Sorafenib is also known as Nexevar. Sorafenib has shown promising results as a second-line treatment for metastatic kidney cancer in patients in whom prior interferon or interleukin therapy had failed. Sorafenib was initially designed to block a specific signalling pathway (Ras/Raf) which causes cells to grow and develop their own blood vessels. Sorafenib was later discovered to block multiple different cell pathways and growth factors (VEGFR1, VEGFR2, VEGFR3, FMS-like tyrosine kinase 3, Platelet-derived Growth Factor receptor b). When given as a treatment for metastatic kidney cancer, Sorafenib is recommended to be given on an empty stomach at a dose of 400 mg orally twice daily.
In 2006 the results of a phase II study tested Sorafenib in patients with advanced kidney cancer demonstrated that after 12 weeks, 4% of patients had a partial response; however, 36% of patients had some degree of kidney cancer shrinkage and 34% of patients showed stabilized disease without progression. In the second part of this trial, patients were randomized to either continue their present Sorafenib dosage or switch to placebo (sugar pill to test to see if the medicine is really effective). Patients were then monitored over the next 12 weeks for disease progression. At the end of 12 weeks, 50% of patients who had continued on Sorafenib were progression free, compared with 18% of patients randomized to placebo. The average time for progression of the kidney cancer in patients taking Sorafenib was 24 weeks, compared to only 6 weeks in the patients taking the placebo.
The largest clinical trial involving patients with metastatic kidney cancer and Sorafenib was a study published in the New England Journal of Medicine in 2007. Information on patients from multiple different centers was collected. 903 patients with metastatic kidney cancer were given either Sorafenib or a placebo. Overall, Sorafenib was shown to be more efficacious than placebo. Sorafenib stabilized the disease in 74% of the patients. Progression-free survival (patients whose disease did not get worse) was also significantly in favor of the Sorafenib group (5.5 months versus 2.8 months). The overall survival was also longer in the group of patients who were taking Sorafenib (19.3 months for Sorafenib and 15.9 months for placebo).
Sorafenib has also been tested as a primary treatment (for patients who had not received any treatment for the kidney cancer prior to starting the medicine) strategy in patients with metastatic kidney cancer. In 2007, Sorafenib was compared to interferon treatment in patients with metastatic kidney cancer. In this study, there was no benefit (over interferon) to taking Sorafenib regarding either progression-free survival or response rate. Also in 2007 another study evaluated the combination of Sorafenib and IFN-a as first-line therapy for patients with metastatic kidney cancer. Although this combination showed a relatively good response rate (about 20%) with a median progression-free survival of 7 months (which is very favourable compared with other frontline therapies), this schedule was marked by a 77% incidence of complications which were challenging to the patients taking the medications.
Overall, with the limited information that is currently available, the recommendation for Sorafenib is that this medication be used as second-line treatment for metastatic kidney cancer after other treatments have failed.
|
