Toremifene - A promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy

Expert Opinion on Investigational Drugs

Volumn 15, Issue 3, 2006, Pages 293-305

  Taneja, Samir S ^a   Smith, Matthew R ^b   Dalton, James T ^c   Raghow, Sharan ^c   Barnette, Gary ^c   Steiner, Mitchell ^c   Veverka, Karen A ^c  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c GTx Inc   (United States)

Author keywords

Androgen deprivation therapy; Androgen receptor; Carcinoma; Estrogen receptor; Gonadotropin releasing hormone; High grade prostate intraepithelial neoplasia; Osteoclast; Osteoporosis; Prostate cancer; Resorption; Selective estrogen receptor modulator; Toremifene

Indexed keywords

ALKALINE PHOSPHATASE BONE ISOENZYME; CALCIUM; CARBOXY TERMINAL TELOPEPTIDE; DOXORUBICIN; DUTASTERIDE; ESTROGEN; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FINASTERIDE; FLUTAMIDE; GONADORELIN AGONIST; HISTONE ACETYLTRANSFERASE PCAF; MITOGEN ACTIVATED PROTEIN KINASE; NUCLEAR RECEPTOR COACTIVATOR 2; OSTEOCALCIN; PLACEBO; RALOXIFENE; RIFAMPICIN; SELECTIVE ESTROGEN RECEPTOR MODULATOR; STEROID RECEPTOR COACTIVATOR 1; TAMOXIFEN; TOREMIFENE; TRANSCRIPTION FACTOR AP 1; VITAMIN D;

ANTINEOPLASTIC ACTIVITY; BONE DENSITY; BONE MINERAL; BONE TURNOVER; BREAST CANCER; CANCER HORMONE THERAPY; CANCER INHIBITION; CANCER PREVENTION; CANCER RISK; CARCINOGENESIS; CLINICAL TRIAL; CONCENTRATION RESPONSE; DISEASE COURSE; DIZZINESS; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG COMPETITION; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG FATALITY; DRUG HALF LIFE; DRUG INDICATION; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; EDEMA; ESTROGEN ACTIVITY; FOOD DRUG INTERACTION; FRACTURE; GYNECOMASTIA; HOT FLUSH; HUMAN; NAUSEA; NONHUMAN; ORCHIECTOMY; OSTEOPOROSIS; PAIN; PATHOPHYSIOLOGY; PROSTATE CANCER; PROTEIN FUNCTION; REVIEW; RISK REDUCTION; SIDE EFFECT; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SWEATING; THROMBOEMBOLISM; VAGINA DISCHARGE; VOMITING;

ANDROGEN ANTAGONISTS; ANDROGENS; ANTINEOPLASTIC AGENTS, HORMONAL; HUMANS; MALE; PROSTATIC NEOPLASMS; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TOREMIFENE;

EID: 33644765995     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.15.3.293     Document Type: Review

References (150)

1. JEMAL A, MURRAY T, WARD E, et al: Cancer statistics, 2005. CA Cancer J. Clin. (2005) 55(1):10-30.
2. BOSTWICK DG, BRAWER MK: Prostatic intra-epithelial neoplasia and early invasion in prostate cancer. Cancer (1987) 59(4):788-794.
3. STEINER MS. High-grade prostatic intraepithelial neoplasia and prostate cancer risk reduction. World J. Urol. (2003) 21(1):15-20.
4. SAKR WA, LUCIA MS: Potential pathologic markers for prostate chemoprevention studies. Urol. Clin. North Am. (2004) 31(2):227-235.
5. SCHLESINGER C, BOSTWICK DG, ICZKOWSKI KA: High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation: predictive value for cancer in current practice. Am. J. Surg. Pathol. (2005) 29(9):1201-1207.
6. ZENG L, KYPRIANOU N: Apoptotic regulators in prostatic intraepithelial neoplasia (PIN): value in prostate cancer detection and prevention. Prostate Cancer Prostatic Dis. (2005) 8(1):7-13.
