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Updated: Sep 27, 2026
Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model
Published on: November 4, 2022
Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan
Joel B Nelson1, Azmi A Nabulsi, Nicholas J Vogelzang
1Sidney Kimmel Comprehensive Cancer Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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.
Insights
Atrasentan, an endothelin-A receptor antagonist, effectively suppressed bone deposition and resorption markers in hormone refractory prostate cancer patients. This indicates atrasentan
Area of Science:
- Oncology
- Pharmacology
- Bone Metabolism
Background:
- Hormone-refractory prostate cancer (HRPC) often involves bone metastases.
- Bone deposition and resorption markers are indicators of disease progression in bone.
Purpose of the Study:
- To investigate the effects of atrasentan on bone turnover markers and bone scan index in HRPC patients.
- To evaluate atrasentan's efficacy in managing bone complications of prostate cancer.
Main Methods:
- A double-blind, randomized, placebo-controlled trial involving 288 HRPC patients across 74 centers.
- Patients received oral atrasentan (2.5 mg or 10 mg) or placebo daily until disease progression.
- Primary outcome measures included changes in bone deposition (total and bone alkaline phosphatase) and resorption markers (N-telopeptides, C-telopeptides, deoxypyridinoline), and bone scan index.
Main Results:
- Atrasentan (10 mg) significantly stabilized bone alkaline phosphatase levels compared to placebo, which showed marked elevations.
- Patients on 10 mg atrasentan exhibited consistently lower elevations in bone resorption markers (N-telopeptides, C-telopeptides, deoxypyridinoline) versus placebo.
- Bone scan index changes mirrored the biochemical marker trends, suggesting clinical activity.
Conclusions:
- Atrasentan suppressed biochemical markers of bone disease progression in HRPC.
- The study demonstrates atrasentan's clinical activity in hormone-refractory prostate cancer with bone involvement.
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