title: Accelerated radiotherapy with carbogen and nicotinamide for laryngeal cancer: results of a phase III randomized trial.
abstract: OBJECTIVE
  To report the results from a randomized trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen inhalation and nicotinamide (ARCON) in laryngeal cancer.
  
  
  METHODS
  Patients with cT2-4 squamous cell laryngeal cancer were randomly assigned to AR (68 Gy within 36 to 38 days) or ARCON. To limit the risk of laryngeal necrosis, ARCON patients received 64 Gy on the laryngeal cartilage. The primary end point was local control. Secondary end points were regional control, larynx preservation, toxicity, disease-free survival, and overall survival. In a translational side study, the hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies.
  
  
  RESULTS
  From April 2001 to February 2008, 345 patients were accrued. After a median follow-up of 44 months, local tumor control rate at 5 years was 78% for AR versus 79% for ARCON (P = .80), with larynx preservation rates of 84% and 87%, respectively (P = .48). The 5-year regional control was significantly better with ARCON (93%) compared with AR (86%, P = .04). The improvement in regional control was specifically observed in patients with hypoxic tumors and not in patients with well-oxygenated tumors (100% v 55%, respectively; P = .01). AR and ARCON produced equal levels of toxicity.
  
  
  CONCLUSIONS
  Despite lack of benefit in local tumor control for advanced laryngeal cancers, a significant gain in regional control rate, with equal levels of toxicity, was observed in favor of ARCON. The poor regional control of patients with hypoxic tumors is specifically countered by ARCON treatment.
authors.affiliation: Radboud University Nijmegen Medical Centre, the Netherlands.
authors.forename: Geert O
authors.initials: GO
authors.lastname: Janssens
authors.forename: Saskia E
authors.initials: SE
authors.lastname: Rademakers
authors.forename: Chris H
authors.initials: CH
authors.lastname: Terhaard
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Doornaert
authors.forename: Hendrik P
authors.initials: HP
authors.lastname: Bijl
authors.forename: Piet
authors.initials: P
authors.lastname: van den Ende
authors.forename: Alim
authors.initials: A
authors.lastname: Chin
authors.forename: Henri A
authors.initials: HA
authors.lastname: Marres
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: Hoogsteen
authors.forename: Johannes
authors.initials: J
authors.lastname: Bussink
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009536:Niacinamide / Q000009:adverse effects / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage* / Q000009:adverse effects; D018579:Patient Selection; D016016:Proportional Hazards Models; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D014803:Vitamin B Complex / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; D011838:Radiation-Sensitizing Agents; D014803:Vitamin B Complex; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen