BoneKEy Reports | BoneKEy Watch
Atrasentan of no benefit to men with metastatic prostate cancer
DOI:10.1038/bonekey.2013.237
It is known that endothelin-1 produced by tumor cells binds to its receptor at the osteoblast cell surface, stimulating the development of osteoblastic lesions, which are frequently seen in patients with metastatic prostate cancer. This phase III randomized trial investigated whether atrasentan (an endothelin receptor antagonist) in combination with docetaxel was more effective than docetaxel alone in extending the survival of men with metastatic, castration-resistant prostate cancer.
A total of 994 men were split into two groups (n=498, n=496) and treated with docetaxel, 75 mg/m2 i.v. every 21 days, or the same dose of docetaxel plus 10 mg atrasentan given orally each day. Treatment continued for 12 cycles or until toxicity became unacceptable or the disease progressed. Patients with no disease progression at the end of 12 cycles were split into two groups and given 52 weeks of treatment with atrasentan or placebo.
Median progression-free survival was 9.2 months in patients given docetaxel plus atrasentan, and 9.1 months in the docetaxel-only group. Median overall survival was 17.8 months and 17.6 months, respectively. The proportions of patients experiencing grade 3 toxicity or greater were similar in the two groups (57% vs 60%).
Editor’s comment: These results are disappointing, but they do agree with those from a previous phase III clinical trial in men with metastatic castration-resistant prostate cancer. Clearly, the present study sounds the death knell for the use of atrasentan in prostate cancer.
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