Two mechanisms of
radiotherapy resistance which are of major importance in various tumour types are tumour-cell repopulation and
hypoxia. ARCON (accelerated
radiotherapy with
carbogen and
nicotinamide) is a new therapeutic strategy that combines
radiation treatment modifications, with the aim of counteracting these resistance mechanisms. To limit clonogenic repopulation during
therapy, the overall duration of the
radiotherapy is reduced, generally by delivering several fractions per day. This accelerated
radiotherapy is combined with inhalation of hyperoxic gas to decrease diffusion-limited
hypoxia, and
nicotinamide, a vasoactive agent, to decrease perfusion-limited
hypoxia. Preclinical studies have been done to test the enhancing effects of these three components of ARCON, individually and in combination, in several experimentally induced tumours and normal tissues. In a mouse mammary
carcinoma, the tumour-control rate obtained with ARCON was the same as that with conventional treatment, but with a radiation dose almost 50% lower. Phase 1 and 2 clinical trials have shown the feasibility and tolerability of ARCON, and have produced promising results in terms of tumour control. In particular in
cancers of the head and neck and bladder, the local tumour-control rates are higher than in other studies, and phase 3 trials for these tumour types are underway. In conjunction with these trials,
hypoxia markers detectable by immunohistochemistry are being tested for their potential use in predictive assays to select patients for ARCON and other
hypoxia-modifying
therapies.