Hernberg M, Pyrhönen S, Muhonen T
Department of Oncology, Helsinki University Central Hospital, Finland.
J Immunother. 1999 Mar;22(2):145-54. doi: 10.1097/00002371-199903000-00006.
The effect of interferon-alpha (IFN-alpha) as single agent or in combination in the treatment of metastatic malignant melanoma (MM) or of advanced renal cell carcinoma (RCC) has been widely explored in phase II trials. To evaluate the net benefit of IFN-alpha therapy in these diseases, we performed a meta-analysis comprising all available randomized trials comparing regimens with or without IFN-alpha. Data were obtained from the Medline data base, and from the data bases at the National Cancer Institute, Schering-Plough, and Hoffmann-La Roche. A total of six published and five unpublished studies on metastatic MM, as well as six published and two unpublished studies on advanced RCC, comprising altogether 1,164 and 525 patients, respectively, fulfilled our criteria. In MM, the overall response rate for the IFN-alpha-containing regimens was 24% (range, 10-46%), compared with 17% (range, 5-30%) for those without IFN-alpha. In RCC, the overall response rate for IFN-alpha-containing regimens was 14% (range, 4-33%), and 8% (range, 3-27%) for those without IFN-alpha. A meta-analysis showed that regimens including IFN-alpha improved response rates compared with regimens without IFN-alpha. The pooled odds ratio (OR) for improved response with IFN-alpha in metastatic MM was 0.65 [95% confidence interval (CI) 0.48 to 0.87], and in advanced RCC the OR was 0.47 (95% CI 0.26-0.85). In five metastatic MM trials and three RCC trials, enough data on survival were reported to estimate a pooled 1-year OR for survival. The pooled OR for improved survival with IFN-alpha was 0.69 (95% CI 0.50-0.94), and 0.46 (95% CI 0.28-0.75), respectively. The data on both metastatic MM and advanced RCC indicate that better response rates and prolonged survival can be achieved with regimens including IFN-alpha. The clinical relevance of these findings will be discussed.
在II期试验中，已广泛探索了α干扰素（IFN-α）作为单一药物或联合用药治疗转移性恶性黑色素瘤（MM）或晚期肾细胞癌（RCC）的效果。为评估IFN-α治疗这些疾病的净效益，我们进行了一项荟萃分析，纳入了所有比较含或不含IFN-α方案的现有随机试验。数据来自Medline数据库以及美国国立癌症研究所、先灵葆雅公司和罗氏公司的数据库。共有6项已发表和5项未发表的关于转移性MM的研究，以及6项已发表和2项未发表的关于晚期RCC的研究符合我们的标准，这些研究分别共纳入了1164例和525例患者。在MM中，含IFN-α方案的总体缓解率为24%（范围为10%-46%），而不含IFN-α方案的总体缓解率为17%（范围为5%-30%）。在RCC中，含IFN-α方案的总体缓解率为14%（范围为4%-33%），不含IFN-α方案的总体缓解率为8%（范围为3%-27%）。一项荟萃分析表明，与不含IFN-α的方案相比，含IFN-α的方案提高了缓解率。在转移性MM中，使用IFN-α改善缓解的合并比值比（OR）为0.65[95%置信区间（CI）为0.48至0.87]，在晚期RCC中，OR为0.47（95%CI为0.26 - 0.85）。在5项转移性MM试验和3项RCC试验中，报告了足够的生存数据以估计合并的1年生存OR。使用IFN-α改善生存的合并OR分别为0.69（95%CI为0.50 - 0.94）和0.46（95%CI为0.28 - 0.75）。转移性MM和晚期RCC的数据均表明，含IFN-α的方案可实现更好的缓解率和更长的生存期。将讨论这些发现的临床相关性。
