Interferon-alpha Combined With Chemotherapy Versus Chemotherapy Alone For The Treatment Of Metastatic Melanoma:a Meta-Analysis

BackgroundMelanoma is a malignant tumor derived from neural crest melanocytes,with a high degree of malignancy and poor prognosis.The five-year survival rate for metastatic melanoma can be as low as 10%,and there is no effective treatment.Classic treatment methods relied on cytotoxic chemotherapy,which is limited by low response rates and significant adverse effects.Recent rapid advances in immunogenetics have led to a great progress of new systemic treatments for metastatic melanoma.Mmunotherapy has become the current research focus,and some scholars have found that immunotherapy combined with chemotherapy(ie,bio-chemotherapy)can improve the efficacy in metastatic melanoma.Although the results of some randomized controlled trials have not been consistent,many suggested that biochemotherapy is associated with an increased response rate,but has the disadvantage of increased toxicity.To obtain an unbiased and reliable assessment of the true benefit of interferon-alpha(IFN-?)combined with chemotherapy in metastatic melanoma,a meta-analysis of related randomized trials was performed.ObjectivesThe aim of this study was to compare the efficacy and safety of IFN-? combined with chemotherapy(experimental group)versus chemotherapy alone(control group)in metastatic melanoma.MethodsA systematic search for randomized controlled trials regarding IFN-? combined with chemotherapy in the treatment of metastatic melanoma was undertaken in PubMed,MEDLINE,EMBASE,the Cochrane Library,China HowNet,VIP Chinese scientific and technical journals,and Wanfang databases(from the databases were established to September 2016).Eligible articles were identified according to inclusion and exclusion criteria,and Meta-analysis was performed using RevMan 5.3.Combined relative risk(RR)and 95% confidence intervals(95% CIs)were calculated for response rates,survival rates and toxicity.ResultsA total of 14 randomized controlled trials were identified,including 1708 patients with metastatic melanoma,of which,897 patients were treated by IFN-?combined with chemotherapy,and 811 patients were treated by chemotherapy alone.Compared with chemotherapy alone,IFN-? combined with chemotherapy significantly increased the complete response rate(RR=2.97,95%CI=1.89-4.67,P<0.00001),the partial response rate(RR=1.31,95%CI=1.05-1.64,P=0.02)and the overall response rate(RR=1.59,95%CI=1.32-1.92,P<0.00001).It was indicated that IFN-? combined with chemotherapy does not significantly improve 1-year overall survival(RR=1.08,95%CI=0.90-1.30,P=0.39)and 3-year overall survival(RR=1.44,95%CI=0.82-2.54,P=0.20).IFN-? combined with chemotherapy did not significantly increase grade?3 hematologic toxicity(RR=1.44,95%CI=0.63-3.28,P=0.38)and grade?3 nausea and vomiting(RR=1.03,95%CI=0.78-1.35,P=0.86),but increased grade ? 3 fever response(RR=4.06,95%CI 1.67-9.87,P=0.002).Conclusions1.This meta-analysis showed that IFN-? combined with chemotherapy may moderately improve the complete response rate,the partial response rate and the overall response rate,but has no significant effect on 1-year,3-year overall survival in metastatic malignant melanoma.2.IFN-? combined with chemotherapy doesn't significantly increase hematologic toxicity and nausea and vomiting,but increases the incidence of fever toxicity.