Table_2_A 2/1 Sunitinib Dosing Schedule Provides Superior Antitumor Effectiveness and Less Toxicity Than a 4/2 Schedule for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.DOCX

Background: The standard sunitinib schedule to treat metastatic renal cell carcinoma (mRCC) is 4 weeks on/2 weeks off (4/2). However, some studies revealed intolerable adverse events (AEs) in patients on this schedule. An alternative schedule, 2 weeks on/1 week off (2/1), may overcome this issue. This meta-analysis was performed to compare the effectiveness and toxicity between the 2/1 and 4/2 sunitinib dosing schedules.
Methods: We acquired relevant studies by searching PubMed, ScienceDirect, the Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar. Our main endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and AEs.
Results: We identified 9 medium- and high-quality studies. Both schedules were effective for mRCC, with comparable OS and similar ORR. However, the 2/1 schedule had better PFS (hazard ratio (HR) = 0.81, 95% confidence interval [CI]: 0.66–0.99, P = 0.04), higher DCR [risk rate (RR) = 1.22, 95% CI: 1.01–1.47, P = 0.04] and fewer dosage interruptions (RR = 0.60, 95% CI: 0.43–0.84, P = 0.003). Additionally, the 2/1 schedule elicited fewer specific severe AEs, including thrombocytopenia/platelet disorder, hand-foot syndrome, hypertension, and fatigue. In our subanalysis, PFS was better among East Asians using the 2/1 schedule than among other populations (HR= 0.75, 95% CI: 0.58–0.98, P = 0.03), and patients administered an initial dosage of 50 mg/d on the 2/1 schedule had superior PFS (HR = 0.76, 95% CI: 0.59–0.97, P = 0.03) than those others.
Conclusions: These findings suggest that the 2/1 schedule is more suitable for mRCC than 4/2, due to superior PFS, better DCR and fewer AEs. Nevertheless, more large-scale studies with good quality are needed.

背景：治疗转移性肾细胞癌（metastatic renal cell carcinoma, mRCC）的标准舒尼替尼给药方案为4周给药/2周停药（4/2方案）。然而，部分研究显示该方案会使患者出现难以耐受的不良反应（adverse events, AEs）。作为替代方案，2周给药/1周停药（2/1方案）或可解决这一问题。本荟萃分析旨在对比2/1与4/2舒尼替尼给药方案的疗效与毒性反应。

方法：本研究通过检索PubMed、ScienceDirect、Cochrane图书馆、Scopus、Ovid MEDLINE、Embase、Web of Science及Google Scholar获取相关研究。本研究的主要终点包括总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）、客观缓解率（objective response rate, ORR）、疾病控制率（disease control rate, DCR）以及不良反应。

结果：最终纳入9项中高质量研究。两种给药方案均对转移性肾细胞癌有效，总生存期与客观缓解率相当。但2/1方案的无进展生存期更优（风险比（hazard ratio, HR）=0.81，95%置信区间（confidence interval, CI）：0.66~0.99，P=0.04），疾病控制率更高（风险率（risk rate, RR）=1.22，95%CI：1.01~1.47，P=0.04），且给药中断次数更少（RR=0.60，95%CI：0.43~0.84，P=0.003）。此外，2/1方案引发的特定严重不良反应更少，包括血小板减少症/血小板异常、手足综合征、高血压及疲劳。亚组分析显示，相较于其他人群，采用2/1方案的东亚患者无进展生存期更优（HR=0.75，95%CI：0.58~0.98，P=0.03）；且在2/1方案中，初始剂量为50mg/d的患者无进展生存期优于其他患者（HR=0.76，95%CI：0.59~0.97，P=0.03）。

结论：本研究结果表明，相较于4/2方案，2/1方案更适用于转移性肾细胞癌的治疗，因其无进展生存期更优、疾病控制率更高且不良反应更少。不过，仍需开展更多高质量的大规模研究加以验证。