.initials: A
authors.lastname: Cervantes
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortés-Funes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010349:Patient Compliance; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D013030:Spain; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil