Sunitinib in the treatment of metastatic renal cell carcinoma

Abstract

Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy. Sunitinib alone causes significant side effects and has a distinct profile with diarrhoea, hypertension, skin effects hypothyroidism, fatigue and nausea of special interest. The recommended dose of sunitinib in mRCC is 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment (4/2 schedule). An alternative 2 weeks on, 1 week off schedule (2/1 schedule) seems to be of similar efficacy and better tolerability and could be more widely used in the future. An intermittent treatment strategy with a stop in remission and re-induction after progression showed efficacy in smaller trials and is currently being evaluated in a phase III trial. Direct comparison of sunitinib with pazopanib in first-line treatment showed a similar efficacy for both TKIs with a distinct toxicity profile. Data from two phase II trials showed that sunitinib has also activity in non-clear cell cancer and is an option due to a lack of better alternatives. Currently, after immune checkpoint inhibitors have shown very promising results in the second-line treatment of RCC, they are being tested in a number of phase III trials in the first-line setting. The future will show the position of sunitinib in the first-line treatment of RCC in the era of the immune checkpoint inhibitors.

EIF3D promotes sunitinib resistance of renal cell carcinoma by interacting with GRP78 and inhibiting its degradation

“…Sunitinib is a molecular targeted therapy drug used as the firstline chemotherapy agent for metastatic RCC [4] . Sunitinib works as a multi-targeted tyrosine-kinase inhibitor whose targets include vascular endothelial growth factor (VEGF) receptors, stem cell growth factor receptor (KIT), Platelet-derived growth factor receptor (PDGFR) and macrophage colony-stimulating factor receptor (MCSFR) [ 4 , 5 ].…”

Modulating ATP binding cassette transporters in papillary renal cell carcinoma type 2 enhances its response to targeted molecular therapy

“…Our data indicate that in pure PRCC2 biology, everolimus does show better chemopreventative effect than sunitinib. Two previous trials (ASPEN and ESPN) have attempted to compare between sunitinib and everolimus treatment in PRCCs (Armstrong et al, 2016;Schmid and Gore, 2016;Tannir et al, 2016). In both the ASPN and ESPN trials, no attempt was made to subtype the PRCC patients or distinguish between the treatment arms in the specific PRCC subtypes.…”

Cancer Management by Tyrosine Kinase Inhibitors: Efficacy, Limitation, and Future Strategies

“…Combination of sunitinib with chemotherapy was not explored after phase I trials showing its poor safety profile [81]. Trials combining sunitinib with other therapies have also shown no improved efficacy, yet increased toxicity [82]. On the other hand, Sorafenib was also proven to have high clinical efficacy against mRCC, both as firstand second-line therapy [83].…”