Effect of Amifostine on Patients with Lung Cancer Treated with Radiotherapy or Concomitant Chemoradiotherapy:A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective Amifostine is clinically used as a chemical radioprotector. Nevertheless, its efficacy as a radioprotector remains controversial. Methods PubMed, Cochrane Central Register of Controlled Trials, EMBASE, China National Knowledge Infrastructure, and the references of the published results of trials on the efficacy of amifostine in patients with lung cancer and who received radiotherapy or concomitant chemoradiotherapy were searched. The pooled radiation protection efficacy, treatment response, and side effects of amifostine were calculated using RevMan software. Results Twelve randomized controlled trials involving 1000 patients with lung cancer were ultimately analyzed. Results of meta-analysis revealed that the use of amifostine reduced the risk of acute esophageal toxicity(RR, 0.56; 95% CI , 0.39-0.81; P =0.002) and pulmonary toxicity(RR, 0.42; 95% CI , 0.25-0.70; P =0.001). Subgroup analysis also demonstrated that the risk of acute esophageal toxicity and pulmonary toxicity significantly reduced in patients who received chemoradiation concurrent with amifostine or radiation only. Pooled data showed that the use of amifostine did not significantly decrease the risk of late pulmonary toxicity(RR, 0.74; 95% CI , 0.45-1.19; P =0.210). Moreover, subgroup analysis demonstrated that the risk oflate pulmonary toxicity did not significantly decrease in patients who received chemoradiotherapy concomitant with amifostine(RR, 0.84; 95% CI , 0.48-1.46; P =0.540). Amifostine did not exert tumor-protective effects in partial response(RR, 0.98; 95% CI , 0.83-1.15; P =0.800) but improved complete response(RR, 1.50; 95% CI , 1.03-2.18; P =0.030), although publication bias was observed through Egger's test( P =0.000). Moreover, amifostine had no effect on one-year overall survival (RR, 0.94; 95% CI , 0.81-1.09; P =0.400) and two-year overall survival(RR, 1.06; 95% CI , 0.81-1.39; P =0.680) rates. The incidence of neutropenia, a hematologic side effect of amifostine, was not significantly different(RR, 1.02; 95% CI , 0.61-1.71; P =0.940) between the amifostine and control group. The use of amifostine, however, significantly decreased the incidence of thrombocytopenia(RR, 0.45; 95% CI , 0.21-0.94; P =0.030). The most common amifostine-related side effects were nausea, vomiting, and hypotension with average incidence rates of 11%, 14%, and 24%, respectively. Conclusions This systematic review showed that the concurrent administration of amifostine with radiotherapy to patients with lung cancer significantly reduced the risks of acute esophageal toxicity and acute pulmonary toxicity and decreased the incidence of thrombocytopenia without tumor-protecting effects. In addition, the toxicities of amifostine were generally controllable through clinical treatment or resting.