Tamoxifen medicines

Jordan VC. Tamoxifen a most unlikely pioneering medicine. Nat Rev Drug Discov 2003 2 205-13. 

Journal of Medicine, was compared with placebo in postmenopausal breast cancer patients who had completed 5 years of tamoxifen therapy. After a median follow-up of 2.4 years, letrozole was associated with superior estimated 4-year DFS compared with placebo in this setting (93% vs. 87% p <0.001). While these results were preliminary, patients were unblinded and allowed to crossover to the active arm of therapy. Therefore effects on survival will never be ascertained. However, further follow-up will be completed with regard to safety and DFS in those patients randomized to letrozole from the beginning of the trial. Based on the results of this study, letrozole received FDA approval in November 2004 for extended adjuvant therapy (i.e., after 5 years of tamoxifen therapy). In another recent trial, patients who had completed 2 to 3 years of adjuvant tamoxifen therapy were randomized to continue tamoxifen or crossover to exemestane for the remainder of the 5 years. After a median followup of 30.6 months, DFS was substantially longer with exemestane compared with continuation of tamoxifen (91.5% vs. 86.8% HR = 0.68,p = 0.00005). Concerns regarding long-term safety also arise with this study, with data indicating a possible increase in cardiovascular disease, osteoporosis, and visual disturbances with exemestane compared with tamoxifen. 

Love, R.R., Mazess, R.B., Barden, H.S., Epstein, S., Newcomb, P.A., Jordan, V.C., Carbone, P.P. and DeMets, D.L. (1992) Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. New England Journal of Medicine, 326, 852-856. 

Chao, E.Y., Collins, J.L., Gaillard, S., Miller, A.B., Wang, L., Orhand-Miller, L.A., Nolte, R.T., McDonnell, D.P. et al. (2006) Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRy. Bioorganic el Medicinal Chemistry Letters, 16, 821-824. 

Fallowfield, L.J., Midriewicz, E., Andersen, J., Lonning, P.E., Cocconi, G., Stewart, A., Stuart, N., Snowdon, C.F., Carpentieri, M., Massimini, G. and Bliss, J.M. (2004) The Intergroup Exemestane Study, a randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. The New England Journal of Medicine, 350, 1081-1092. 

Jordan, V.C. (2006) Case histories tamoxifen, in Comprehensive Medicinal Chemistry II (eds J. Taylor and D. Triggle), Elsevier, Oxford, vol. 8 pp. 83-102. 

Margolese, R., Robidoux, A., Shibata, H., Terz, J., Paterson, A.H.G., Feldman, M.I., Farrar, W., Evans, J., Lickley, H.L. and Ketner, M. (1989) A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptorpositive tumors. The New England Journal of Medicine, 320, 479—484. 

Jarman, M. and Foster, A.B. (1989) Derivatives of tamoxifen. Dependence of antiestrogenicity on the 4-substituent. Journal of Medicinal Chemistry, 32, 2527-2533. 

Fnjiki, H., Sngannma, M., Knrnsn, M., Okabe, S., Tanignchi, S., and Yoshida, T. 2003. New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention stndy with EGCG and snlindac or tamoxifen. Mutat. Res. 523/524 119-25. 

The arylation of benzyl ketones has been applied to the synthesis of analogs of tamoxifen, which is a medicinal agent for breast cancer (Eq. 10) [52,53]. 

Tamoxifen and other anti-oestrogens + Herbal medicines... 

Indirect evidence hints at the possibiiity that some herbai medicines that possess oestrogenic activity may oppose the actions of anti-oestrogens, such as tamoxifen, used in the treatment of breast cancer. 

Although this is largely speculative at the moment, the writer of the letter suggests that such herbal medicines are undesirable in patients with breast cancer. In addition to tamoxifen, there are now a number of other drugs used for breast cancer that in one way or another reduce the stimulation of oestrogen receptors (anastrozole, exemestane, letrozole, toremifene). More study is needed. 

A British group has set out to determine the possible effects of consumer information on people s perception of adverse reactions [ ]. The study related specifically to tamoxifen, but the findings could be considered relevant to any form of medicinal therapy. Use of a pop-up on the UK CRUK website recruited 134 users, who were randomly allocated to one of four conditions and asked to imagine they had to take tamoxifen, estimate the risks of four adverse reactions, and indicate a preference for the presentation of information in a particular manner. Those who were presented with absolute frequencies for the occurrence of... 

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