Amifostine (AMF) has been shown to protect some normal tissues from acute 
effects of radiation therapy +/- chemotherapy. We enrolled 62 patients in a 
randomized study investigating the efficacy of AMF: 31 had concurrent 
chemoradiation for non-small cell lung cancer and 31 had the same treatment + 
AMF. AMF reduced the frequency and severity of esophagitis, pneumonitis, and 
neutropenic fever. We have tried to identify patients who get more benefit from 
AMF by checking their DNA repair capability of normal cells. It was hypothesized 
that DNA repair capacity from patients' lymphocytes damaged by bleomycin could 
predict their normal tissue sensitivity to chemoradiation and could be protected 
by AMF. Forty-six of the 62 patients provided pretreatment blood for assessment 
of mutagen sensitivity (MS) using a peripheral lymphocyte assay that infers DNA 
repair capacity from cellular damage remaining after in vitro mutagenic exposure 
and recovery. Bleomycin-induced chromosome breaks in 50 metaphases were counted 
and expressed as the mean number of breaks per cell. Patients with an average of 
more than one break/cell were deemed to exhibit the MS phenotype. Data analysis 
used Pearson's chi-square and Kaplan-Meier survival function estimates with 
Strata 8.2 statistical software. The Log-rank test was used to assess the 
equality of survival function using a P value of .05. Twelve patients (10 AMF, 2 
control) exhibited the MS phenotype. The remaining 34 patients (13 AMF, 21 
control) were considered to have normal DNA repair. There were no significant 
differences in overall survival, disease specific survival, or local control by 
MS. Those with high MS had shorter distant metastasis-free survival compared 
with low MS patients ( P = .029). There were no differences in severe 
esophagitis or neutropenic fever by MS. Both high and low MS patients from the 
control group developed severe lung fibrosis compared with five of 21 who had 
AMF ( P = .025). The incidence of grade 3/4 lung fibrosis was two of 10 with AMF 
compared with two of two in the control group ( P = .025) with higher MS. Higher 
MS was associated with shorter distant metastasis-free survival and more 
frequent grade 3/4 lung fibrosis. AMF reduced the incidence of grade 3/4 lung 
fibrosis among higher MS. These data suggest that MS might help identify 
subgroups of patients who could receive more benefit from AMF with respect to 
lung damage.