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The Effect of Carbogen Breathing and Nicotinamide Added to Standard (Chemo)Radiation Treatment of Advanced Cervical Cancer in Indonesia
  1. Willem Jan van Weelden, MD*,
  2. Sri Mutya Sekarutami, MD, PhD,
  3. Ruud L.M. Bekkers, MD, PhD,
  4. Johannes H. Kaanders, MD, PhD*,
  5. Jan Bussink, MD, PhD*,
  6. Soehartati Gondhowiardjo, MD, PhD,
  7. Jan Willem Leer, MD, PhD* and
  8. Paul N. Span, PhD*
  1. *Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands;
  2. Department of Radiotherapy, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; and
  3. Department of Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands.
  1. Address correspondence and reprint requests to Paul N. Span, PhD, Department of Radiation Oncology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail:


Objective Chemoradiation is the standard therapy for advanced stages of cervical cancer. In developing countries, where 80% of cervical cancers occur, this is not always available. Carbogen breathing and oral nicotinamide (CON) therapy, aimed at overcoming tumor hypoxia, has shown to improve treatment efficacy in some epithelial tumors. This study investigates the effect of CON during (chemo)radiation of advanced stages of cervical cancer on overall survival, local and regional control, and toxicity.

Methods From December 2006 to February 2010, 139 patients with stage IB2 to IVA cervical cancer were nonrandomly assigned to receive radiotherapy (RT) or chemoradiation (CRT) with or without CON. Differences in overall survival, local and regional control after 1 year, and toxicity were assessed in 113 evaluable patients. Thirty-two patients received RT, 16 received CRT, 45 received CON-RT, and 20 received CON-CRT.

Results The CON-RT and RT groups contained significantly more patients with a poor performance status and IIIB and IVA tumors. Despite these differences in baseline characteristics, overall survival and local and regional control at 1 year were not significantly different (P = 0.10 and P = 0.19, respectively). Toxicity scores also did not differ (P = 0.60 and P = 0.73 for acute and late toxicity).

Conclusions Addition of CON to standard (chemo)radiation gives comparable survival and control rates. The effect of CON might be underestimated due to differences in baseline characteristics. Because chemotherapy cannot always be (completely) administered in low-resource settings, CON could be a worthy substitute. The CON treatment is feasible and safe.

  • Oxygen modification
  • Radiotherapy
  • Chemotherapy
  • Cervical cancer

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  • This work was funded by a grant supplied by the Dutch Cancer Society.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (

  • The authors declare no conflicts of interest.