par Schulman, Claude 
Référence European urology. Supplement, 2, 3, page (20-27)
Publication Publié, 2003-03
Référence European urology. Supplement, 2, 3, page (20-27)
Publication Publié, 2003-03
Article révisé par les pairs
| Résumé : | Dysregulation of the endothelin axis has been implicated in the progression of prostate cancer; thus providing a potential therapeutic target. Atrasentan is a potent, selective, endothelin-A (ETA) receptor antagonist that has been shown to block the mitogenic, anti-apoptotic, and bone-remodelling activity of endothelin-1 (ET-1) in pre-clinical studies. Orally bioavailable, with a half-life suitable for once-daily dosing, atrasentan will provide optimal convenience for patients requiring long-term therapy. Phase I dose-escalation studies have shown the drug to be well tolerated at a clinical dose of 10 mg in patients with hormone-refractory prostate cancer (HRPC). This favourable tolerability profile has been confirmed in phase II studies, in which headache, rhinitis, asthenia and peripheral oedema have been identified as the most common adverse events. Recently, a large, multi-centre, phase II study has indicated that atrasentan delayed disease progression and time to prostate serum antigen (PSA) progression in metastatic HRPC, and was associated with improvements in quality of life compared with placebo. Furthermore, evidence has emerged from this and other studies that atrasentan may attenuate tumour-induced bone remodelling, impeding the progression of skeletal disease in patients with HRPC. Atrasentan is currently being investigated in two phase III clinical studies, one in patients with advanced metastatic HRPC, the other in patients with non-metastatic HRPC who are failing hormonal ablation therapy. The results are awaited with interest. © 2003 Elsevier Science B.V. All rights reserved. |
