Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma

J Clin Oncol. 2010 Nov 20;28(33):4912-8. doi: 10.1200/JCO.2010.28.4950. Epub 2010 Oct 18.


Purpose: Phase II clinical studies suggest that hypoxic modification with carbogen and nicotinamide (CON) may increase the efficacy of radiotherapy (RT).

Patients and methods: Three hundred thirty-three patients with locally advanced bladder carcinoma were randomly assigned to RT alone versus RT with CON. A schedule of either 55 Gy in 20 fractions in 4 weeks or 64 Gy in 32 fractions in 6.5 weeks was used. The primary end point was cystoscopic control at 6 months (CC(6m)) and secondary end points were overall survival (OS), local relapse-free survival (RFS), urinary and rectal morbidity.

Results: CC(6m) was 81% for RT + CON and 76% for RT alone (P = .3); however, just more than half of patients underwent cystoscopy at that time. Three-year estimates of OS were 59% and 46% (P = .04) and 3-year estimates of RFS were 54% and 43% (P = .06) for RT + CON versus RT alone. Risk of death was 14% lower with RT + CON (P = .04). In multivariate comparison, RT + CON significantly reduced the risk of relapse (P = .05) and death (P = .03). There was no evidence that differences in late urinary or GI morbidity between treatment groups or between fractionation schedules were significant.

Conclusion: RT + CON produced a small nonsignificant improvement in CC(6m). Differences in OS, risk of death, and local relapse were significantly in favor of RT + CON. Late morbidity was similar in both trial arms. Results indicate a benefit of adding CON to radical RT.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carbon Dioxide / administration & dosage*
  • Cystectomy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Niacinamide / administration & dosage*
  • Oxygen / administration & dosage*
  • Radiation-Sensitizing Agents / administration & dosage*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / radiotherapy*


  • Radiation-Sensitizing Agents
  • Carbon Dioxide
  • Niacinamide
  • carbogen
  • Oxygen