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Article first published online: 10 SEP 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 9, pages 2478–2487, 1 November 2008
How to Cite
Nelson, J. B., Love, W., Chin, J. L., Saad, F., Schulman, C. C., Sleep, D. J., Qian, J., Steinberg, J., Carducci, M. and for the Atrasentan Phase 3 Study Group (2008), Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer, 113: 2478–2487. doi: 10.1002/cncr.23864
See editorial on pages 2376–8, this issue.
Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, June 1-5, 2007.
- Issue published online: 17 OCT 2008
- Article first published online: 10 SEP 2008
- Manuscript Accepted: 5 MAY 2008
- Manuscript Revised: 5 MAR 2008
- Manuscript Received: 8 JAN 2008
- Abbott Laboratories, Abbott Park, Illinois
- bone alkaline phosphatase;
- hormone-refractory prostate cancer;
- objective metastatic disease;
- prostate-specific antigen doubling time
Atrasentan is a potent, oral, selective endothelin-A (ETA) receptor antagonist that has clinical activity in patients with hormone-refractory prostate cancer (HRPC). In this article, the authors report the results from a phase 3, randomized, double-blind, placebo-controlled trial of atrasentan in patients with nonmetastatic HRPC.
Of 941 patients who had adequate androgen suppression and no radiographic evidence of metastases but rising prostate-specific antigen (PSA) levels, 467 patients were randomized to receive atrasentan at a dose of 10 mg, and 474 patients were randomized to receive placebo daily. The primary endpoint was the time to disease progression (TTP), which was defined as the onset of metastases. Secondary endpoints were the time to PSA progression, change in bone alkaline phosphatase (BALP) levels, PSA doubling time, and overall survival.
There was a 93-day delay in the median TTP with atrasentan, but the difference from placebo in TTP was not statistically significant (P = .288). Large geographic differences in the median TTP were noted: in the US: The difference was 81 days longer with placebo; whereas, in non-US sites, the difference was 180 days longer with atrasentan. Atrasentan lengthened the PSA doubling time (P = .031) and slowed the increase in BALP (P < .001). The median survival was 1477 days with atrasentan and 1403 days with placebo. The most common adverse events associated with atrasentan were peripheral edema, nasal congestion, and headache, consistent with the vasodilatory properties of ETA receptor antagonists.
Although the primary endpoint was not achieved, large regional differences in TTP were noted, suggesting that trial conduct may have influenced the results. The biologic activity was consistent with findings from other clinical trials of atrasentan in HRPC. Cancer 2008. © 2008 American Cancer Society.