Atrasentan - A novel selective endothelin-A receptor antagonist

Accumulating data have demonstrated that the endothelin axis plays a role in the progression of many malignancies. Endothelin-1, which is produced by prostate cancer cells, can stimulate new bone formation. It can also act synergistically with a number of growth factors promoting cancer cells growth and proliferation. Over-expression of endothelin-1 and diminished capacity for its clearance have been seen in prostate cancer cell lines. The highest concentration of endothelin-1 is found in patients with hormone refractory metastatic disease. Atrasentan (Xinlay, Abbott) is a member of a new class of drugs called the selective endothelin-A receptor antagonists (SERAs). The safety and efficacy of atrasentan in hormone refractory prostate cancer (HRPC) have been evaluated in several clinical trials. Atrasentan demonstrated some efficacy in delaying the progression of disease and improving patients' quality of life while having an acceptable safety profile. An NDA for atrasentan was submitted in December 2004 for the treatment of patients with HRPC metastatic to bone. A response from FDA is anticipated later this year.