Toremifene improves lipid profiles in men receiving androgen-deprivation therapy for prostate cancer: interim analysis of a multicenter phase III study.
OBJECTIVE
Androgen-deprivation therapy (ADT) is associated with greater risk of incident coronary heart disease and hospital admission for myocardial infarction; treatment-related increases in serum lipids may contribute to greater cardiovascular disease risk. We evaluated the effects of toremifene, a selective estrogen-receptor modulator, on fasting serum lipid levels in men receiving ADT for prostate cancer.


METHODS
In an ongoing, multicenter, double-blind, placebo-controlled phase III fracture-prevention study, 1,389 men receiving ADT for prostate cancer were randomly assigned to receive toremifene (80 mg/d) or placebo. In this interim analysis of 188 patients, changes in fasting serum lipids from baseline to month 12 were compared between the placebo and toremifene groups.


RESULTS
Changes in serum lipids differed significantly between the groups. Mean (+/- SE) total cholesterol decreased by 1.0% +/- 1.7% from baseline to month 12 in the placebo group and decreased by 8.1% +/- 1.4% in the toremifene group (P = .001 for between group comparison). Low-density lipoprotein (LDL) cholesterol increased by 0.8% +/- 2.5% in the placebo group and decreased by 8.2% +/- 2.5% in the toremifene group (P = .003). In contrast, high-density lipoprotein (HDL) cholesterol decreased by 4.9% +/- 1.2% in the placebo group and increased by 0.5% +/- 2.2% in the toremifene group (P = .018). Triglycerides increased by 6.9% +/- 4.2% in the placebo group and decreased by 13.2% +/- 3.6% in the toremifene group (P = .003).


CONCLUSIONS
Toremifene significantly decreased total cholesterol, LDL cholesterol, and triglycerides, and increased HDL cholesterol in men receiving ADT for prostate cancer.
Smith
Matthew R
MR
Massachusetts General Hospital Cancer Center, Yawkey 7038, 55 Fruit St, Boston, MA 02114, USA. smith.matthew@mgh.harvard.edu
Malkowicz
S Bruce
SB
Chu
Franklin
F
Forrest
John
J
Sieber
Paul
P
Barnette
K Gary
KG
Rodriquez
Domingo
D
Steiner
Mitchell S
MS
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D017759:Fractures, Malunited / Q000517:prevention & control; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017312:Toremifene / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D017312:Toremifene; D002784:Cholesterol