Denosumab in men receiving androgen-deprivation therapy for prostate cancer.
Details
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_CBA3A7DE7FAD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Denosumab in men receiving androgen-deprivation therapy for prostate cancer.
Journal
The New England journal of medicine
Working group(s)
Denosumab HALT Prostate Cancer Study Group
Contributor(s)
Agus D., Aronoff D., Axler M., Baker K., Brosman S., Chang S., Charu V., Chodak G., Chu F., Cochran J., Colombo G., Dhillon G., Dineen M., Dula E., Efros M., Ekbal S., Feldman R.G., Fisher H., Friedel W., Gittelman M., Gleason D., Goldberg K., Goldfischer E., Gopalakrishnan G., Greengold R., Grossfeld G., Hahn N., Hale B., Hassman D., Hopkins S., Iranmanesh A., Israeli R., Jepson B., Jones W., Kagan R., Karlin G., Katz J., Kaufman J., Keiller D., Kim D., Klimberg I., Kramolowsky E., Lanctin H., Lilly J., Lugg J., Lumerman J., Madorsky M., McMurray J., Mehlhaff B., Mellinger B., Modiano M., Moseley W., Murdock M., Penson D., Reed D., Roberts B., Saltzstein D., Sharkey J., Shepherd D., Sidhom A., Sieber P., Sipio J., Smith R., Smith F., Steidle C., Tchekmedyian S., Teigland C., Thrasher J., Tomera K., Updegrove J., Wachs B., Wells W.G., Whitlock N., Williams R., Wurzel R., Yee L., Aaron L., Andreou C., Barkin J., Bora B., Buckley R., Casey R., Chetner M., Chin J., DiConstanzo G., Donnelly B., Flax S., Gleave M., Goldfarb B., Hewitt R., Hirshberg E., Jansz K., Kapoor A., Kinahan T., Klotz L., Lacombe L., Leung W., Liquornik M., Love W., Mathur A., Morash C., Okafo B., Palmer B., Pommerville P., Siemens D.R., Steinhoff G., Tanguay S., Trachtenberg J., Woods E., Zadra J., Cruz-Rodriguez M., Galicia-Samano R., Hernandez-Ordonez O., Martinez-Martinez C., Robles-Avina J., Octavio-Rovelo-Diaz C., Suarez-Sahui T., Vargas-Zamora H., Bar K., Darewicz B., Demkow T., Jablonska Z., Jarzemski P., Kania P., Niezabitowski J., Pypno W., Szwedowski R., Hanus M., Hesoun P., Jansa J., Pacik D., Pernicka J., Richter J., Urban M., Zmeskal P., Barten E., van den Broeke P.J., Bruins J.L., Khoe G., Kil P.J., Meier A.H., van Berkel J., Body G., Kondas J., Koranyi L., Tenke P., Torzsok F., Toth T., Lamy O., Lippuner K., Theiler R., Leppilahti M.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Publication state
Published
Issued date
20/08/2009
Volume
361
Number
8
Pages
745-755
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer.
In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures.
At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups.
Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)
In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures.
At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups.
Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)
Keywords
Aged, Aged, 80 and over, Androgen Antagonists/adverse effects, Androgen Antagonists/therapeutic use, Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal/pharmacology, Antibodies, Monoclonal/therapeutic use, Antibodies, Monoclonal, Humanized, Bone Density/drug effects, Bone Density Conservation Agents/adverse effects, Bone Density Conservation Agents/pharmacology, Bone Density Conservation Agents/therapeutic use, Bone Remodeling/drug effects, Denosumab, Double-Blind Method, Fractures, Bone/epidemiology, Fractures, Bone/prevention & control, Gonadotropin-Releasing Hormone/agonists, Humans, Incidence, Injections, Subcutaneous, Lumbar Vertebrae/drug effects, Lumbar Vertebrae/injuries, Lumbar Vertebrae/physiology, Male, Middle Aged, Orchiectomy, Osteoporosis/chemically induced, Osteoporosis/drug therapy, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/physiopathology, Prostatic Neoplasms/surgery, RANK Ligand/adverse effects, RANK Ligand/pharmacology, RANK Ligand/therapeutic use, Spinal Fractures/epidemiology, Spinal Fractures/prevention & control
Pubmed
Open Access
Yes
Create date
04/02/2017 16:07
Last modification date
20/08/2019 15:46
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