Sorafenib tosylate (CAS: 475207-59-1)

Medical uses

At the current time sorafenib is indicated as a treatment for advanced renal

cell carcinoma (RCC), unresectable hepatocellular carcinomas(HCC) and thyroid cancer.

Kidney cancer

An article in The New England Journal of Medicine, published January 2007, showed

compared with placebo, treatment with sorafenib prolongsprogression-free survival in

patients with advanced clear cell renal cell carcinoma in whom previous therapy has

failed. The median progression-free survival was 5.5 months in the sorafenib group

and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib

group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). A few reports described

patients with stage IV renal cell carcinomas that were successfully treated with a multimodal

approach including neurosurgical, radiation, and sorafenib. This is one of two TGA-labelled

indications for sorafenib, although it is not listed on the Pharmaceutical Benefits Scheme for

this indication.

Liver cancer

At ASCO 2007, results from the SHARP trial were presented, which showed efficacy of sorafenib

in hepatocellular carcinoma. The primary endpoint was median overall survival, which showed a

44% improvement in patients who received sorafenib compared to placebo (hazard ratio0.69; 95%

CI, 0.55 to 0.87; p=0.0001). Both median survival and time to progression showed 3-month improvements.

There was no difference in quality of life measures, possibly attributable to toxicity of sorafenib or

symptoms related to underlying progression of liver disease. Of note, this trial only included patients

with Child-Pugh Class A (i.e. mildest) cirrhosis. The results of the study appear in the July 24, 2008,

edition of The New England Journal of Medicine. Because of this trial Sorafenib obtained FDA

approval for the treatment of advanced hepatocellular carcinoma in November 2007.

In a randomized, double-blind, phase II trial combining sorafenib with doxorubicin, the median time

to progression was not significantly delayed compared with doxorubicin alone in patients with advanced

hepatocellular carcinoma. Median durations of overall survival andprogression-free survival were

significantly longer in patients receiving sorafenib plus doxorubicin than in those receiving doxorubicin

alone. A prospective single-centre phase II study which included the patients with unresectable hepatocellular

carcinoma (HCC)concluding that the combination of sorafenib and DEB-TACE in patients with unresectable

HCC is well tolerated and safe, with most toxicities related to sorafenib. This is the only indication for which

sorafenib is listed on the PBS and hence the only Government-subsidised indication for sorafenib in Australia.

Along with renal cell carcinoma, hepatocellular carcinoma is one of the TGA-labelled indications for sorafenib.