Combined With Accelerated Radiation and Carbogen


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Oral nicotinamide has also been evaluated as a radiotherapy enhancer for several different cancer types as part of a combination that includes accelerated radiotherapy, carbogen, and nicotinamide (ACORN).

Previous studies found that ACORN, which included a single oral dose of 85 mg/kg or 6 g per day of nicotinamide, did not improve overall survival (OS) and/or tumor control among patients with glioblastoma, non–small cell lung cancer, or head and neck squamous cell carcinoma.6-9 Tolerability, however, was an issue with these high doses of nicotinamide, which was associated with nausea and vomiting that frequently led to discontinuation.

Several studies, however, demonstrated that ACORN may, at lower doses, improve outcomes among patients with other cancer types. A phase 3 study of 333 patients with locally advanced bladder cancer randomly assigned patients to receive ACORN (60 mg/kg nicotinamide) or radiotherapy alone.10 ACORN resulted in a prolonged OS (59% vs 46%; P = .04) and improved recurrence-free survival (54% vs 43%; P = .06) compared with placebo at 3 years. The rates of gastrointestinal morbidity were similar between groups.

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A phase 3 trial of patients with cT2-4 squamous cell laryngeal cancer demonstrated that ACORN (60 mg/kg nicotinamide) significantly improved 2- and 5-year regional control (95% and 93%, respectively) compared with radiotherapy alone (88% and 86%, respectively; P = .04), particularly among patients with hypoxic tumors.11 Local tumor control, larynx preservation rates, OS, and disease-free survival, however, were similar between the 2 arms.

Conclusions

Results from clinical trials suggest that oral nicotinamide may reduce the number and size of AKs and prevent the development of new non-melanoma skin cancers among patients at high risk. As part of a regimen that also includes accelerated radiotherapy and carbogen, nicotinamide may improve outcomes among patients with locally advanced bladder cancer. Yet while nicotinamide is generally well-tolerated, higher doses can cause treatment-limiting nausea and vomiting.

References

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  8. Bernier J, Denekamp J, Rojas A, et al. ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Cooperative group of radiotherapy of the European Organization for Research and Treatment of Cancer (EORTC). Radiother Oncol. 2000;55:111-9.
  9. Simon JM, Noel G, Chiras J, et al. Radiotherapy and chemotherapy with or without carbogen and nicotinamide in inoperable biopsy-proven glioblastoma multiforme. Radiother Oncol. 2003;67:45-51.
  10. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI. Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol. 2010;28:4912-8. doi: 10.1200/JCO.2010.28.4950
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