title: Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial.
abstract: OBJECTIVE
  Phase II studies in laryngeal and bladder carcinoma of accelerated radiotherapy with carbogen and nicotinamide (RT+CON) suggested a therapeutic advantage. Therefore, a randomized phase-III trial of RT+CON in locally advanced bladder carcinoma compared to radiotherapy (RT) alone was undertaken.
  
  
  METHODS
  One hundred and sixty-five patients with muscle-invasive transitional cell bladder carcinoma were randomized to RT alone and 168 to RT+CON. This paper reports on compliance and toxicity to nicotinamide (NAM) and carbogen and on early radiation-induced adverse bowel and urinary events.
  
  
  RESULTS
  Of those receiving RT+CON, 65-69% accepted all doses of NAM. Sixty-four percent of patients presented Grade 1 NAM toxicity (nausea or vomiting), which was severe in 13%. Compliance to carbogen was 85% and none (32 fractions) and 2% (20 fractions) of patients presented severe toxicity. The highest prevalence of severe radiation acute morbidity was seen for urinary frequency (RT: 18% and RT+CON: 15%) and for diarrhea (RT: 3% and RT+CON: 5%).
  
  
  CONCLUSIONS
  There is no indication of an increase in radiation-induced morbidity by combining the tumour radiosensitizers carbogen and nicotinamide with radiotherapy. Late morbidity and treatment outcome will ultimately determine if there is a therapeutic benefit.
authors.affiliation: CR-UK Tumour Biology and Radiation Research Group, Northwood, Middlesex, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hoskin
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rojas
authors.forename: Michele I
authors.initials: MI
authors.lastname: Saunders
authors.forename: S M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: K J
authors.initials: KJ
authors.lastname: Motohashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002245:Carbon Dioxide / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009536:Niacinamide / Q000009:adverse effects / Q000627:therapeutic use*; D010100:Oxygen / Q000009:adverse effects / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen