Toxicity of sorafenib: clinical and molecular aspects.
BACKGROUND
Sorafenib is a novel oral bis-aryl urea compound originally developed as an inhibitor of RAF kinase for its anti-proliferative property. Sorafenib also inhibits receptor tyrosine kinases of multiple pro-angiogenic factors such as VEGFR-1/2/3, Flt-3 and PDGFR-beta. The combination of both its anti-proliferative and anti-angiogenic properties makes sorafenib an attractive agent in cancer treatment. Sorafenib has been approved for the treatment of metastatic renal cell carcinoma as well as hepatocellular cancer. Despite its inherent selectivity, sorafenib can cause unusual adverse events whose the management represents a challenge for oncologists.


METHODS
Relevant literature was identified using a Pubmed search of articles published up to June 2009. Search terms included 'sorafenib' and 'toxicity'. Original articles were reviewed and relevant citations from these articles were also considered.


RESULTS
The clinical aspect of sorafenib-induced adverse events and the molecular basis behind this toxicity are discussed. Finally, recommendations for the management of these adverse events are proposed.


CONCLUSIONS
Although not life-threatening, toxicity of sorafenib can severely impact the physical, psychological and social well-being of patients. The management of this unusual toxicity highlights the particular need of new pluridisciplinarities linking oncologist, cardiologist and dermatologist.
Blanchet
Benoit
B
Laboratoire de Pharmacologie-Toxicologie, Service de Pharmacie, GH Cochin-Saint Vincent-de-Paul, 75014 Paris, France. benoit.blanchet@cch.aphp.fr
Billemont
Bertrand
B
Barete
Stéphane
S
Garrigue
Hélène
H
Cabanes
Laure
L
Coriat
Romain
R
Francès
Camille
C
Knebelmann
Bertrand
B
Goldwasser
François
F
D000818:Animals; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000627:therapeutic use / Q000633:toxicity*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism; D002986:Clinical Trials as Topic; D005076:Exanthema / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use / Q000633:toxicity*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077157:Sorafenib; D048490:raf Kinases / Q000378:metabolism
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D048490:raf Kinases