Sunitinib is an orally administered inhibitor of tyrosine kinases and has become the standard of care for many patients with metastatic renal cell carcinoma. Its use has been associated with renal toxicity in some patients. We report a patient with a metastatic clear-cell renal carcinoma who showed arterial hypertension, nephrotic syndrome and azotaemia 10 months after treatment with sunitinib....

Angiogenesis inhibition with agents targeting tyrosine kinases of vascular endothelial growth factor receptors is an established anticancer treatment, but is, unfortunately, frequently accompanied by systemic hypertension and cardiac toxicity. Whether vascular endothelial growth factor receptor antagonism also has adverse effects on the pulmonary and coronary circulations is presently unknown. ...

Purpose:Developing strategies to overcome resistance to sunitinib is a major challenge in human renal cell carcinoma (RCC). We hypothesized that sunitinib-induced tumor necrosis–associated hypoxia could interact with renal cancer stem cells in patients with metastatic RCC. Experimental Design: We studied tissue samples from 7 patients with primary metastatic RCC, before and after sunitinib trea...

BACKGROUND The US FDA and the EMA have approved seven agents for the treatment of renal cell carcinoma, primarily based on differences in progression-free survival (PFS). Because PFS is an arbitrary endpoint we hypothesized that an analysis would demonstrate the growth rate of tumors remained constant at the time of RECIST-defined disease progression. METHODS We previously estimated the growt...

BACKGROUND Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. METHODS In this randomized, double-blind, phase 3 trial, we assigned 615 patients with loc...

PURPOSE To evaluate the effects of sunitinib, a multitargeted tyrosine kinase inhibitor, on the QT interval in patients with cancer. EXPERIMENTAL DESIGN Patients received sunitinib loading doses (150-200 mg) on days 3 and 9 and maintenance doses (50 mg/d) on days 4 to 8. Moxifloxacin (day 1), placebo (day 2), and granisetron [with placebo (day 2) or sunitinib (days 3 and 9)] were also adminis...

Sunitinib is an oral multitargeted tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma, imatinibrefractory gastrointestinal stromal tumor, and advanced pancreatic neuroendocrine tumors. The current studies were conducted to characterize the pharmacokinetics, distribution, and metabolism of sunitinib after intravenous and/or oral administrations of [C]sunitinib ...

BACKGROUND Increased exposure to multitargeted kinase inhibitor sunitinib is associated with improved outcome, emphasizing the importance of maintaining adequate dosing and drug levels. The currently approved schedule (50 mg daily, four weeks on, two weeks off) precludes further dose-intensification. Recent data suggest that sunitinib, although initially developed as an antiangiogenic agent, ha...

OBJECTIVE This study aims to investigate biological behavior changes in a murine lung cancer cell characterized by acquired resistance to sunitinib, a potent inhibitor of multiple-targeted receptor tyrosine kinase. METHODS A lung cancer cell line resistant to sunitinib (LL/2-R) was developed from its parental cell line (LL/2-P). Differences in biological characteristics and associated molecul...

BACKGROUND Activated proximal tubular cells play an important role in renal fibrosis. We investigated whether sunitinib and a kidney-targeted conjugate of sunitinib were capable of attenuating fibrogenic events in tubulointerstitial fibrosis. METHODS A kidney-targeted conjugate was prepared by linkage of a sunitinib analog (named 17864) via a platinum-based linker to the kidney-specific carri...