ARCON: accelerated radiotherapy with carbogen and nicotinamide in head andneck squamous cell carcinomas. The experience of the Cooperative Group of Radiotherapy of the European Organization for Research and Treatment of Cancer (EORTC)

Background: Since there is increasing evidence that both acute (perfusion-l imited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% ox ygen-5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARC ON) should reduce the impact of these factors of radioresistance. Aim: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieve d with this regime in patients with locally advanced tumors of the head and neck. Methods: A phase I/II study conducted between 1993 and 1996 by the Co-opera tive Group of Radiotherapy of the EORTC included three consecutive steps: a ccelerated fractionation (AF) combined with carbogen (11 analyzable patient s), AF combined with the daily administration of nicotinamide (n = 10), and AF with both carbogen and nicotinamide (n = 17). Radiotherapy was based on an accelerated regime (72 Gy in 5.5 weeks). Nicotinamide was delivered 90 min before the first irradiation session, at a daily dose of 6 g. Carbogen breathing started 5 min before irradiation and lasted throughout the entire radiotherapy sessions. Results: No significant different in loco-regional toxicity was found among the three study steps, when carbogen and nicotinamide, either alone or in combination, were combined with AF. The feasibility of the ARCON protocol, as proposed in the present EORTC study, appears to be significantly impaire d when nicotinamide is added, at a daily dose of 6 g, to AF and carbogen, i n an unselected group of patients. More than 20% of patients experienced gr ade 2 or 3 emesis. It also demonstrates, in unselected groups of patients, no significant difference in tumor response and local control when carbogen and nicotinamide, either alone or in combination, are added to accelerated radiotherapy. The percentages of objective response at 2 months were 81, 7 0 and 87%, respectively. Conclusion: Future ARCON trials should target selected head and neck tumor localizations and stages, and a lower nicotinamide dose is needed to reduce severe upper gastro-intestinal toxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.