Clinica Chirurgica Generale 2, Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
J Natl Cancer Inst. 2010 Apr 7;102(7):493-501. doi: 10.1093/jnci/djq009. Epub 2010 Feb 23.
Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS).
We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided.
The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression.
In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.
基于以前对随机对照试验（RCT）的荟萃分析，干扰素 alpha（IFN-alpha）在辅助治疗中可改善高危皮肤黑色素瘤患者的无病生存期（DFS）。然而，RCT 对 IFN-alpha 对总生存期（OS）的影响产生了相互矛盾的数据。
我们进行了系统评价和荟萃分析，以检查 IFN-alpha 对高危皮肤黑色素瘤患者 DFS 和 OS 的影响。系统评价通过搜索 MEDLINE、EMBASE、Cancerlit、Cochrane、ISI Web of Science 和 ASCO 数据库进行。荟萃分析使用时间事件数据，从中估计 DFS 和 OS 的危险比（HR）和 95%置信区间（CI）。还进行了亚组和荟萃回归分析，以研究剂量和治疗持续时间的影响。统计检验为双侧。
荟萃分析包括 1990 年至 2008 年期间发表的 14 项 RCT，涉及 8122 名患者，其中 4362 名患者被分配到 IFN-alpha 组。在 14 项试验中的 12 项中，IFN-alpha 单独与观察进行比较，总共产生了 17 项比较（IFN-alpha 与比较剂）。IFN-alpha 治疗与 17 项比较中的 10 项（疾病复发的 HR = 0.82，95%CI = 0.77 至 0.87；P <.001）和 14 项比较中的 4 项（死亡的 HR = 0.89，95%CI = 0.83 至 0.96；P =.002）的 DFS 有统计学意义的改善。在 DFS 和 OS 中均未观察到研究间的异质性。亚组分析和荟萃回归未确定最佳 IFN-alpha 剂量和/或治疗持续时间或对辅助治疗更敏感的亚组患者。
在高危皮肤黑色素瘤患者中，IFN-alpha 辅助治疗在 DFS 和 OS 方面均显示出统计学意义的改善。
