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.

中文翻译：

---

诱变敏感性可以预测氨磷汀对通过放化疗治疗的局部晚期非小细胞肺癌患者的肺保护作用。

氨磷汀（AMF）已被证明可以保护某些正常组织免受放射疗法+/-化疗的急性影响。我们在一项随机研究中招募了62名患者，研究AMF的疗效：31例同时进行了非小细胞肺癌的化学放疗，而31例接受了+ AMF的相同治疗。AMF减少了食道炎，肺炎和中性粒细胞减少的频率和严重程度。我们试图通过检查正常细胞的DNA修复能力来确定从AMF中受益更多的患者。据推测，博来霉素对患者淋巴细胞的DNA修复能力可以预测其正常组织对化学放射的敏感性，并可以被AMF保护。62名患者中的46名患者使用外周淋巴细胞测定法提供了用于评估诱变敏感性（MS）的预处理血液，该方法从体外诱变暴露和恢复后剩余的细胞损伤中推断出DNA修复能力。对博莱霉素诱导的50个中期染色体断裂进行计数，并表示为每个细胞断裂的平均数。平均每个细胞具有一个以上中断的患者被视为表现出MS表型。数据分析使用带Strata 8.2统计软件的Pearson卡方和Kaplan-Meier生存函数估计。对数秩检验用于评估生存功能的相等性，P值为0.05。12位患者（10 AMF，2位对照）表现出MS表型。其余34位患者（13位AMF，21位对照）被认为具有正常的DNA修复。MS的总体生存率，疾病特异性生存率或局部控制率无显着差异。与低MS患者相比，高MS患者的远处无转移生存期短（P = .029）。MS对重度食管炎或中性粒细胞减少没有影响。对照组的高MS患者和低MS患者均出现严重的肺纤维化，而21例中有5例患有AMF（P = .025）。AMF发生的3/4级肺纤维化的发生率为10的2分，而MS较高的对照组为2分之2（P = .025）。较高的MS与较短的无远处转移生存和更频繁的3/4级肺纤维化相关。在较高的MS中，AMF降低了3/4级肺纤维化的发生率。