Sunitinib: A Multitargeted Receptor Tyrosine Kinase Inhibitor in the Era of Molecular Cancer Therapies.
| Title: | Sunitinib: A Multitargeted Receptor Tyrosine Kinase Inhibitor in the Era of Molecular Cancer Therapies. |
|---|---|
| Authors: | Papaetis, Georgios S.1, Syrigos, Kostas N.1 |
| Source: | BioDrugs. 2009, Vol. 23 Issue 6, p377-389. 13p. 1 Diagram, 2 Charts. |
| Subject Terms: | *CARDIOVASCULAR agents, *PROTEIN-tyrosine kinases, *VASCULAR endothelial growth factors, *DRUG side effects, *RENAL cell carcinoma, *GASTROINTESTINAL stromal tumors |
| Abstract: | Sunitinib is an oral oxindole multitargeted kinase inhibitor that inhibits certain receptor tyrosine kinases (RTKs). These include vascular endothelial growth factor receptors (VEGFR type 1 and 2), platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), stem cell factor receptor (KIT), FMS-like tyrosine kinase-3 (FLT3), glial cell-line derived neurotrophic factor receptor (RET) and the receptor of macrophage-colony stimulating factor (CSF1R). Examination of the antitumor effect of sunitinib in a variety of cell lines in vitro suggested an antiproliferative activity that is dependent on the presence of constitutively active RTK targets. The use of sunitinib as first-line therapy in advanced renal cell carcinoma (RCC) has improved the overall survival compared with that observed after cytokine therapy, while its administration in patients with gastrointestinal stromal tumors (GISTs) after progression or intolerance to imatinib achieved an objective response of 7%. Sunitinib is currently approved for the treatment of GISTs in this setting, and as first-line therapy for the treatment of advanced RCC. The relatively long half-life of sunitinib and its major metabolite allow for a once-daily dosing schedule. An interesting antitumor activity of sunitinib was reported in phase II studies of patients with a variety of malignancies, such as hepatocellular cancer, pancreatic neuro-endocrine tumors, and non-small cell lung cancer; results of phase III studies are urgently anticipated. Fatigue is one of the most common adverse effects of sunitinib, as 50-70% of patients with advanced RCC and GIST complained of this adverse effect. Other adverse effects are diarrhea, anorexia, nausea and vomiting, oral changes and bleeding events. Most toxicities are reversible and should not result in discontinuation of sunitinib. If necessary, dose adjustments or interruptions should be made. Hypothyroidism has been described in the first 2 weeks of sunitinib therapy and its incidence increases progressively with the duration of therapy. Sunitinib may exert its hypertensive activity through a direct effect on the vasculature, while its most important cardiac adverse effect is left ventricular dysfunction. A variety of skin adverse effects have been described with the use of sunitinib such as hand-foot syndrome, yellow discoloration of the skin, dry skin, subungual splinter hemorrhages, acral erythema, and generalized skin rashes. Administration of sunitinib in the adjuvant and neoadjuvant setting of patients with RCC and of its combination with chemotherapy and other targeted therapies are currently under intense investigation. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Sunitinib: A Multitargeted Receptor Tyrosine Kinase Inhibitor in the Era of Molecular Cancer Therapies. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Papaetis%2C+Georgios+S%2E%22">Papaetis, Georgios S.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Syrigos%2C+Kostas+N%2E%22">Syrigos, Kostas N.</searchLink><relatesTo>1</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22BioDrugs%22">BioDrugs</searchLink>. 2009, Vol. 23 Issue 6, p377-389. 13p. 1 Diagram, 2 Charts. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22CARDIOVASCULAR+agents%22">CARDIOVASCULAR agents</searchLink><br />*<searchLink fieldCode="DE" term="%22PROTEIN-tyrosine+kinases%22">PROTEIN-tyrosine kinases</searchLink><br />*<searchLink fieldCode="DE" term="%22VASCULAR+endothelial+growth+factors%22">VASCULAR endothelial growth factors</searchLink><br />*<searchLink fieldCode="DE" term="%22DRUG+side+effects%22">DRUG side effects</searchLink><br />*<searchLink fieldCode="DE" term="%22RENAL+cell+carcinoma%22">RENAL cell carcinoma</searchLink><br />*<searchLink fieldCode="DE" term="%22GASTROINTESTINAL+stromal+tumors%22">GASTROINTESTINAL stromal tumors</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Sunitinib is an oral oxindole multitargeted kinase inhibitor that inhibits certain receptor tyrosine kinases (RTKs). These include vascular endothelial growth factor receptors (VEGFR type 1 and 2), platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), stem cell factor receptor (KIT), FMS-like tyrosine kinase-3 (FLT3), glial cell-line derived neurotrophic factor receptor (RET) and the receptor of macrophage-colony stimulating factor (CSF1R). Examination of the antitumor effect of sunitinib in a variety of cell lines in vitro suggested an antiproliferative activity that is dependent on the presence of constitutively active RTK targets. The use of sunitinib as first-line therapy in advanced renal cell carcinoma (RCC) has improved the overall survival compared with that observed after cytokine therapy, while its administration in patients with gastrointestinal stromal tumors (GISTs) after progression or intolerance to imatinib achieved an objective response of 7%. Sunitinib is currently approved for the treatment of GISTs in this setting, and as first-line therapy for the treatment of advanced RCC. The relatively long half-life of sunitinib and its major metabolite allow for a once-daily dosing schedule. An interesting antitumor activity of sunitinib was reported in phase II studies of patients with a variety of malignancies, such as hepatocellular cancer, pancreatic neuro-endocrine tumors, and non-small cell lung cancer; results of phase III studies are urgently anticipated. Fatigue is one of the most common adverse effects of sunitinib, as 50-70% of patients with advanced RCC and GIST complained of this adverse effect. Other adverse effects are diarrhea, anorexia, nausea and vomiting, oral changes and bleeding events. Most toxicities are reversible and should not result in discontinuation of sunitinib. If necessary, dose adjustments or interruptions should be made. Hypothyroidism has been described in the first 2 weeks of sunitinib therapy and its incidence increases progressively with the duration of therapy. Sunitinib may exert its hypertensive activity through a direct effect on the vasculature, while its most important cardiac adverse effect is left ventricular dysfunction. A variety of skin adverse effects have been described with the use of sunitinib such as hand-foot syndrome, yellow discoloration of the skin, dry skin, subungual splinter hemorrhages, acral erythema, and generalized skin rashes. Administration of sunitinib in the adjuvant and neoadjuvant setting of patients with RCC and of its combination with chemotherapy and other targeted therapies are currently under intense investigation. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of BioDrugs is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.2165/11318860-000000000-00000 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 377 Subjects: – SubjectFull: CARDIOVASCULAR agents Type: general – SubjectFull: PROTEIN-tyrosine kinases Type: general – SubjectFull: VASCULAR endothelial growth factors Type: general – SubjectFull: DRUG side effects Type: general – SubjectFull: RENAL cell carcinoma Type: general – SubjectFull: GASTROINTESTINAL stromal tumors Type: general Titles: – TitleFull: Sunitinib: A Multitargeted Receptor Tyrosine Kinase Inhibitor in the Era of Molecular Cancer Therapies. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Papaetis, Georgios S. – PersonEntity: Name: NameFull: Syrigos, Kostas N. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 11 Text: 2009 Type: published Y: 2009 Identifiers: – Type: issn-print Value: 11738804 Numbering: – Type: volume Value: 23 – Type: issue Value: 6 Titles: – TitleFull: BioDrugs Type: main |
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