AUTHOR=Deng Huan , Li Meng , Wu Qian , Wang Li , Hong Zhengdong , Yi Fengming , Wei Yiping , Zhang Wenxiong 

TITLE=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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00313

DOI=10.3389/fonc.2020.00313

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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, <italic>P</italic> = 0.04), higher DCR [risk rate (RR) = 1.22, 95% CI: 1.01–1.47, <italic>P</italic> = 0.04] and fewer dosage interruptions (RR = 0.60, 95% CI: 0.43–0.84, <italic>P</italic> = 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, <italic>P</italic> = 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, <italic>P</italic> = 0.03) than those others.</p><p><bold>Conclusions:</bold> 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.</p>