Phase 1 study of atrasentan (ABT627), novel endothelin receptor-A antagonist, in Japanes...
`
`Page 1 of 2
`
`This Journal 
`
`Enter search words / phrases / DOI / authors / keywords / etc.
`
`Newest Articles
`
`Issues
`
`Browse By Topic
`
`Special Content
`
`Authors
`
`Subscribers
`
`About
`
`ASCO Journals
`
`Phase 1 study of atrasentan (ABT627), novel
`endothelin receptor-A antagonist, in Japanese
`patients with hormone refractory prostate cancer
`
`Y. Fujisaka, Y. Fujiwara, K. Yamada, T. Shimizu, A. Horiike, N. Yamamoto, Y. Yamada, N.
`Matsuoka...
`
`OPTIONS & TOOLS
`
`Export Citation
`
`Track Citation
`
`Add To Favorites
`
`Rights & Permissions
`
`Show More
`
`Abstract
`
`14602
`
`Background: Endothelin (ET)-1 and its primary receptor, the ETA receptor, contribute
`
`to tumor cell growth, survival, angiogenesis and invasion. Atrasentan is a highly potent,
`
`selective ETA receptor antagonist. This study assessed safety and pharmacokinetics (PK)
`
`in Japanese patients with hormone refractory prostate cancer. Methods: This open-
`
`label, single-center Phase I trial evaluated the safety and PK of escalating oral
`
`atrasentan doses (2.5, 10 or 20 mg) given daily on day 1 and day 4 through 27 (except
`
`day 2 and 3). Dose-limiting toxicity (DLT) was defined as Grade 3 or greater adverse
`
`events related to study drug. Results: Eighteen patients, aged 54–74 (median; 66)
`
`were treated in cohorts of 6 patients each. The compliance of all patients was 100%. The
`
`most common toxicities were rhinitis, peripheral edema, headache, hypotension and
`
`anemia, all of which were well tolerated. These events were consistent with the
`
`anticipated vasodilatory effects or with a hemodilution effect of the study drug. DLTs
`
`were not observed. Atrasentan was rapidly absorbed following oral administration of 2.5
`
`to 20 mg, maximum plasma concentrations averaged from 0.4 to 0.8 hours. After
`
`peaking, plasma concentrations declined bi-exponentially with a terminal half-life of
`
`approximately 25 hours. In the 10 mg dosing group, the steady-state maximum plasma
`
`concentration (Cmax) and the area under the curve (AUC0–24h) averaged 135.5 ng/mL
`
`and 533 ng h/mL, respectively. The Cmax and AUC values generally increased linearly
`
`with increasing dose after single- and multiple-dose administration. Compared to
`
`baseline, PSA decreased 50% or more in 1 patient (20 mg) and increased 25% or more
`
`in 10 patients (2.5 mg;2, 10 mg;5, 20 mg;3). The PSA of the remaining 7 patients (2.5
`
`mg;4, 10 mg;1, 20 mg;2) ranged from < 25% increase to < 50% decrease. Fourteen
`
`patients continued on study drug in an extension study. Conclusions: Atrasentan is
`
`well tolerated, with no dose-limiting adverse events observed up to 20 mg in Japanese
`
`patients. The main adverse events are consistent with the vasodilatory effect of the drug.
`
`PK are linear and dose-proportional; the half-life is appropriate for once-daily dosing.
`
`No significant financial relationships to disclose.
`
`COMPANION ARTICLES
`
`No companion articles
`
`ARTICLE CITATION
`
`DOI: 10.1200/jco.2006.24.90180.14602
`Journal of Clinical Oncology 24, no. 90180
`(June 2006) 14602-14602.
`
`RELATED ARTICLES
`
`Atrasentan, an Endothelin-Receptor
`Antagonist for Refractory Adenocarcinomas:
`Safety and Pharmacokinetics
`Michael A. Carducci et al., J Clin Oncol , 2002
`
`Phase I/II study of docetaxel and atrasentan in
`men with metastatic hormone-refractory
`prostate cancer (HRPC)
`C. N. Moore, J Clin Oncol , 2016
`
`A phase I/II study of docetaxel and atrasentan
`in men with metastatic hormone-refractory
`prostate cancer (HRPC)
`D. J. George, J Clin Oncol , 2016
`
`Effect of Endothelin-A Receptor Blockade With
`Atrasentan on Tumor Progression in Men With
`Hormone-Refractory Prostate Cancer: A
`Randomized, Phase II, Placebo-Controlled Trial
`Michael A. Carducci et al., J Clin Oncol , 2003
`
`Emerging Therapies for Prostate Cancer
`Medscape , 2004
`
`MEDLINE Abstracts: Therapeutic Drug
`Monitoring in HIV Infection
`Medscape , 2002
`
`January 2005
`Jane S. Ricciuti, RPh, MS, Medscape , 2005
`
`Clinical Experience With the HER1/EGFR
`Tyrosine Kinase Inhibitor Erlotinib
`Alan Sandler, MD, Cancer Network , 2003
`
`Powered by
`
`http://ascopubs.org/doi/abs/10.1200/jco.2006.24.90180.14602
`
`12/21/2016
`AVNTIS EXHIBIT 2191 Mylan v.
`Aventis IPR2016-00712
`
`AVENTIS EXHIBIT 2191
`Mylan v. Aventis IPR2016-00712
`
`

`
`Phase 1 study of atrasentan (ABT627), novel endothelin receptor-A antagonist, in Japanes...
`
`Page 2 of 2
`
`WHAT'S POPULAR
`
`Most Read Most Cited
`
`Integration of Palliative Care Into
`Standard Oncology Care: American
`Society of Clinical Oncology Clinical
`Practice Guideline Update
`Ferrell et al.
`
`Squamous Cell Carcinoma of the Breast
`Hennessy et al.
`
`Recommendations for Initial Evaluation,
`Staging, and Response Assessment of
`Hodgkin and Non-Hodgkin Lymphoma:
`The Lugano Classification
`Cheson et al.
`
`HER2 Testing and Clinical Decision
`Making in Gastroesophageal
`Adenocarcinoma: Guideline From the
`College of American Pathologists,
`American Society for Clinical Pathology,
`and the American Society of Clinical
`Oncology
`Bartley et al.
`
`Gleason Score 6 Adenocarcinoma: Should
`It Be Labeled As Cancer?
`Carter et al.
`
`American Society of Clinical Oncology
`2318 Mill Road, Suite 800, Alexandria, VA 22314
`Journal of Clinical Oncology® is a trademark of the American Society of Clinical Oncology
`
`Contact us
`
`http://ascopubs.org/doi/abs/10.1200/jco.2006.24.90180.14602
`
`12/21/2016