Abstract
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.
Highlights
As the second most common tumor in the urological system, kidney cancer is estimated to account for73,820 cancer cases and result in 14,770 deaths in 2019 [1, 2]
In a recent study at a major Comprehensive Cancer Center, Atkinson et al suggested that alternative schedules had superior progression-free survival (PFS) [hazard ratio (HR) = 0.49, 95% confidence interval [confidence intervals (CIs)]: 0.36–0.67, P < 0.0001] and better overall survival (OS) (HR = 0.48, 95% CI: 0.34–0.69, P < 0.0001) than traditional schedules [13]
Our pooled results of nine included studies demonstrated that there was no significant difference in OS and objective response rate (ORR), but the 2/1 schedule was associated with longer PFS, better disease control rate (DCR) and fewer drug interruptions
Summary
As the second most common tumor in the urological system, kidney cancer is estimated to account for820 cancer cases and result in 14,770 deaths in 2019 [1, 2]. A phase III randomized controlled trial (RCT) indicated that treatment on a 4/2 schedule had an improved PFS, higher response rates, and fewer adverse events (AEs) than interferon-alpha [7]. Base on these RCTs, 4 weeks on/2 weeks off (4/2) with a dosage of 50 mg/d is the traditional schedule for sunitinib [8]. Some sunitinib-related severe AEs from the 4/2 schedule led to poor tolerability and reduced health-related quality of life for some mRCC patients, so these AEs need to be monitored carefully [9] This problem requires further research in detail. This meta-analysis was performed to compare the effectiveness and toxicity between the 2/1 and 4/2 sunitinib dosing schedules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
