Anticancer agent - BAY 43-9006
Many different strategies are being investigated as potential cancer treatments. One such molecule is BAY 43-9006, being co-developed by Bayer and Onyx Pharmaceuticals.1
Many different strategies are being investigated as potential cancer treatments. One such molecule is BAY 43-9006, being co-developed by Bayer and Onyx Pharmaceuticals.1
This potential drug is a signal transduction inhibitor that combines two different anticancer activities: it targets tumour cell proliferation and angiogenesis. For the former, it inhibits the enzyme RAF kinase, a critical component in the RAS pathway, a cascade of chemical signals that controls cell division. And for the latter, it inhibits both VEGFR-2 and PDGFR-b, which are key receptors for vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF), both of which play important roles in angiogenesis. Phase I studies showed it had potential in a variety of solid tumours.
BAY 43-9006 is being investigated as a potential treatment for renal cell carcinoma. In a Phase II multi-centre randomised discontinuation trial, more than 200 patients with renal cell carcinoma first went through a 12 week induction phase, followed by a randomisation phase and a parallel BAY 43-9006 open label phase.2 During the first phase, all participants received the active twice a day in oral doses of 400mg. Those patients whose tumour burden was within 25% of their pre-treatment measurements were randomised to the active or placebo for a further 12 weeks; 13 of these had tumour shrinkage of over 50%. A total of 37 had shrinkage in excess of 25% after the first 12 weeks, and these continued treatment with open label BAY 43-9006. Those whose tumours grew by more than 25% were discontinued from the study.
The drug is also being investigated as a potential treatment for melanoma. In a Phase I/II study, 30 patients were given a combination of BAY 43-9006, carboplatin and paclitaxel.3 Forty percent saw their tumour shrink by at least 50%, and a further 43% experienced disease stabilisation. All of these effects lasted for six months or more. After 10-12 months, only three of these subjects had succumbed to disease progression.
A Phase III trial is now under way in renal cell carcinoma patients, and it is also being investigated as a treatment for a variety of other cancers, including solid tumours.