Effect of Amifostine in Head and Neck Cancer Patients Treated with Radiotherapy: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Abstract

BackgroundAmifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent.MethodsBy searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs) about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software.ResultsSeventeen trials including a total of 1167 patients (604 and 563 each arm) were analyzed in the meta-analysis. The pooled data showed that the use of amifostine significantly reduce the risk of developing Grade3–4 mucositis (relative risk [RR],0.72; 95% confidence interval [CI],0.54–0.95; p<0.00001), Grade 2–4 acute xerostomia (RR,0.70; 95%CI,0.52–0.96; p = 0.02), or late xerostomia (RR,0.60; 95%CI,0.49–0.74; p<0.00001) and Grade 3–4 dysphagia (RR,0.39; 95%CI,0.17–0.92; p = 0.03). However, subgroup analysis demonstrated that no statistically significant reduction of Grade3–4 mucositis (RR,0.97; 95% CI,0.74–1.26; p = 0.80), Grade 2–4 acute xerostomia (RR,0.35; 95%CI,0.02–5.44; p = 0.45), or late xerostomia (RR,0.40; 95%CI,0.13–1.24; p = 0.11) and Grade 3–4 dysphagia (RR,0.23; 95%CI,0.01–4.78; p = 0.35) was observed in patients treated with concomitant chemoradiotherapy. Compared with placebo or observation, amifostine does not show tumor protective effect in complete response (RR,1.02; 95%CI,0.89–1.17; p = 0.76) and partial response (RR,0.90; 95%CI, 0.56–1.44; p = 0.66). For the hematologic side effect, no statistical difference of Grade 3–4 leucopenia (RR,0.60; 95%CI,0.35–1.05; p = 0.07), anemia (RR,0.80; 95%CI, 0.42–1.53; p = 0.50) and thrombocytopenia (RR,0.43; 95%CI,0.16–1.15; p = 0.09) were found between amifostine and control groups. The most common amifostine related side effects were nausea, emesis, hypotension and allergic with an average incidence rate (Grade 3–4) of 5%, 6%, 4% and 4% respectively.ConclusionThis systematic review showed that amifostine significantly reduce the serious mucositis, acute/late xerastomia and dysphagia without protection of the tumor in HNSCC patients treated with radiotherapy. And the toxicities of amifostine were generally acceptable.

Research and Development of Radioprotective Agents: A Mini-Review

“…Amifostine is a sulfhydryl-containing compound. It is the only RA that has been approved by Food and Drug Administration of the USA [98] and the most commonly used RA in clinic, protecting the normal tissue via the scavenging of free radicals [99,100] . Having the characteristic of an ideal RA, it is of note that amifostine does not protect the tumor tissue [101] .…”

Paramètres de radiorésistance des cancers des voies aérodigestives supérieures et stratégies de radiosensibilisation

“…Cette molécule peut être administrée par voie veineuse ou souscutanée, mais seule l'administration intraveineuse a l'autorisation de mise sur le marché (AMM) en France [95]. Gu et al ont récem-ment publié une méta-analyse sur données publiées reprenant 17 essais sur 1167 patients étudiant les effets de l'amifostine dans l'irradiation dans cancers des voies aérodigestives supérieures [96]. En cas d'ajout de l'amifostine, ils ont montré une réduction du risque de mucite de grade 3-4 (risque relatif [RR] : 0,72 ; IC 95 % : 0,54-0,95, p < 0,00001), de xérostomie aiguë de grade 2-4 (RR : 0,70, IC 95 % : 0,52-0,96, p = 0,02), de xérostomie tardive de grade 2-4 (RR : 0,60, IC 95 % : 0,49-0,74, p < 0,00001) et de dysphagie de grade 3-4 (RR : 0,39, IC 95 % : 0,17-0,92, p = 0,03).…”

Clinical features and preventive therapies of radiation-induced xerostomia in head and neck cancer patient: a literature review

“…These authors stated that daily intravenous amifostine was associated with a high rate of serious adverse effects leading to discontinuation of the drug and sometimes delay in RT. Recent studies, however, have demonstrated that subcutaneous administration of amifostine was as effective as intravenous administration and safer considering toxicity [26,27]. Further research on the benefits of using subcutaneous amifostine is still required.…”