Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer.
OBJECTIVE
Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period.


METHODS
In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes.


RESULTS
The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI -1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups.


CONCLUSIONS
Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles.
Smith
Matthew R
MR
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. smith.matthew@mgh.harvard.edu
Morton
Ronald A
RA
Barnette
K Gary
KG
Sieber
Paul R
PR
Malkowicz
S Bruce
SB
Rodriguez
Domingo
D
Hancock
Michael L
ML
Steiner
Mitchell S
MS
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D050723:Fractures, Bone / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012307:Risk Factors; D017312:Toremifene / Q000627:therapeutic use*
D000726:Androgen Antagonists; D050071:Bone Density Conservation Agents; D017312:Toremifene