title: Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN.
  
  
  METHODS
  In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250mg/day, 500mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2years; secondary endpoints were LDCR at 1year, objective response rate, progression-free survival, overall survival, and safety and tolerability.
  
  
  RESULTS
  Gefitinib (250 and 500mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p=0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p=0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy.
  
  
  CONCLUSIONS
  Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.
authors.affiliation: St. Luc University Hospital, Brussels, Belgium. vincent.gregoire@uclouvain.be
authors.forename: Vincent
authors.initials: V
authors.lastname: Gregoire
authors.forename: Marc
authors.initials: M
authors.lastname: Hamoir
authors.forename: Changhu
authors.initials: C
authors.lastname: Chen
authors.forename: Madeleine
authors.initials: M
authors.lastname: Kane
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kawecki
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Julka
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Srihari
authors.initials: S
authors.lastname: Prasad
authors.forename: Anil K
authors.initials: AK
authors.lastname: D'Cruz
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Radosevic-Jelic
authors.forename: Rejnish R
authors.initials: RR
authors.lastname: Kumar
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Korzeniowski
authors.forename: Jacek
authors.initials: J
authors.lastname: Fijuth
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
authors.forename: Mark V
authors.initials: MV
authors.lastname: Sellers
authors.forename: Ilian
authors.initials: I
authors.lastname: Tchakov
authors.forename: David
authors.initials: D
authors.lastname: Raben
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D011799:Quinazolines; D002945:Cisplatin; D000077156:Gefitinib