Orally administered Endoxifen is a new therapeutic agent for breast cancer

Breast Cancer Research and Treatment

Volumn 122, Issue 2, 2010, Pages 579-584

  Ahmad, Ateeq ^a   Ali, Shoukath M ^a   Ahmad, Moghis U ^a   Sheikh, Saifuddin ^a   Ahmad, Imran ^a  

^a Jina Pharmaceuticals Inc   (United States)

Author keywords

Breast cancer; CYP2D6.; Efficacy; Endoxifen

Indexed keywords

ENDOXIFEN; TAMOXIFEN; TAMOXIFEN DERIVATIVE; UNCLASSIFIED DRUG; 4-HYDROXY-N-DESMETHYLTAMOXIFEN; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG SAFETY; DRUG SYNTHESIS; FEMALE; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; BREAST NEOPLASMS; CELL PROLIFERATION; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; NUDE MOUSE; ORAL DRUG ADMINISTRATION; PATHOLOGY; SPRAGUE DAWLEY RAT; TUMOR CELL LINE; TUMOR VOLUME;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; MICE; MICE, NUDE; RATS; RATS, SPRAGUE-DAWLEY; TAMOXIFEN; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77955661193     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-009-0704-7     Document Type: Article

References (24)

1. E.B.C.T.C. Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351:1451-1467.
2. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (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.
3. Furr BJ, Jordan VC (1984) The pharmacology and clinical uses of tamoxifen. Pharmacol Ther 25:127-205.
4. Kinsinger LS, Harris R, Woolf SH, Sox HC, Lohr KN (2002) Chemoprevention of breast cancer: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137:59-69.
5. Costantino JP, Kuller LH, Ives DG, Fisher B, Dignam J (1997) Coronary heart disease mortality and adjuvant tamoxifen therapy. J Natl Cancer Inst 89:776-782.
6. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30-39.
7. Johnson MD, Zuo H, Lee KH, Trebley JP, Rae JM, Weatherman RV, Desta Z, Flockhart DA, Skaar TC (2004) Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 85:151-159.
8. Holmes F, Liticker JD (2005) Pharmacogenomics of tamoxifen in a nutshell-and who broke the nutcracker? J Oncol Pract 1:155-159.
9. Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Weinshilboum RM, Fritcher EG, Nibbe AM, Desta Z, Nguyen A, Flockhart DA, Perez EA, Ingle JN (2007) The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101:113-121.
10. Schroth W, Antoniadou L, Fritz P, Schwab M, Muerdter T, Zanger UM, Simon W, Eichelbaum M, Brauch H (2007) Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 25:5187-5193.
11. Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95:1758-1764.
12. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48:589-601.
13. Grever MR, Schepartz SA, Chabner BA (1992) The National Cancer Institute: cancer drug discovery and development program. Semin Oncol 19:622-638.
14. Shoemaker RH (2006) The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer 6:813-823.
15. Plowman J, Dykes DJ, Hollingstead M, Simpson-Herren L, Alley MC (1997) Human tumor xenograft models in NCI drug development. In Teicher B (ed) In Anticancer drug development guide: preclinical screening, clinical trials, and approval. Humana Press Inc., Totowa, NJ, chapter 6, pp 101-124.
16. Waud W, Dykes DJ, Hollingshead MG, Camalier RF, Steeg PS, Mayo JG (1999) Characterization of in vivo mammary and prostate tumor xenograft models for growth and response to clinical anticancer agents. In: Fiebig HH, Burger AM (eds) Relevance of tumor models for anticancer drug development. Contributions to oncology, vol 54. Kargel, Basel, pp 305-315.
17. Lazarus P, Blevins-Primeau AS, Zheng Y, Sun D (2009) Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen. Ann N Y Acad Sci 1155:99-111.
18. Daniel P, Gaskell SJ, Bishop H, Campbell C, Nicholson RI (1981) Determination of tamoxifen and biologically active metabolites in human breast tumours and plasma. Eur J Cancer Clin Oncol 17:1183-1189.
19. Adam HK, Douglas EJ, Kemp JV (1979) The metabolism of tamoxifen in human. Biochem Pharmacol 28:145-147.
20. Robinson SP, Langan-Fahey SM, Jordan VC (1989) Implications of tamoxifen metabolism in the athymic mouse for the study of antitumor effects upon human breast cancer xenografts. Eur J Cancer Clin Oncol 25:1769-1776.
21. Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC (2009) The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor a for degradation in breast cancer cells. Cancer Res 69(5):1722-1727.
22. Borges S, Desta Z, Li L, Skaar TC, Ward BA, Nguyen A, Jin Y, Storniolo AM, Nikoloff DM, Wu L, Hillman G, Hayes DF, Stearns V, Flockhart DA (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80(1):61-74.
23. Lash TL, Ahern TP, Cronin-Fenton D, Garne JP, Hamilton-Dutoit S, Kvistgaard ME, Rosenberg CL, Silliman RA, Sørensen HT (2008) Modification of tamoxifen response: what have we learned? J Clin Oncol 26(10):1764-1765.
24. Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Bolander J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302(13):1429-1436.