Hu Bin, Zhou Quan, Wu Tao, Zhuang Lan, Yi Liping, Cao Jinxia, Yang Xin, Wang Jun
Int J Clin Pharmacol Ther. 2017 Apr;55(4):329-338. doi: 10.5414/CP202714.
We performed this meta-analysis to compare the efficacy and safety between two different administration routes of bortezomib, subcutaneous and intravenous.
Six retrospective studies and three randomized controlled trials (RCTs) were included in our study. Data from retrospective studies or RCTs were pooled and displayed in their corresponding subgroup, retrospective studies subgroup or RCTs subgroup. We comprehensively compared the overall response rate (ORR) and the incidence of adverse events between subcutaneous and intravenous bortezomib.
We did not find statistical difference in ORR between the two administration routes. The pooled RRs for ORR were 0.99 (95% CI = 0.79 - 1.25, p = 0.95; retrospective studies subgroup) and 1.02 (95% CI = 0.93 - 1.11, p = 0.69; RCTs subgroup). Compared with intravenous bortezomib, the subcutaneous bortezomib reduced the incidence of peripheral neuropathy, both any grade and grade ≥ 3. The pooled RRs for any grade of peripheral neuropathy were 0.33 (95% CI = 0.15 - 0.71, p = 0.004; retrospective studies subgroup) and 0.55 (95% CI = 0.31 - 0.97, p = 0.04; RCTs subgroup), and for peripheral neuropathy grade ≥ 3 were 0.40 (95% CI = 0.16 - 0.95, p = 0.04; retrospective trials subgroup) and 0.39 (95% CI = 0.19 - 0.80, p = 0.01; RCTs subgroup). Only retrospective trials subgroup found that the incidence of thrombocytopenia and renal and urinary disorders were lower in subcutaneous bortezomib than in intravenous, with the pooled RRs 0.46 (95% CI = 0.29 - 0.72, p = 0.0007; retrospective trials subgroup) and 0.23 (95% CI = 0.09 - 0.56, p = 0.001; retrospective trials subgroup), respectively. The RCTs subgroup did not find statistical differences in these two adverse events.
CONCLUSIONS: Subcutaneous bortezomib did not significantly reduce therapeutic efficacy but resulted in a lower incidence of peripheral neuropathy than intravenous bortezomib. Compared with intravenous bortezomib, subcutaneous bortezomib might reduce the incidence of thrombocytopenia and renal and urinary disorders, but this needs more clinical trials to confirm. .
我们进行这项荟萃分析以比较硼替佐米两种不同给药途径（皮下注射和静脉注射）的疗效和安全性。
我们的研究纳入了六项回顾性研究和三项随机对照试验（RCT）。回顾性研究或RCT的数据进行汇总并显示在相应亚组中，即回顾性研究亚组或RCT亚组。我们全面比较了皮下注射和静脉注射硼替佐米的总缓解率（ORR）以及不良事件的发生率。
我们未发现两种给药途径在ORR上存在统计学差异。ORR的合并相对危险度（RR）在回顾性研究亚组中为0.99（95%可信区间[CI]=0.79 - 1.25，p = 0.95），在RCT亚组中为1.02（95%CI = 0.93 - 1.11，p = 0.69）。与静脉注射硼替佐米相比，皮下注射硼替佐米降低了任何级别以及≥3级周围神经病变的发生率。任何级别周围神经病变的合并RR在回顾性研究亚组中为0.33（95%CI = 0.15 - 0.71，p = 0.004），在RCT亚组中为0.55（95%CI = 0.31 - 0.97，p = 0.04）；≥3级周围神经病变的合并RR在回顾性试验亚组中为0.40（95%CI = 0.16 - 0.95，p = 0.04），在RCT亚组中为0.39（95%CI = 0.19 - 0.80，p = 0.01）。仅回顾性试验亚组发现皮下注射硼替佐米的血小板减少症以及肾脏和泌尿系统疾病的发生率低于静脉注射，合并RR分别为0.46（95%CI = 0.29 - 0.72，p = 0.0007；回顾性试验亚组）和0.23（95%CI = 0.09 - 0.56，p = 0.001；回顾性试验亚组）。RCT亚组在这两种不良事件中未发现统计学差异。
皮下注射硼替佐米并未显著降低治疗效果，但导致周围神经病变的发生率低于静脉注射硼替佐米。与静脉注射硼替佐米相比，皮下注射硼替佐米可能降低血小板减少症以及肾脏和泌尿系统疾病的发生率，但这需要更多临床试验来证实。
