Tannir Nizar M, Cohen Lorenzo, Wang Xuemei, Thall Peter, Mathew Paul F, Jonasch Eric, Siefker-Radtke Arlene, Pagliaro Lance C, Ng Chaan S, Logothetis Christopher
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2006 Nov 1;107(9):2254-61. doi: 10.1002/cncr.22253.
In vivo data have shown a more potent antiangiogenic effect and a higher antitumor activity of low-dose interferon (IFN) given twice daily. In a randomized Phase II trial, the authors tested the hypothesis that twice-daily low-dose IFN is more effective than daily intermediate-dose IFN in patients with metastatic renal cell cancer (MRCC).
A total of 118 patients (59 per arm) were randomly assigned to receive IFN at a dose of 0.5 million units (MU) given subcutaneously twice daily (IFN1) or IFN at a dose of 5 MU given subcutaneously daily (IFN5). The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR), overall survival (OS), toxicity, and quality of life (QOL).
There were no significant differences in either PFS or OS between IFN1 and IFN5 (median of 3.7 months and median of 3.4 months PFS, respectively; median of 25.5 months and median of 17.5 months OS, respectively). The RRs were identical in the 2 arms (6.7%; 95% confidence interval [95% CI], 1.8-16.5%). Two patients, 1 in each arm, remained in complete remission at the time of last follow-up, at 45+ and 38+ months from treatment. Thirty-two patients receiving IFN5 and 19 patients receiving IFN1 experienced Grade 3 or higher adverse events (graded using the National Cancer Institute Common Toxicity Criteria [version 2.0]) (P = .025). Eighteen patients receiving IFN5 and 4 patients receiving IFN1 had dose reductions (P = .002). There was a significant deterioration in QOL and an increase in depression associated with IFN5 but no change was noted with IFN1.
Compared with IFN5, IFN1 is neither more nor less effective but is less toxic, with a better reported QOL. These results may have implications for the design of combination regimens incorporating IFN with targeted agents.
体内数据显示，每日两次给予低剂量干扰素（IFN）具有更强的抗血管生成作用和更高的抗肿瘤活性。在一项随机II期试验中，作者检验了以下假设：对于转移性肾细胞癌（MRCC）患者，每日两次给予低剂量IFN比每日给予中等剂量IFN更有效。
总共118例患者（每组59例）被随机分配，分别接受皮下注射剂量为100万单位（MU）的IFN，每日两次（IFN1），或皮下注射剂量为5 MU的IFN，每日一次（IFN5）。主要终点为无进展生存期（PFS）。次要终点包括缓解率（RR）、总生存期（OS）、毒性和生活质量（QOL）。
IFN1和IFN5之间的PFS和OS均无显著差异（PFS中位数分别为3.7个月和3.4个月；OS中位数分别为25.5个月和17.5个月）。两组的RR相同（6.7%；95%置信区间[95%CI]，1.8 - 16.5%）。在最后一次随访时，每组各有1例患者仍处于完全缓解状态，分别为治疗后45 +个月和38 +个月。32例接受IFN5治疗的患者和19例接受IFN1治疗的患者发生3级或更高等级的不良事件（使用美国国立癌症研究所通用毒性标准[第2.0版]分级）（P = 0.025）。18例接受IFN5治疗的患者和4例接受IFN1治疗的患者进行了剂量减少（P = 0.002）。IFN5与生活质量显著恶化和抑郁增加相关，但IFN1未观察到变化。
与IFN5相比，IFN1疗效相当，但毒性较小，生活质量报告较好。这些结果可能对将IFN与靶向药物联合应用的方案设计有启示。
