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A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer

Carducci, Michael A.; Saad, Fred; Abrahamsson, Per-Anders LU ; Dearnaley, David R.; Schulman, Claude C.; North, Scott A.; Sleep, Darryl J.; Isaacson, Jeffrey D. and Nelson, Joel B. (2007) In Cancer 110(9). p.1959-1966
Abstract
BACKGROUND. The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone- refractory prostate cancer (HRPC). METHODS. This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. RESULTS. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence... (More)
BACKGROUND. The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone- refractory prostate cancer (HRPC). METHODS. This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. RESULTS. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P =.136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P <.05 for each). The median time to BAP progression (> 50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P <.01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. CONCLUSIONS. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
time to disease progression, prostate cancer, hormone-refractory, atrasentan, endothelin-A receptor antagonist, bone metastasis
in
Cancer
volume
110
issue
9
pages
1959 - 1966
publisher
John Wiley & Sons
external identifiers
  • wos:000250422500010
  • scopus:35648968713
ISSN
1097-0142
DOI
10.1002/cncr.22996
language
English
LU publication?
yes
id
4193784d-f6f0-485c-bbb9-08311c04530d (old id 653206)
date added to LUP
2007-12-11 16:43:36
date last changed
2017-10-08 03:28:50
@article{4193784d-f6f0-485c-bbb9-08311c04530d,
  abstract     = {BACKGROUND. The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone- refractory prostate cancer (HRPC). METHODS. This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. RESULTS. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P =.136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P &lt;.05 for each). The median time to BAP progression (&gt; 50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P &lt;.01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. CONCLUSIONS. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.},
  author       = {Carducci, Michael A. and Saad, Fred and Abrahamsson, Per-Anders and Dearnaley, David R. and Schulman, Claude C. and North, Scott A. and Sleep, Darryl J. and Isaacson, Jeffrey D. and Nelson, Joel B.},
  issn         = {1097-0142},
  keyword      = {time to disease progression,prostate cancer,hormone-refractory,atrasentan,endothelin-A receptor antagonist,bone metastasis},
  language     = {eng},
  number       = {9},
  pages        = {1959--1966},
  publisher    = {John Wiley & Sons},
  series       = {Cancer},
  title        = {A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer},
  url          = {http://dx.doi.org/10.1002/cncr.22996},
  volume       = {110},
  year         = {2007},
}