7. LEFKOWITZ GK, TANEJA SS, BROWN J et al.: Follow up interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels. J. Urol. (2002) 168(4 Part 1):1415-1418.
8. KELLOFF GJ, LIEBERMAN R, BRAWER MK et al.: Strategies for chemoprevention of prostate cancer. Prostate Cancer Prostatic Dis. (1999) 2(S1):27-33.
9. LIEBERMAN R: Chemoprevention of prostate cancer: current status and future directions. Cancer Metastis. Pev. (2002) 21(3-4):297-309.
10. MOYAD MA, CARROLL PR: Lifestyle recommendations to prevent prostate cancer, part II: time to redirect our attention? Urol. Clin. North Am. (2004) 31(2)301-311.
11. STRATTON MS, REID ME, SCHWARTZBERG G et al.: Selenium and prevention of prostate cancer in high-risk men: the Negative Biopsy Study. Anticancer Drugs (2003) 14(8):589-594.
12. ANDRIOLE G, BOSTWICK D, BRAWLEY O et al.: Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial. J. Urol. (2004) 172(4 Part 1):1314-1317.
13. KLEIN EA, THOMPSON IM, LIPPMAN SM et al.: SELECT: the selenium and vitamin E cancer prevention trial. Urol. Oncol. (2003) 21:59-65.
14. GUPTA S: Prostate cancer chemoprevention: models, limitations and potential. Int. J. Oncol. (2004) 25:1133-1148.
15. THOMPSON IM, GOODMAN PJ, TANGEN CM et al.: The influence of finasteride in the development of prostate cancer. N. Engl. J. Med. (2003) 349:215-224.
16. BOSLAND MC: The role of steroid hormones in prostate carcinogenesis. J. Natl. Cancer Inst. Monogr. (2000) 27:39-66.
17. HO SM: Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates. J. Cell Biochem. (2004) 91(3):491-503.
18. SUZUKI K, NAKAZATO H, MATSUI H et al.: Genetic polymorphisms of estrogen receptor α, CYP 19, catechol-O-methyltransferase are associated with familial prostate carcinoma risk in a Japanese population. Cancer (2003) 98(7):1411-1416.
19. SHARIFI N, GULLEY JL, DAHUT WL: Androgen deprivation therapy for prostate cancer. J. Am. Med. Assoc. (2005) 294(2):238-244.
20. LOBLAW DA, MENDELSON DS, TALCOTT JA et al: American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J. Clin. Oncol. (2004) 22(14):2927-2941.
21. SHAHINIAN VB, KUO YF, FREEMAN JL et al.: Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer (2005) 103(8):1615-1624.
22. STOCH SA, PARKER RA, CHEN L et al.: Bone Loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J. Clin. Endocrinol. Metab. (2001) 86(6):2787-2791.
23. KEY T, APPLEBY P, BARNES I et al.: Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J. Natl. Cancer Inst. (2002) 94(8):606-616.
24. BRENNER H: Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet (2002) 360(9340):1131-1135.
25. LINDBERG MK, VANDENPUT L, MOVERARE SS et al: Androgens and the skeleton. Minerva Endocrinol. (2005) 30(1):15-25.
26. ADAMS JY, LEAV I, LAU KM et al.: Expression of estrogen receptor β in the fetal, neonatal, and prepubertal human prostate. Prostate (2002) 52(1):69-81.
27. MULLER M, VAN DER SCHOUW YT, THIJSSEN JH et al: Endogenous sex hormones and cardiovascular disease in men. J. Clin. Endocrinol. Metab. (2003) 88(11):5076-5086.
28. KATZENELLENBOGEN BS, CHOI I, DELAGE-MOURROUX R et al: Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology. J. Steroid Biochem. Mol. Biol. (2000) 74(5):279-285.
