ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC

Background: Non small cell lung cancers (NSCLC) are rapidly proliferating t umours, which are characterized by the presence of extensive hypoxic compon ents, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia o n the outcome of radiotherapy for these tumours. Aim: This pilot study was aimed at determining the feasibility and tumour r esponse rates that can be achieved with an ARCON regime in patients with lo cally advanced, staged IIIA or B, NSCLC tumours. Methods, The phase I/II study included three steps: accelerated fractionati on (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11) and AF with both carbon a nd nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. Results: The incidence of grade 3 + acute toxicity during the irradiation d id not exceed 10%, neither in the lung parenchyma nor in the mediastinum. N o significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showe d grade 2 or 3 emesis in all the steps, of the 25 patients entered in the t wo Nicotinamide containing steps 10 (40%) developed grade 2 or greater reac tions which significantly detracted from their quality of life. There was n o significant difference in tumour clearance rate among the three steps. Th e percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. Conclusion: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effect s but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant diffe rence in time to progression among the three study steps. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.