title: International randomized phase 2 study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents.
abstract: OBJECTIVE
  Nasopharyngeal carcinoma (NPC) is a rare but aggressive malignancy in children and adolescents. An international, randomized phase 2 trial was conducted to compare induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (TPF) with cisplatin and 5-fluorouracil (PF) in NPC patients under the age of 21.
  
  
  METHODS
  Patients with stage IIB-IV NPC were randomly assigned, in a 2:1 ratio, to receive TPF or PF 3-weekly for three cycles, followed by chemoradiotherapy. The primary endpoint was the complete response rate achieved with TPF or PF. Docetaxel pharmacokinetics was also evaluated.
  
  
  RESULTS
  Seventy-five patients (median 16 years old) were randomized, with 50 assigned to the TPF group and 25 to the PF group. Overall response was assessed after induction treatment: one patient in the TPF group and none in the PF group had a complete response. Partial response was achieved in 76.0 and 80.0 % in the TPF and PF groups, respectively. The overall safety profile was consistent with findings in adults. The estimated 3-year overall survival rate was 78.0 % for the PF group and 85.7 % for the TPF group (median follow-up 3.3 years). Mean docetaxel area under the curve was 3.41 µg h/mL, compared with 3.51 µg h/mL seen in adult patients.
  
  
  CONCLUSIONS
  This study demonstrated the feasibility of prospective randomized protocols, even for such rare tumors as pediatric NPC. Overall, there were no differences between the two treatment arms in terms of efficacy and toxicity. The pharmacokinetics of docetaxel in pediatric patients at 75 mg/m(2) was similar to those observed in adults.
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian, 1, 20133, Milan, Italy. michela.casanova@istitutotumori.mi.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Casanova
authors.affiliation: School of Medicine, Acibadem University, Istanbul, Turkey.
authors.forename: Enis
authors.initials: E
authors.lastname: Özyar
authors.affiliation: Institut Gustave Roussy, Villejuif Cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Patte
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian, 1, 20133, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Sanofi, Chilly-Mazarin, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Veyrat-Follet
authors.affiliation: National Institute of Oncology, University Mohammed V Souissi, Rabat, Morocco.
authors.forename: Hassan
authors.initials: H
authors.lastname: Errihani
authors.affiliation: Fujian Cancer Hospital, Fujian, China.
authors.forename: Jianji
authors.initials: J
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sun University Cancer Center, East Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Sanofi, Bridgewater, NJ, USA.
authors.forename: Liji
authors.initials: L
authors.lastname: Shen
authors.affiliation: Novartis, East Hanover, NJ, USA.
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Grzegorzewski
authors.affiliation: Institute of Oncology, Hacettepe University, Ankara, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Varan
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols; D002277:Carcinoma; D059248:Chemoradiotherapy / Q000379:methods; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-Fluorouracil; Cisplatin; Docetaxel; Pediatric nasopharyngeal carcinoma; Pharmacokinetics