29. YI P, DRISCOLL MD, HUANG J et al.: The effects of estrogen-responsive element and ligand-induced structural changes on the recruitment of cofactors and transcriptional responses by ERα and ERβ. Mol. Endocrinol. (2002) 16(4):674-693.
30. BJORNSTROM L, SJOBERG M: Estrogen receptor-dependent activation of AP-1 via non-genomic signaling. Nucl. Recept. (2004) 2(1):3.
31. SMITH CL, O'MALLEY BW: Coregulator function: a key to understanding tissue specificity of selective estrogen receptor modulators. Endocr. Rev. (2004) 25(1):45-71.
32. GLASS CK, ROSENFELD MG: The co-regulator exchange in transcriptional functions of nuclear receptors. Genes Dev. (2000) 14:121-141.
33. JAKACKA M, ITO M, WEISS J: Estrogen receptor binding to DNA is not required for its activity through the nonclassical AP1 pathway. J. Biol. Chem. (2001) 276(17):13615-13621.
34. SAFE S: Transcriptional activation of genes by 17-β-estradiol through estrogen receptor-Sp1 interactions. Vitam. Horm. (2001) 62:231-252.
35. McDONNELL DP, CHANG CY, NORRIS JD: Capitalizing on the complexities of estrogen receptor pharmacology in the quest for the perfect SERM. Ann. NY Acad. Sci. (2001) 949:16-35.
36. MEEGAN MJ, LLOYD DG: Advances in the science of estrogen receptor modulation. Curr. Med. Chem. (2003) 10 (3):181-210.
37. HUBBARD RE, PIKE AC, BRZOZOWSKI AM et al.: Structural insights into the mechanisms of agonism and antagonism in oestrogen receptor isoforms. Eur. J. Cancer (2000) 36(Suppl. 4):S17-S18.
38. MONROE DG, SECRETO FJ, SUBRAMANIAM M et al.: Estrogen receptor α and β heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2OS osteosarcoma cells. Mol. Endocrinol. (2005) 19(6):1555-1568.
39. KIAN TEE M, ROGATSKY I, TZAGARAKIS-FOSTER. C et al: Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors α and β. Mol. Biol. Cell. (2004) 15(3):1262-1272.
40. QIAN YM, SUN XJ, TONG MH et al.: Targeted disruption of the mouse estrogen sulfotransferase gene reveals a role of estrogen metabolism in intracrine and paracrine estrogen regulation. Endocrinology (2001) 142(12):5342-5350.
41. PLATZ EA, GIOVANNUCCI E: The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer. J. Steroid Biocbem. Mol. Biol. (2004) 92(4):237-253.
42. RISBRIDGER GP, BIANCO JJ, ELLEM SJ, McPHERSON SJ: Oestrogens and prostate cancer. Endocr. Relat. Cancer (2003) 10(2):187-91.
43. SORONEN P, LAITI M, TORN S et al: Sex steroid hormone metabolism and prostate cancer. J. Steroid Biochem. Mol. Biol. (2004) 92(4):281-286.
44. PRINS GS, BIRCH L, COUSE JF et al.: Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor α: studies with αERKO and βERKO mice. Cancer Res. (2001) 61(16):6089-6097.
45. LATIL AG, AZZOUZI R, CANCEL GS et al.: Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer (2001) 92(5):1130-1137.
46. ZHU X, LEAV I, LEUNG YK et al.: Dynamic regulation of estrogen receptor-β expression by DNA methylation during prostate cancer development and metastasis. Am. J. Pathol. (2004) 164 (6):2003-2012.
47. DEMARZO AM, NELSON WG, ISAACS WB, EPSTEIN JI: Pathological and molecular aspects of prostate cancer. Lancet (2003) 361(9361):955-964.
48. MAKELA S, STRAUSS L, KUIPER G et al.: Differential expression of estrogen receptors α and β in adult rat accessory sex glands and lower urinary tract. Mol. Cell Endocrinol. (2000) 170(1-2):219-229.
49. LEAV I, LAU KM, ADAMS JY et al.: Comparative studies of the estrogen receptors β and α and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am. J. Pathol. (2001) 159(1):79-92.
50. FIXEMER T, REMBERGER K, BONKHOFF H: Differential expression of the estrogen receptor β (ERβ) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma. Prostate (2003) 54(2):79-87.
51. SKLIRIS GP, MUNOT K, BELL SM et al.: Reduced expression of oestrogen receptor β in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model. J. Pathol. (2003) 201(2):213-220.
52. JI Q, LIU PI, ELSHIMALI Y, STOLZ A: Frequent loss of estrogen and progesterone receptors in human prostatic tumors determined by quantitative real-time PCR. Mol. Cell Endocrinol. (2005) 229(1-2):103-110.
53. LAU KM, LASPINA M, LONG J et al.: Expression of estrogen receptor (ER)-α and ER-β in normal and malignant prostatic epithelial cells: regulation by methylation and involvement in growth retardation. Cancer Res, (2000) 60(12):3175-3182.
54. GUERINI V, SAU D, SCACCIANOCE E et al.: The androgen derivative 5α-androstane-3β,17β-diol inhibits prostate cancer cell migration through activation of the estrogen receptor β subtype. Cancer Res. (2005) 65(12):5445-5453.
55. SIGNORETTI S, LODA M: Estrogen receptor β in prostate cancer: brake pedal or accelerator? Am. J. Pathol. (2001) 159(1):13-16.
56. CHENG J, LEE EJ, MADISON LD, LAZENNEC G: Expression of estrogen receptor β in prostate carcinoma cells inhibits invasion and proliferation and triggers apoptosis. FEBS Lett. (2004) 566(1-3):169-172.
57. IMAMOV O, MORANI A, SHIM GJ et al.: Estrogen receptor β regulates epithelial cellular differentiation in the mouse ventral prostate. Proc. Natl. Acad. Sci. USA (2004) 101(25):9375-9380.
58. BARDIN A, BOULLE N, LAZENNEC G et al.: Loss of ERβ expression as a common step in estrogen-dependent tumor progression. Endocr. Relat. Cancer (2004) 11(3):537-551.
59. RISBRIDGER G, WANG H, YOUNG P et al.: Evidence that epithelial and mesenchymal estrogen receptor-α mediates effects of estrogen on prostatic epithelium. Dev. Biol. (2001) 231(1):289.
60. COUSE JF, KORACH KS: Estrogen receptor-α mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the routine reproductive tract. Toxicology (2004) 205(1-2):55-63.
61. BRZOZOWSKI AM, PIKE AC, DAUTER Z et al.: Molecular basis of agonism and antagonism in the oestrogen receptor. Nature (1997) 389(6652)753-758.
62. SHIAU AK, BARSTAD D, LORIA PM et al.: The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell (1998) 95(7):927-937.
63. KATO S, ENDOH H, MASUHIRO Y et al.: Activation of the estrogen receptor through phosphorylation by mitogen activated protein kinase. Science (1995) 270(5241):1491-1494.
64. BUNONE G, BRIAND PA, MIKSICEK RJ et al.: Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J. (1996) 15(9):2174-2183.
65. KONG EH, HELDRING N, GUSTAFSSON JA et al.: Delineation of a unique protein-protein interaction site on the surface of the estrogen receptor. Proc. Natl. Acad. Sci. USA (2005) 102(10)3593-3598.
66. LIU H, LEE E-S, DE LOS REYES A et al.: Silencing and reactivation of the selective estrogen receptor modulator a complex. Cancer Res. (2001) 61:3632-3639.
67. WOOD JR, GREENE GL, NARDULLI AM: Estrogen response elements function as allosteric modulators of estrogen receptor conformation. Mol. Cell Biol. (1998) 18(4):1927-1934.
68. KLINGE CM, JERNIGAN SC, MATTINGLY KA: Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors. J. Mol. Endocrinol. (2004) 33(2):387-410.
69. ERIKSEN ER, COLVARD DS, BERG NJ et al.: Evidence of estrogen receptors in normal human osteoblast-like cells. Science (1988) 241(4861):84-86.
70. COLVARD DS, ERIKSEN EF, KEETING PE et al.: Identification of androgen receptors in normal human osteoblast-like cells. Proc. Natl. Acad. Sci. USA (1989) 86(3):854-857.
71. OURSLER MJ, LANDERS JP, RIGGS BL et al.: Oestrogen effects on osteoblasts and osteoclasts. Ann. Med. (1993) 25(4):361-371.
72. MIZUNO Y, HOSOI T, INOUE S et al.: Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells. Calcif. Tissue Int. (1994) 54(4):325-326.
73. OURSLER MJ, OSDOBY P, PYFFEROEN J et al.: Avian osteoclasts as estrogen target cells. Proc. Natl. Acad. Sci. USA (1991) 88(15):6613-6617.
74. SPELSBERG TC, SUBRAMANIAM M, RIGGS BL, KHOSLA S: The actions and interactions of sex steroids and growth factors/cytokines on the skeleton. Mol. Endocrinol. (1999) 13(6):819-828.
75. FALAHATI-NINI A, RIGGS BL, ATKINSON EJ et al.: Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. (2000) 106(12):1553-1560.
76. LEDER BZ, LEBLANC KM, SCHOENFELD DA et al.: Differential effects ofandrogens and estrogens on bone turnover in normal men. J. Clin. Endocrinol. Metab. (2003) 88(1):204-210.
77. KHOSLA S, MELTON III LJ, RIGGS BL: Clinical review 144: estrogen and the male skeleton. J. Clin. Endocrinol. Metab. (2002) 87(4):1443-1450.
78. CARLSEN CG, SOERENSEN TH, ERIKSEN EF: Prevalence of low serum estradiol levels in male osteoporosis. Osteoporos. Int. (2000) 11(8):697-701.
79. GENNARI L, MERLOTTI D, MARTINI G et al.: Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J. Clin. Endocrinol. Metab. (2003) 88(11):5327-5333.
80. CARLSTROM K, STEGE R, HENRICKSSON P et al.: Possible bone-preserving capacity of high-dose depot estrogen as compared to orchidectomy in the treatment of patients with prostatic carcinoma. Prostate (1997) 31(3):193-197.
81. ERIKSSON S, ERIKSSON A, STEGE R, CARLSTROM K: Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens. Calcif. Tissue Int. (1995) 57(2):97-99.
82. HOFBAUER LC, SCHOPPET M: Clinical implications of the osteoprotegerin/ RANKL/RANK system for bone and vascular diseases. J. Am. Med, Assoc. (2004) 292(4):490-495.
83. DIAMOND T, CAMPBELL J, BRYANT C et al.: The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma: longitudinal evaluation and response to intermittent cyclic etidronate therapy. Cancer (1998) 83(8):1561-1566.
84. MAILLEFERT JF, SIBILIA J, MICHEL F et a.: Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma. J. Urol. (1999) 161:1219-1222.
85. DANIELL HW: Osteoporosis after orchiectomy for prostate cancer. J. Urol. (1997) 157(2):439-444.
86. SMITH MR, McGOVERN FJ, ZIETMAN AL et al.: Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N. Engl J. Med. (2001) 345:948-955.
87. BERRUTI A, DOGLIOTTI L, TERRONE C et al.: Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy. J. Urol. (2002) 167:2361-2367.
88. SMITH MR, EASTHAM J, GLEASON D et al.: Randomized controlled trial of zoledronic acid to prevent bone loss in men undergoing androgen deprivation therapy for nonmetastatic prostate cancer. J. Urol. (2003) 169:2008-2012.
89. SMITH MR, FALLON MA, LEE H et al.: Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J. Clin. Endocrinol. Metab. (2004) 89:3841-3846,
90. LEE H, McGOVERN K, FINKELSTEIN JS et al.: Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate cancer. Cancer (2005) 104(8):1633-1637.
91. SMITH MR, LEE WC, KRUPSKI T et al.: Association between androgen deprivation therapy and fracture risk: a population-based cohort study in men with nonmetastatic prostate cancer. Proc. Am. Soc. Clin. Oncol. USA (2004) (Abstract 4507).
92. SHAHINIAN VB, KUO YF, FREEMAN JL, GOODWIN JS: Risk of fracture after androgen deprivation for prostate cancer. N. Engl. J. Med. (2005) 352(2):154-164.
93. SMITH M, BOYCE S, MOYNEUR E et al.: Risk of clinical fracture after gonadotropin-releasing hormone agonist therapy for prostate cancer. J. Urol. (2006) 175(1):136-139 (Discussion 139).
94. SMITH M, LEE W, BRANDMAN J et al.: Gonadotropin-releasing hormone (GnRH) agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J. Clin. Oncol. (2005) 23(31):7897-7903.
95. TOWNSEND MF, SANDERS WH, NORTHWAY RO et al.: Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. Cancer (1997) 79:545-550.
96. HATANO T, OISHI Y, FURUTA A et al.: Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer [in process citation], BJU Int. (2002) 86:449-452.
97. OEFELEIN MG, RICCHUITI V, CONRAD W et al.: Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. J. Urol. (2001) 166:1724-1728.
98. MELTON LJ III, ALOTHMAN KI, KHOSLA S et al.: Fracture risk following bilateral orchiectomy. J. Urol. (2003) 169:1747-1750.
99. DICKMAN PW, ADOLFSSON J, ASTROM K, et al: Hip fractures in men with prostate cancer treated with orchiectomy. J. Urol. (2004) 172:2208-2212.
100. TEILLAC P, BONO AV, IRANI J, WIRTH MP, ZLOTTA AR: The role of luteinizing hormone-releasing therapy in locally advanced prostate cancer and biochemical failure: considerations for optimal use. Clin. Ther. (2005) 27(3):273-285.
101. ETTINGER B, BLACK DM, MITLAK BH et al.: Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. J. Am. Med. Assoc. (1999) 282(7):637-645.
102. Evista® (raloxifene citrate), tablet product information: Physician's Desk Reference, 59th Edition, Thompson PDR, Montvale, NJ, USA (2005):1915-1919.
103. Nolvadex® (tamoxifen citrate), tablet product information: Physician's Desk Reference, 59th Edition, Thompson PDR, Montvale, NJ, USA (2005):662.
104. Fareston® (toremifene citrate), tablet product information: Physician's Desk Reference, 59th Edition, Thompson PDR, Montvale, NJ, USA (2005):3139-3141.
105. JOHANSEN AM: Breast cancer chemoprevention: a review of selective estrogen receptor modulators. Clin. J. Oncol. Nurs. (2005) 9(3)317-320.
106. DUNN BK, FORD LG: From adjuvant therapy to breast cancer prevention: BCPT and STAR. Breast J. (2001) 7(3):144-157.
107. MAHAKALA A, THOUTREDDY S, KLEEREKOPER M: Prevention and treatment of postmenopausal osteoporosis. Treat. Endocrinol. (2003) 2(5):331-345.
108. TERMINE JD, WONG M: Post-menopausal women and osteoporosis: available choices for maintenance of skeletal health. Maturitas (1998) 30(3):241-245.
109. NEUBAUER BL, McNULTY AM, CHEDID M et al.: The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model. Cancer Res. (2003) 63(18):6056-6062.
110. waf1/cip1. Prostate (1998) 37:51-59.
111. EL ETREBY MF, LIANG Y, LEWIS RW: Induction of apoptosis by mifepristone and tamoxifen in human LNCaP prostate cancer cells in culture. Prostate (2000) 43(1):31-42.
112. KIM IY, SEONG DO H, KIM BC et al.: Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell lines LNCaP through an androgen-independent pathway. Cancer Res. (2002) 62(13):3649-3653.
113. KIM IY, KIM BC, SEONG DO H et al.: Raloxifene, a mixed estrogen agonist/ antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines. Cancer Res. (2002) 62(18):5365-5369.
114. WOODHAM C, BIRCH L, PRINS GS: Neonatal estrogen down-regulates prostatic androgen receptor through a proteosome-mediated protein degradation pathway. Endocrinology (2003) 144(11):4841-4851.
115. NELLEMANN C, DALGAARD M, HOLST B et al.: Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor. Mol. Cell Endocrinol. (2005) 237(1-2):25-35.
116. ZENG Y, YOKOHIRA M, SAOO K et al.: Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor. Carcinogenesis (2005) 26(6):1109-1116.
117. KAWASHIMA H, TANAKA T, CHENG JS, et al.: Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells. Urol. Res. (2004) 32(6):406-410.
118. MA ZS, HUYNH TH, NG CP, DO PT, NGUYEN TH, HUYNH H: Reduction of CWR22 prostate tumor xenograft growth by combined tamoxifen-quercitin treatment is associated with inhibition of angiogenesis and cellular proliferation. In. J. Oncol. (2004) 24(5):1297-1304.
119. RAGHOW S, HOOSHDARAN MZ, KATIYAR S, STEINER MS: Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model. Cancer Res. (2002) 62:1370-1376.
120. GREENBERG NM, DEMAYO F, FINEGOLD MJ et al.: Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA (1995) 92:3439-3443.
121. KAPLAN-LEFKO PJ, CHEN TM, ITMANN MM et al.: Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model. Prostate (2003) 55(3):219-237.
122. STEINER MS, POUND CR: Phase ILA clinical trial to test the efficacy and the safety of toremifene in men with high-grade prostatic intraepithelial neoplasia. Clin. Prostate Cancer (2003) 2:24-31.
123. FDA: Summary basis of approval, toremifene citrate (Fareston) (1997).
124. SIPILA H, NANTO V, KANGAS L et al.: Binding of toremifene to human serum proteins. Pbarmacol. Toxicol. (1988) 63(1):62-64.
125. KANGAS L: Biochemical and pharmacological effects of toremifene and metabolites. Cancer Chemother. Pharmacol. (1990) 270(1):8-12.
126. BERTHOU F, DREANO Y, BELLOC C, KANGAS L, GAUTIER JC, BEAUNE P: Involvement of cytochrome P450 3A enzyme family in the major metabolic pathways of toremifene in human liver microsomes. Biochem. Pharmacol. (1994) 47(10):1883-1895.
127. SIPILA H, KANGAS L, VUORILEHTO L. et al.: Metabolism of toremifene in the rat. J. Steroid Biochem. (1990) 36(3):211-215.
128. ANTTILA M, VALAVAARA R, KIVINEN S, MAENPAA J: Pharmacokinetics of toremifene. J. Steroid Biochem. (1990) 36(3):249-252.
129. TOMINAGA T, ABE O, IZUO M, NOMURA Y: A phase I study of toremifene. Breast Cancer Res. Treat. (1990) 16:S27-S29.
130. MORELLO KC, WURZ GT, DEGREGORIO MW: Pharmacokinetics of selective estrogen modulators. Clin. Pharmacokinet. (2003) 42(4):361-372.
131. TARAS TL, WURZ GT, LINARES GR, DEGREGORIO MW. Clinical pharmacokinetics of toremifene. Clin. Pharmacokinet. (2000) 39(5):327-334.
132. WISEMAN LR, GOA KL: Toremifene. A review of its pharmacological properties and clinical efficacy in the management of advanced breast cancer. Drugs (1997) 54(1):141-160.
133. KOHLER PC, HAMM JT, WIEBE VJ, DE GREGORIO MW, SHEMANO I, TORMEY DC: Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. Breast Cancer Res. Treat. (1990) 16:S19-S26.
134. BISHOP J, MURRAY R, WEBSTER L et al: Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. Cancer Chemother. Pharmacol. (1992) 30(3):174-178.
135. WIEBE VJ, BENZ CC, SHEMANO I et al.: Pharmacokinetics of toremifene and its metabolites in patients with advanced breast cancer. Cancer Chemother. Pharmacol. (1990) 25(4):247-251.
136. ANTTILA M, LAAKSO S, NYLANDEN P, SOTANIEMI EA: Pharmacokinetics of the novel antiestrogenic agent toremifene in subjects with altered liver and kidney function. Clin. Pharmacol. Ther. (1995) 57(6):628-635.
137. KIVISTO KT, VILLIKKA K, NUMAN L, ANTTILA M, NEUVONEN PJ: Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin. Clin. Pharmacol. Ther. (1998) 64(6):648-654.
138. WURZ GT, SOC L, EMSHOFF VD, CADMAN TB, DEGREGORIO MW: Pharmacokinetic analysis of high-dose toremifene in combination with doxorubicin. Cancer Chemother. Pharmacol. (1998) 42(5):363-366.
139. MAENPAA JU, ALA-FOSSI SL: Toremifene in postmenopausal breast cancer. Efficacy, safety, and cost. Drugs Aging (1997) 11(4):261-270.
140. HOLLI K, VALAVAARA R, BLANCO G et al.: Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer. Finnish Breast Cancer Group. J. Clin. Oncol. (2000) 18(20):3487-3494.
141. STEIN S, ZOLTICK B, PEACOCK T et al.: Phase II trial of toremifene in androgen-independent prostate cancer: a Penn cancer clinical trials group trial. Am. J. Clin. Oncol. (2001) 24(3):283-285.
142. STEIN B, ZINNER N, ISRAELI RS, WAKE R, MITCHELL J, STEINER MS: Effects of toremifene on hormones in men treated for 1 year in a double-blind, placebo-controlled study. J. Urol. (2005) 173(4):272 (Abstract 1004).
143. PRICE D, STEIN B, SIEBER P et al.: Toremifene for the prevention of prostate cancer among men with high-grade prostatic intraepithelial neoplasia: results of a double-blind, placebo-controlled, Phase IIB clinical trial. J. Clin. Oncol. (2005) 23:106.
144. CLARK RV, HERMANN DJ, CUNNINGHAM GR, WILSON TH, MORRILL BB, HOBBS S: Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5 α-reductase inhibitor. J. Clin. Endocrinol. Metab. (2004) 89(5):2179-2184.
145. KUIPER GJ, KUIPER M, CARLSSON B et al.: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptor α and β. Endocrinology (1997) 138(3):863-870.
146. BRADY H, DOUBLEDAY M, GAYO-FUNG LM et al.: Differential response of estrogen receptors α and β to SP500263, a novel potent selective estrogen receptor modulator. Mol. Pharmacol. (2002) 61(3):562-568.
147. PRICE D, ISRAELI R, BOGER R, STEINER MS: Concentration-dependent estrogen receptor binding profile of toremifene may account for its clinical dose-response profile. J. Urol. (2005) 173(4):274 (Abstract 1012).
148. WEIHUA Z, MAKELA S, ANDERSSON LC et al.: A role for estrogen receptor β in the regulation of growth of the ventral prostate. Proc. Natl. Acad. Sci. USA (2001) 98(11):6330-6335.
149. HARRIS DM, BESSELINK E, HENNING SM et al.: Phytoestrogens induce differential estrogen α- or β-mediated responses in transfected breast cancer cells. Exp. Biol. Med. (Maywood) (2005) 230(8):558-568.
150. STEINER MS, PATTERSON A, ISRAELI R et al.: Toremifene citrate versus placebo for treatment of bone loss and other complications of androgen deptivation therapy in patients with prostate cancer. J. Clin. Oncol. (2004) 22:4065 (Suppl. 4597).