Suppression of Prostate Cancer Induced Bone Remodeling by The Endothelin Receptor a Antagonist Atrasentan
2003; Lippincott Williams & Wilkins; Volume: 169; Issue: 3 Linguagem: Inglês
10.1097/01.ju.0000042162.08938.27
ISSN1527-3792
AutoresJoel B. Nelson, Azmi Nabulsi, Nicholas J. Vogelzang, Jürgen Breul, Bernard A. Zonnenberg, Danai Daliani, Claude C. Schulman, Michael A. Carducci,
Tópico(s)Thyroid Disorders and Treatments
ResumoNo AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Mar 2003Suppression of Prostate Cancer Induced Bone Remodeling by The Endothelin Receptor a Antagonist Atrasentan JOEL B. NELSON, AZMI A. NABULSI, NICHOLAS J. VOGELZANG, JURGEN BREUL, BERNARD A. ZONNENBERG, DANAI D. DALIANI, CLAUDE C. SCHULMAN, and MICHAEL A. CARDUCCI JOEL B. NELSONJOEL B. NELSON , AZMI A. NABULSIAZMI A. NABULSI , NICHOLAS J. VOGELZANGNICHOLAS J. VOGELZANG , JURGEN BREULJURGEN BREUL , BERNARD A. ZONNENBERGBERNARD A. ZONNENBERG , DANAI D. DALIANIDANAI D. DALIANI , CLAUDE C. SCHULMANCLAUDE C. SCHULMAN , and MICHAEL A. CARDUCCIMICHAEL A. CARDUCCI View All Author Informationhttps://doi.org/10.1097/01.ju.0000042162.08938.27AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We examined the effects of atrasentan (endothelin-A receptor antagonist) on bone deposition and resorption markers and on bone scan index. Materials and Methods: This double-blind, randomized, placebo controlled clinical trial of hormone refractory prostate cancer patients was done at 74 medical centers in the United States and Europe. A total of 288 asymptomatic patients with hormone refractory prostate adenocarcinoma and evidence of metastatic disease were randomized to 1 of 3 treatment groups, namely 2.5 mg. atrasentan, 10 mg. atrasentan or placebo administered orally daily until disease progression. The main outcomes measures were changes in bone deposition markers (total alkaline phosphatase and bone alkaline phosphatase) and bone resorption (N-telopeptides, C-telopeptides and deoxypyridinoline), and in the bone scan index. Results: At baseline markers of bone deposition and resorption were elevated 1.4 to 2.7-fold above respective upper limits of normal. Subjects receiving placebo experienced a 58% elevation in mean total alkaline phosphatase and a 99% elevation in mean bone alkaline phosphatase (p <0.001), whereas subjects receiving 10 mg. atrasentan maintained stable mean total alkaline phosphatase and bone alkaline phosphatase values compared with baseline. N-telopeptides, C-telopeptides and deoxypyridinoline elevation from baseline were consistently less in patients receiving 10 mg. atrasentan compared with placebo. Similar trends were observed in subjects who received 2.5 mg. atrasentan. Changes in clinical bone scan studies paralleled bone marker changes. Conclusions: Atrasentan suppressed markers of biochemical and clinical prostate cancer progression in bone and demonstrates clinical activity for hormone refractory prostate cancer. References 1 Globocan 2000: Cancer Incidence, Mortality and Prevalence Worldwide. 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Google Scholar From the Sidney Kimmel Comprehensive Cancer Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland; Abbott Laboratories, Abbott Park and Section of Hematology/Oncology, Department of Medicine and Cancer Research Center, University of Chicago, Chicago, Illinois; Urologische Klinik und Poliklinik, Klinikum rechts der Isar, Munchen, Germany; Department of Medical Oncology, University Medical Centre, Utrecht, The Netherlands; Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas; Department of Urology, University Hospital Erasme, Brussels, Belgium; and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byTaneja S (2018) Re: Docetaxel and Atrasentan versus Docetaxel and Placebo for Men with Advanced Castration-Resistant Prostate Cancer (SWOG S0421): A Randomised Phase 3 TrialJournal of Urology, VOL. 191, NO. 3, (656-658), Online publication date: 1-Mar-2014. Volume 169Issue 3March 2003Page: 1143-1149 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsprostatebone and bonesneoplasm metastasisprostatic neoplasmsreceptors, endothelinMetricsAuthor Information JOEL B. NELSON Requests for reprints: University of Pittsburgh School of Medicine, 5200 Center Ave., Pittsburgh, PA 15232. Financial interest and/or other relationship with Abbott Laboratories. More articles by this author AZMI A. NABULSI Financial interest and/or other relationship with Abbott Laboratories. More articles by this author NICHOLAS J. VOGELZANG Financial interest and/or other relationship with Abbott Laboratories, Yamanouchi, TAP, Astra Zeneca, National Cancer Institute, American Cancer Society and Eli Lilly. More articles by this author JURGEN BREUL Financial interest and/or other relationship with Abbott Laboratories. More articles by this author BERNARD A. ZONNENBERG Financial interest and/or other relationship with Abbott Laboratories, Astra Zeneca and Mallinckrodt. More articles by this author DANAI D. DALIANI Financial interest and/or other relationship with Abbott Laboratories, Astra Zeneca and Mallinckrodt. More articles by this author CLAUDE C. SCHULMAN Financial interest and/or other relationship with Celgene, Abbott Laboratories and Aventis. More articles by this author MICHAEL A. CARDUCCI Financial interest and/or other relationship with Abbott Laboratories, Aventis Oncology and Eli Lilly. More articles by this author Expand All Advertisement PDF downloadLoading ...
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