Abstract
Treatment-related adverse events (AEs) can obfuscate the maintenance of a conventional schedule of sunitinib in patients with metastatic renal cell carcinoma. Accordingly, alternative schedules seeking to improve the safety profile of sunitinib have been tested. Recently, two meta-analyses similarly described improved safety profiles favoring a two weeks on and one week off (2/1) schedule, but with conflicting results for survival outcomes. Therefore, we conducted an updated systematic review and meta-analysis, including all recently published studies and using complementary statistical methods. Endpoints included progression-free survival, overall survival, and AEs of 15 types. Eleven articles were included in this meta-analysis. Using adjusted findings, we noted statistically better results in progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.39–0.84; p = 0.005), but no difference in overall survival (hazard ratio, 0.66; 95% confidence interval, 0.42–1.04; p = 0.08). Moreover, the 2/1 schedule was beneficial for reducing the incidence of several AEs. Conclusively, our meta-analysis suggests that the 2/1 schedule holds promise as an alternative means of reducing AEs and maintaining patient quality of life. While the survival outcomes of the 2/1 schedule seem also to be favorable, the level of evidence for this was low, and the interpretation of these findings should warrant caution. Large scale randomized trials are needed to support these results.
Highlights
The therapeutic concept of metastatic renal cell carcinoma has been dramatically changed through the development of targeted therapies, which result in significant improvement of clinicalCancers 2019, 11, 1830; doi:10.3390/cancers11121830 www.mdpi.com/journal/cancersCancers 2019, 11, 1830 outcomes [1]
Treatment-related adverse events (AEs) can make it difficult to maintain the standard dosing schedule of sunitinib, AEs may cause a decrease in quality of life (QOL) for these patients, as well as an increase in costs due to concomitant medication or conservative treatment
The initial database search found 648 studies (363 in PubMed, 242 in EMBASE, and 43 in the Cochrane library); among them, studies remained after duplicates were removed
Summary
The therapeutic concept of metastatic renal cell carcinoma (mRCC) has been dramatically changed through the development of targeted therapies, which result in significant improvement of clinicalCancers 2019, 11, 1830; doi:10.3390/cancers11121830 www.mdpi.com/journal/cancersCancers 2019, 11, 1830 outcomes [1]. Sunitinib is an oral inhibitor of vascular endothelial growth factor (VEGF) receptors. 1, 2, and 3 as well as platelet-derived growth factor receptors. Sunitinib is currently used as the first choice in the treatment of mRCC, and it has been shown to increase progression-free survival (PFS). The standard dosing schedule for sunitinib is 50 mg once daily for four weeks on and two weeks off (4/2). In the original phase III trial, 38% and 32% of patients taking sunitinib experienced dose interruptions and reductions, respectively, due to secondary toxicity [2]. Treatment-related adverse events (AEs) can make it difficult to maintain the standard dosing schedule of sunitinib, AEs may cause a decrease in quality of life (QOL) for these patients, as well as an increase in costs due to concomitant medication or conservative treatment
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