title: Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial.
abstract: BACKGROUND
  Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies.
  
  
  METHODS
  Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation. Intravenous chemoradiation comprised 3x100 mg/m(2) cisplatin infusion on Days 1, 22, 43 combined with 70 Gy in 35 daily fractions. The IA chemoradiation treatment arm comprised 4x150 mg/m(2) cisplatin administered in the tumor-feeding artery on Days 1, 8, 15, 22, immediately followed by systemic rescue with sodium thiosulfate with the same radiotherapeutic regimen.
  
  
  RESULTS
  Two patients were excluded from analysis because of nontreatment-related death immediately after randomization (n = 1) and esophageal carcinoma (n = 1). The median follow-up was 33 months 1-104 months. Ninety percent of the patients required tube feeding during treatment. Renal toxicity >grade 2 was 9% in the intravenous compared with 1% in the IA treatment arm (P <or= .0001). There was no difference in locoregional control, disease-free survival (DFS) or overall survival (OS), between the treatment arms. At 3 years, local control, locoregional control, DFS, and OS was .76, .63, .44, .51 in the IA versus .70, .65, .47, .47 in the intravenous treatment arm, respectively.
  
  
  CONCLUSIONS
  Cisplatin-based IA chemoradiation was not superior to intravenous chemoradiation for advanced stage IV head and neck cancer regarding locoregional control and survival.
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam, Netherlands. c.rasch@nki.nl
authors.forename: Coen R N
authors.initials: CR
authors.lastname: Rasch
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.forename: Jan
authors.initials: J
authors.lastname: Schornagel
authors.forename: Oda
authors.initials: O
authors.lastname: Wijers
authors.forename: Jan
authors.initials: J
authors.lastname: Buter
authors.forename: Theo
authors.initials: T
authors.lastname: Gregor
authors.forename: Ruud
authors.initials: R
authors.lastname: Wiggenraad
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: de Boer
authors.forename: Annemiek H
authors.initials: AH
authors.lastname: Ackerstaff
authors.forename: Robert
authors.initials: R
authors.lastname: Kroger
authors.forename: Frank J P
authors.initials: FJ
authors.lastname: Hoebers
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: Balm
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Hilgers
mesh_terms: D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D010349:Patient Compliance