Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma

2020 ◽  
Vol 16 (28) ◽  
pp. 2147-2164
Author(s):  
Allen Jacob ◽  
Jaret Shook ◽  
Thomas E Hutson
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinases ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Vegf Receptor ◽  
Vegf Receptors ◽  
Orally Bioavailable

The VHL mutation– HIF upregulation– VEGF transcription sequence is the principal pathway in the development of renal cell carcinoma. Tyrosine kinase inhibitors target the VEGF receptors to inhibit further growth of renal cell carcinoma tumors. Tivozanib, originally named AV-951 and KRN-951, is a novel, orally bioavailable VEGF tyrosine kinase inhibitor that is selective for VEGF receptors 1, 2 and 3. Further, only picomolar concentrations of tivozanib are required to target these VEGF receptors and prevent phosphorylation; this potency prevents the debilitating side effects that occur with treatments whose mechanisms of action involve broad-spectrum tyrosine kinase inhibition. This review summarizes the growing body of evidence supporting tivozanib's efficacy and safety in the treatment of advanced renal cell carcinoma.

Risk of toxicity with immunotherapy–tyrosine kinase inhibitors for metastatic renal cell carcinoma: a meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Matteo Santoni ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Relative Risks

Aim: Few data are available regarding the safety profile of immunotherapy–tyrosine kinase inhibitor (IO-TKI) combinations in metastatic renal cell carcinoma. The authors investigated all-grade and grade 3–4 (G3–4) adverse events in trials comparing IO-TKI combinations with sunitinib monotherapy. Methods: The relative risks of several all-grade and G3–4 adverse events were analyzed. Results: Relative risks were similar between patients receiving IO-TKI combinations versus sunitinib monotherapy. However, the use of IO-TKI combinations was associated with a higher risk of all-grade and G3–4 diarrhea, all-grade hypothyroidism, G3–4 decreased appetite, all-grade and G3–4 aspartate transaminase increase and all-grade and G3–4 alanine transaminase increase. Conclusion: The results of the authors' meta-analysis suggest that risks of treatment-related adverse events should be carefully considered when choosing IO-TKI combinations in metastatic renal cell carcinoma patients.

Sunitinib induced colitis manifesting as invasive diarrhea in a patient with renal cell carcinoma

2021 ◽  
pp. 107815522110611
Author(s):  
Yasemin Gündoğdu ◽  
Orhan Cem Deniz ◽  
Didem Saka ◽  
Gürhan Şişman ◽  
Sibel Erdamar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Normal Mucosa ◽  
Drug Induced ◽  
Pathologic Findings

Introduction Sunitinib is a tyrosine kinase inhibitor that binds to vascular endothelial factor receptor currently used for the treatment of renal cell carcinoma, as well as for several other conditions such as gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. We present a patient with invasive diarrhea who was treated with sunitinib for metastatic renal cell carcinoma. Case report Drug induced colitis was confirmed with colonoscopy from histopathological specimens. Clinical recovery of diarrhea was achieved with oral budesonide. Remarkably, the pathologic findings were observed in both the macroscopically normal mucosa and the mucosa with aphthous ulcers in the colon. Management & outcome The patient was treated for sunitinib associated diarrhea, after exclusion of the other reasons. Metronidazole and piperacillin/tazobactam treatment were prescribed. Discussion Diarrhea is a frequent symptom in patients treated with tyrosine kinase inhibitors, however the described pathologic findings have rarely been reported. Our aim is to emphasize the importance of close follow-up in patients treated with tyrosine kinase inhibitors, and to raise awareness on the management of sunitinib induced colitis.

Real-world chart review study of adverse events management in patients taking tyrosine kinase inhibitors to treat metastatic renal cell carcinoma

2017 ◽  
Vol 24 (8) ◽  
pp. 574-583 ◽  
Author(s):  
Sandy Srinivas ◽  
Dara Stein ◽  
Dana Y Teltsch ◽  
Sunning Tao ◽  
Laura Cisar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Metastatic Renal Cell Carcinoma ◽  
Special Interest ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor

Purpose The purpose is to describe management of adverse events of special interest across tyrosine kinase inhibitors approved for metastatic renal cell carcinoma. Methods We conducted a retrospective chart review in metastatic renal cell carcinoma patients initiating tyrosine kinase inhibitor monotherapy between 15 November 2010 and 15 November 2013, and experiencing ≥ 1 adverse events of special interest (diarrhea, fatigue, hand-foot syndrome, hypertension, or stomatitis/mucositis) within 3 months of initiation. Demographics, medical history, treatment regimens, and adverse events of special interest management data for 3.5 months postonset were collected. Results In 220 charts from 27 centers, tyrosine kinase inhibitors prescribed included sunitinib (55%), pazopanib (27%), axitinib (9%), and sorafenib (8%). During the study period, patients experienced 376 adverse events of special interest (13% serious). Fatigue was most common (62% of patients), followed by hypertension (37%), diarrhea (30%), stomatitis/mucositis (29%), and hand-foot syndrome (12%). Over half (56%) the adverse events of special interest were resolved or resolving. Treatment discontinuation due to adverse events of special interest occurred in 15% of patients. Prophylaxis was rarely provided (8%), whereas 59% of patients received adverse events of special interest treatment (pharmacologic (55%) and/or nonpharmacologic (7%)), 27% received tyrosine kinase inhibitor dose management, 23% received both adverse events of special interest treatment and dose management, and 31% received neither. Hypertension was the most treated (72% of all events), and fatigue was the least treated (9%); only 4% of patients received pharmacologic treatment for fatigue. Conclusions Most adverse events of special interest were nonserious and more than half of the patients received pharmacologic and/or nonpharmacologic treatment. Fatigue was the most common yet least frequently treated adverse event of special interest, and few patients received prophylaxis or nonpharmacologic treatment. More emphasis on treatment and prophylaxis options for bothersome adverse events is warranted.

scholarly journals Pharmacotherapy Options in Advanced Renal Cell Carcinoma: What Role for Pazopanib?

2011 ◽  
Vol 5 ◽  
pp. CMO.S6087 ◽  
Author(s):  
Michael R. Harrison
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Tumor Biology ◽  
Mammalian Target Of Rapamycin

Over the last 6 years, the treatment of metastatic renal cell carcinoma (mRCC) has undergone dramatic changes. A better understanding of the pathogenesis and tumor biology of sporadic renal cell carcinoma has led to the approval of 6 drug regimens: 3 oral multi-targeted tyrosine-kinase inhibitors (sorafenib, sunitinib, and pazopanib), 2 inhibitors of the mammalian target of rapamycin (temsirolimus and everolimus), and 1 monoclonal antibody against the vascular endothelial growth factor (bevacizumab). Pazopanib, a multi-targeted tyrosine kinase inhibitor that targets VEGFR-1, -2, and-3; PDGFR-α and PDGFR-β, and c-Kit, was approved for the treatment of mRCC in October 2009, several years after the other drugs in its class. The efficacy and safety of pazopanib in Phase I, II, and III trials will be examined and its role in mRCC treatment will be described. Future studies that may clarify pazopanib's role in mRCC will be discussed. Based on pazopanib's demonstrated efficacy in treatment-naïve and cytokine-refractory patients, along with a seemingly favorable toxicity profile compared with other multi-targeted tyrosine-kinase inhibitors, pazopanib may have a unique niche in the armamentarium of treatment options for mRCC. Results from ongoing studies are awaited to confirm pazopanib's favorable efficacy-toxicity ratio, especially in comparison with the previous first-line standard-of-care, sunitinib.

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