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Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Safety of Multi-Targeted Kinase Inhibitors as Monotherapy Treatment of Cancer: A Systematic Review of the Literature

Author(s): Sheila Crean, Dylan M. Boyd, Brian Sercus and Michael Lahn

Volume 4 , Issue 2 , 2009

Page: [143 - 154] Pages: 12

DOI: 10.2174/157488609788173026

Price: $65

Abstract

Purpose: To identify potential safety profiles for small molecule multi-targeted kinase inhibitors for the treatment of advanced cancer. Methods: A systematic review was performed on published papers and meeting abstracts reporting safety outcomes in cancer patients for selected multi-kinase inhibiting small molecules with mainly anti-angiogenic activity. Specifically, we focused on single agent safety or early phase clinical development studies. Results: Of 1,923 studies identified in a MEDLINE search, 26 primary studies met eligibility criteria. Meeting materials included 7 papers, 6 posters, and 27 abstracts. When grade I – IV safety results of all 23 kinases were summed together, diarrhea, fatigue, nausea, rash, anorexia, vomiting, hand/foot syndrome, and hypertension were common, occurring in greater than 10% of patients. When only grade III and IV events are pooled together, fatigue and hypertension remain relatively common ( > 5%). When total adverse events were stratified by kinase or by kinase family, differences in safety profiles emerged. Conclusions: The results of this systematic review suggest that adverse events are common and varied for patients treated with a multi-kinase inhibitor. However, unlike some systemic cytotoxic therapies, serious and severe adverse events for multikinase inhibitors are less frequent. Sub-analyses by target kinase or kinase family demonstrate that certain groups of multi-kinase inhibitors can be associated with different safety profiles with unique adverse events.

Keywords: Kinase Inhibitors, safety, phase 1 studies


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