Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials.
BACKGROUND
Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent.


METHODS
By 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.


RESULTS
Seventeen 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 Grade 3-4 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 Grade 3-4 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.


CONCLUSIONS
This 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.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China; Department of Oncology, Tianjin Union Medical Center, Tianjin, China.
Jundong
J
Gu
Department of Oncology, Tianjin Union Medical Center, Tianjin, China.
Siwei
S
Zhu
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Xuebing
X
Li
Department of Human resources, Tianjin Union Medical Center, Tianjin, China.
Hua
H
Wu
Department of obstetrics and gynecology, Tianjin Hospital of Tianjin City, Tianjin, China.
Yang
Y
Li
Department of surgery oncology, Shandong cancer hospital, Jinan, China.
Feng
F
Hua
D004999:Amifostine / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D011832:Radiation Injuries / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck
D004999:Amifostine