Safety of multi-targeted kinase inhibitors as monotherapy treatment of cancer: a systematic review of the literature.
OBJECTIVE
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.
Crean
Sheila
S
United BioSource Corporation, 101 Station Landing, Medford, MA 02155, USA. sheila.crean@unitedbiosource.com
Boyd
Dylan M
DM
Sercus
Brian
B
Lahn
Michael
M
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors