Pharmacokinetics and tolerability of exemestane in combination with raloxifene in postmenopausal women with a history of breast cancer

Breast Cancer Research and Treatment

Volumn 111, Issue 2, 2008, Pages 377-388

  Traina, T A ^a   Poggesi, I ^b   Robson, M ^a   Asnis, A ^b   Duncan, B A ^b   Heerdt, A ^a   Dang, C ^a   Lake, D ^a   Moasser, M ^a   Panageas, K ^a   Borgen, P ^c   Norton, L ^a   Hudis, C ^a   Dickler, M N ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b PFIZER INC   (United States)

^c Maimonides Cancer Center   (United States)

Author keywords

Aromatase inhibitor; Breast cancer; Clinical trial; Exemestane; Prevention; Raloxifene; Selective estrogen receptor modulator

Indexed keywords

AROMATASE INHIBITOR; CALCIUM; CYCLOPHOSPHAMIDE; ESTROGEN RECEPTOR; EXEMESTANE; FLUOROURACIL; METHOTREXATE; PROGESTERONE RECEPTOR; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; VITAMIN D;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BONE PAIN; BREAST CANCER; CANCER ADJUVANT THERAPY; CLINICAL ARTICLE; CLINICAL TRIAL; CONSTIPATION; CONTROLLED CLINICAL TRIAL; DESQUAMATION; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG TOLERABILITY; ESTROGEN BLOOD LEVEL; FATIGUE; FEMALE; HOT FLUSH; HUMAN; INFECTION; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; MOOD DISORDER; MUSCULOSKELETAL PAIN; MYALGIA; NEUROPATHY; PHARMACODYNAMICS; POSTMENOPAUSE; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RASH; SIDE EFFECT; STATISTICAL ANALYSIS; TIME TO MAXIMUM PLASMA CONCENTRATION; VAGINAL DRYNESS; WEIGHT GAIN;

AGED; ANDROSTADIENES; AROMATASE INHIBITORS; BREAST NEOPLASMS; DRUG THERAPY, COMBINATION; ESTRADIOL; ESTRONE; FEMALE; HUMANS; MIDDLE AGED; POSTMENOPAUSE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATORS;

EID: 48149101970     PISSN: 01676806     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10549-007-9787-1     Document Type: Article

References (61)

1. Clemons M, Goss P (2001) Estrogen and the risk of breast cancer. N Engl J Med 344:276-285
2. Cauley JA, Lucas FL, Kuller LH et al (1999) Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Study of Osteoporotic Fractures Research Group. Ann Intern Med 130:270-277
3. Osborne CK (1998) Tamoxifen in the treatment of breast cancer. N Engl J Med 339:1609-1618
4. Early Breast Cancer Trialists' Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351:1451-1467
5. Fisher B, Costantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 90:1371-1388
6. Fisher B, Costantino JP, Wickerham DL et al (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97:1652-1662
7. King MC, Wieand S, Hale K et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286:2251-2256
8. Cuzick J (2002) First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 360:817-824
9. Cuzick J, Powles T, Veronesi U et al (2003) Overview of the main outcomes in breast-cancer prevention trials. Lancet 361:296-300
10. Black L, Sato M, Rowley E (1994) Raloxifene (LYI39481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine by-pertrophy in ovariectomized rats. J Clin Invest 93:63-69
11. Delmas PD, Bjarnason NH, Mitlak BH et al (1997) Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337:1641-1647
12. Ettinger B, Black DM, Mitlak BH et al (1999) 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. JAMA 282:637-645
13. Cummings SR, Eckert S, Krueger KA et al (1999) The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 281:2189-2197
14. Cauley JA, Norton L, Lippman ME et al (2001) Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple Outcomes of Raloxifene Evaluation. Breast Cancer Res Treat 65:125-134
15. Cummings SR, Duong T, Kenyon E et al (2002) Serum estradiol level and risk of breast cancer during treatment with raloxifene. JAMA 287:216-220
16. Lippman ME, Krueger KA, Eckert S et al (2001) Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the Multiple Outcomes Of Raloxifene Evaluation study participants. J Clin Oncol 19:3111-3116
17. Martino S, Cauley JA, Barrett-Connor E et al (2004) Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 96:1751-1761
18. Vogel VG, Costantino JP, Wickerham DL et al (2006) Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295:2727-2741
19. Gruber CJ, Tschugguel W, Schneeberger C et al (2002) Production and actions of estrogens. N Engl J Med 346:340-352
20. Simpson ER, Dowsett M (2002) Aromatase and its inhibitors: significance for breast cancer therapy. Recent Prog Horm Res 57:317-338
21. De Jong P, Van de Ven J, Nortier J et al (2002) Inhibition of intratumoral aromatase and estradiol by exemestane in postmenopausal breast cancer patients: results of a double blind randomized study [abstract 268]. Breast Cancer Res Treat 76:S76
22. de Jong P, van de Ven J, Nortier H et al (1997) Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole. Cancer Res 57:2109-2111
23. Buzdar A, Howell A (2001) Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer. Clin Cancer Res 7:2620-2635
24. Miller WR (1999) Biology of aromatase inhibitors: pharmacology/ endocrinology within the breast. Endocr Relat Cancer 6:187-195
25. Miller WR, Dixon JM (2002) Endocrine and clinical endpoints of exemestane as neoadjuvant therapy. Cancer Control 9:9-15
26. Miller W, Dixon J, Grattage L, Stuart M, Hocdtin-Boes G (1999) Effects of neoadjuvant treatment with the aromatase inhibitor, anastrozole (Arimidex) on peripheral and in situ estrogen synthesis and uptake by breast tissue in postmenopausal women. Paper presented at San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 1999
27. Miller WR, Dixon JM (2001) Local endocrine effects of aromatase inhibitors within the breast. J Steroid Biochem Mol Biol 79:93-102
28. Geisler J, King N, Anker G et al (1998) In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 4:2089-2093
29. Geisler J, Haynes B, Anker G et al (2002) Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 20:751-757
30. Geisler J, King N, Dowsett M et al (1996) Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer 74:1286-1291
31. Coombes R, Kilburn L, Snowdon C et al (2007) Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369:559-570
32. Goss PE, Ingle JN, Martino S et al (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793-1802
33. The ATAC Trialists' Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer; first results of the ATAC randomised trial. Lancet 359:2131-2139
34. Lu Q, Liu Y, Long BJ et al (1999) The effect of combining aromatase inhibitors with antiestrogens on tumor growth in a nude mouse model for breast cancer. Breast Cancer Res Treat 57:183-192
35. Brodie A, Jelovac D, Long BJ (2003) Predictions from a preclinical model: studies of aromatase inhibitors and antiestrogens. Clin Cancer Res 9:455S-459S
36. Brodie A, Lu Q, Liu Y et al (1998) Preclinical studies using the intratumoral aromatase model for postmenopausal breast cancer. Oncology (Huntingt) 12:36-40
37. Brodie AH, Mouridsen HT (2003) Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy. Am J Clin Oncol 26:S17-S26
38. Brodie A (2003) Aromatase inhibitor development and hormone therapy: a perspective. Semin Oncol 30:12-22
39. Long BJ, Jelovac D, Handratta V et al (2004) Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. J Natl Cancer Inst 96:456-465
40. Jelovac D, Macedo L, Handratta V et al (2004) Effects of exemestane and tamoxifen in a postmenopausal breast cancer model. Clin Cancer Res 10:7375-7381
41. Jelovac D, Long B, Sabnis G et al (2002) Preclinical studies evaluating the anti-tumor effects of exemestane using the intratumoral aromatase postmenopausal breast cancer model. Breast Cancer Res Treat 76:S77
42. Zaccheo T, Diudici D, di Salle E (1993) Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA induced mammary tumors in rats. J Steroid Biochem Mol Biol 44:677-680
43. di Salle E, Geroni C, Lamparelli M et al (2002) Chemopreventive effect of the aromatase inactivator exemestane combined with the antiestrogen raloxifene in the dimethylbenzanthracene (DMBA)-induced mammary tumors in rats. Am Soc Clin Oncol 21:117a
44. Ingle J, Suman V, Johnson P et al (1999) Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer. Clin Cancer Res 5:1642-1649
45. Rivera E, Valero V, Francis D et al (2004) Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen. Clin Cancer Res 10:1943-1948
46. Baum M, Budzar AU, Cuzick J et al (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359:2131-2139
47. Hutson PR, Love RR, Havighurst TC et al (2005) Effect of exemestane on tamoxifen pharmacokinetics in postmenopausal women treated for breast cancer. Clin Cancer Res 11:8722-8727
48. Swain S, Wilson J, Eleftherios M et al (2004) Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. J Natl Cancer Inst 9:516-523
49. Chen Q, Ngui JS, Doss GA et al (2002) Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation. Chem Res Toxicol 15:907-914
50. Johannessen DC, Engan T, Di Salle E et al (1997) Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study. Clin Cancer Res 3:1101-1108
51. Cenacchi V, Baratte S, Cicioni P et al (2000) LC-MS-MS determination of exemestane in human plasma with heated nebulizer interface following solid-phase extraction in the 96 well plate format. J Pharm Biomed Anal 22:451-460
52. Hochner-Celnikier D (1999) Pharmacokinetics of raloxifene and its clinical application. Eur J Obstet Gynecol Reprod Biol 85:23-29
53. Goss P, Bondarenko I, Manikhas G et al (2006) Phase 3 study of atamestane + toremifene vs. letrozole in advanced breast cancer. J Clin Oncol 24:LBA525
54. Langecker P, Blanchett D, Lang W et al (2002) Phase I, open-label, randomized, crossover study of the pharmacokinetic interaction of toremifene and atamestane (Biomed 777) in healthy postmenopausal women. Paper presented at Breast Cancer Res Treat, San Antonio, TX, December 11-14, 2002
55. Masamura S, Santner SJ, Heitjan DF et al (1995) Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab 80:2918-2925
56. Baum M, on behalf of the ATAC Trialists' Group (2001) The ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant breast cancer trial in postmenopausal women. Breast Cancer Res Treat 69:210
57. Dowsett M, Cuzick J, Howell A et al (2001) Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and Tamoxifen Alone or in Combination' (ATAC) trial. Br J Cancer 85:317-324
58. Lonning PE, Bajetta E, Murray R et al (2000) Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol 18:2234-2244
59. Dimitrakakis C, Zhou J, Wang J et al (2003) A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause 10:292-298
60. Barrett-Connor E, Mosca L, Collins P et al (2006) Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 355:125-137
61. Vogel VG, Costantino JP, Wickerham DL et al (2003) National Surgical Adjuvant Breast and Bowel Project update: prevention trials and endocrine therapy of ductal carcinoma in situ. Clin Cancer Res 9:495S-501S