Sorafenib: a clinical and pharmacologic review.
BACKGROUND
Sorafenib is an oral receptor tyrosine kinase inhibitor that inhibits Raf serine/threonine kinases and receptor tyrosine kinases (vascular endothelial growth factor receptors 1, 2, 3 and platelet-derived growth factor-beta, Flt-3 and c-kit) that are implicated in tumorigenesis and tumor progression. Sorafenib is approved for the treatment of advanced inoperable hepatocellular cancer and advanced renal cell cancer.


METHODS
The findings from the major Phase III studies that led to FDA approval of this drug for the above indications are reviewed. Key aspects of sorafenib pharmacology, dosing in the presence of organ dysfunction, toxicities and weaknesses of the research done so far are summarized.


BACKGROUND
The reader will have the knowledge of the major studies that form the basis of the clinical use of sorafenib, information on the upcoming Phase III trials that could lead to changes in clinical practice and some insights on aspects of the drugs' mechanism of action and toxicity that still remain unclear.


CONCLUSIONS
Sorafenib is a well-tolerated oral antiangiogenic agent approved for treatment of two angiogenesis-driven cancers. Studies to broaden the clinical indications and increase understanding of the clinical and laboratory biomarkers of response are needed.
Iyer
Renuka
R
Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. renuka.iyer@roswellpark.org
Fetterly
Gerald
G
Lugade
Amit
A
Thanavala
Yasmin
Y
D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000331:legislation & jurisprudence; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib