Intrinsic radioresistance, tumor hypoxia and ability of cancer cells to undergo 
rapid repopulation during radiotherapy are associated with failure of 
radiotherapy. Tumors with low alpha/beta-ratio values or hypoxic tumors unable 
to undergo re-oxygenation, are unlikely to be eradicated with standard 
radiotherapy. Although the therapeutic efficacy of accelerated regimens based on 
low-dose per fraction may be high since they minimize the adverse role of rapid 
tumor repopulation, the cellular compartment with low alpha/beta-ratio values 
(i.e. hypoxic cells) remains a limiting factor. Accelerated hypofractionation, 
which may be more effective in such tumors, cannot be safely applied unless 
normal tissues are protected. In the present study we assessed the feasibility 
of hypofractionated and accelerated radiotherapy supported by cytoprotection 
(HypoARC) with high dose daily amifostine. Fifteen breast cancer patients with 
locally advanced disease entered radiation-dose escalation protocoL Twelve 
consecutive fractions of 3.5-4Gy (5 fractions/week) were given to the 
breast/chest wall, supraclavicular and axillary area, within 17 days. A high 
dose of amifostine, at 1,000 mg flat dose, was given 20 minutes before each 
radiotherapy fraction. Amifostine administration was well- tolerated with minor 
side-effects (vomiting in 6 out of 15 and hypotention in 2 out of 15 patients). 
Radiation induced acute skin toxicity was negligible (grade 3 in 1 out of 15 
patients). Ten out of 15 patients survived more than 12 months and 7 out of 15 
more than 18 months following HypoARC. None of these patients showed any signs 
of late sequellae, such as lung and myoskeletal fibrosis, or brachial 
plexopathy. Complete and partial responses were obtained in 11 out of 15 (73%) 
and in 4 out of 15 (27%) patients, respectively. High dose daily amifostine 
during hypofractionated radiotherapy is feasible. HypoARC regimen is 
well-tolerated, effective and has minimal acute and late toxicity to normal 
breast, chest and axillary tissues.