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Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials.

Gu J, Zhu S, Li X, Wu H, Li Y, Hua F - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Forest plot of mucositis in HNSCC patients treated with radiotherapy/concomitant chemoradiation.The squares and horizontal lines demonstrate the study-specific OR and 95% CI. The area of the squares reflects the study specific weight (inverse of the variance). The diamond represents the pooled OR and 95% CI.
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pone-0095968-g003: Forest plot of mucositis in HNSCC patients treated with radiotherapy/concomitant chemoradiation.The squares and horizontal lines demonstrate the study-specific OR and 95% CI. The area of the squares reflects the study specific weight (inverse of the variance). The diamond represents the pooled OR and 95% CI.

Mentions: Of the seventeen trials, 16[3], [5], [6], [31]–[43] evaluated the mucositis with evident heterogeneity between studies(I2 = 85%) (Figure 3). The meta-analysis was performed in the random-effect model (Dersimonian-Laird method). Pooled analysis showed that amifostine reduced 28% of Grade 3–4 mucositis (RR,0.72; 95% CI,0.54–0.95; p<0.00001) indicating it can significantly decrease the risk of developing serious mucositis in patients treat with radiation. The publication bias was not detected in this subset analysis by Egger's test (p = 0.20). Subgroup analysis was performed cording to different treatment regimens (concomitant chemoradiotherapy or radiotherapy only) and admifostine administration (intravenously in or subcutaneously). In the subgroup analysis, statistically significant reduction of mucositis by using of amifostine was observed in patients treat with radiation only (RR,0.49; 95%CI,0.30–0.78; p = 0.03) and delivered intravenously(RR,0.52; 95%CI,0.34–0.78; p = 0.002) but not in patients treated with concurrent chemoradiation (RR,0.97; 95%CI,0.74–1.26; p = 0.80) and administered subcutaneously (RR,1.09; 95%CI,0.94–1.27; p = 0.24) (Table 2).


Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials.

Gu J, Zhu S, Li X, Wu H, Li Y, Hua F - PLoS ONE (2014)

Forest plot of mucositis in HNSCC patients treated with radiotherapy/concomitant chemoradiation.The squares and horizontal lines demonstrate the study-specific OR and 95% CI. The area of the squares reflects the study specific weight (inverse of the variance). The diamond represents the pooled OR and 95% CI.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4008569&req=5

pone-0095968-g003: Forest plot of mucositis in HNSCC patients treated with radiotherapy/concomitant chemoradiation.The squares and horizontal lines demonstrate the study-specific OR and 95% CI. The area of the squares reflects the study specific weight (inverse of the variance). The diamond represents the pooled OR and 95% CI.
Mentions: Of the seventeen trials, 16[3], [5], [6], [31]–[43] evaluated the mucositis with evident heterogeneity between studies(I2 = 85%) (Figure 3). The meta-analysis was performed in the random-effect model (Dersimonian-Laird method). Pooled analysis showed that amifostine reduced 28% of Grade 3–4 mucositis (RR,0.72; 95% CI,0.54–0.95; p<0.00001) indicating it can significantly decrease the risk of developing serious mucositis in patients treat with radiation. The publication bias was not detected in this subset analysis by Egger's test (p = 0.20). Subgroup analysis was performed cording to different treatment regimens (concomitant chemoradiotherapy or radiotherapy only) and admifostine administration (intravenously in or subcutaneously). In the subgroup analysis, statistically significant reduction of mucositis by using of amifostine was observed in patients treat with radiation only (RR,0.49; 95%CI,0.30–0.78; p = 0.03) and delivered intravenously(RR,0.52; 95%CI,0.34–0.78; p = 0.002) but not in patients treated with concurrent chemoradiation (RR,0.97; 95%CI,0.74–1.26; p = 0.80) and administered subcutaneously (RR,1.09; 95%CI,0.94–1.27; p = 0.24) (Table 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus