Anastrozole

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

Like anastrozole, letrozole is a third generation, type II nonsteroidal aromatase inhibitor. Renal excretion of its... 

C15HH1N2 120511-72-0) see Anastrozole A -methyl-o-phenylenediamine (C7HK1N2 4760-34-3) see Telmisartan... 

Anastrozole is a selective nonsteroidal aromatase inhibitor that lowers estrogen levels. The pharmacokinetics of anastrozole demonstrate good absorption, with hepatic metabolism the primary route of elimination and only 10% excreted unchanged by the kidney. The elimination half-life is approximately 50 hours. Anastrozole is used for the adjuvant treatment of postmenopausal women with hormone-positive breast cancer and in breast cancer patients who have had disease progression following tamoxifen. Side effects include hot flashes, arthralgias, osteoporosis/bone fractures, and thrombophlebitis. 

Successful coadministration of bisphosphonates with the aro-matase inhibitors has been accomplished in many patients in the metastatic setting. The three available aromatase inhibitors are exemestane, anastrozole, and letrozole. 

Nonsteroidal Steroidal Anastrozole Letrozole Exemestane 1 mg orally daily 2.5 mg orally daily 25 mg orally daily Hot flashes, arthralgias, myalgias, headaches, diarrhea, mild nausea, osteoporosis (boneloss)... 

Fulvestrant is a new agent approved for the second-line therapy of postmenopausal metastatic breast cancer patients who have tumors that are hormone-receptor-positive. Studies examining the role of fulvestrant in the treatment of metastatic breast cancer have compared this agent with anastrozole. Given anas-trozole s mechanism of action, only postmenopausal women were eligible for these trials. There is no biologic reason why fulvestrant should not produce similar outcomes in premenopausal... 

Options for adjuvant hormonal therapy in postmenopausal women include aromatase inhibitors (e.g. anastrozole, letrozole, or exemestane) either in place of or after tamoxifen. Adverse effects with aromatase inhibitors include hot flashes, myalgia/arthralgia, vaginal dryness/atrophy, mild headaches, and diarrhea. 

Nonsteroidal Anastrozole 1 mg orally daily Hot flashes, arthralgias,... 

Toremifene has similar efficacy and tolerability as tamoxifen and is an alternative to tamoxifen in postmenopausal patients. Fulvestrant is a second-line intramuscular agent with similar efficacy and safety when compared to anastrozole in patients who progressed on tamoxifen. 

Howell A, Robertson JF, Quaresma AJ, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C (2002) Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20 3396-3403... 

Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, et al. (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy results of a North American trial. J Clin Oncol 20 3386-3395... 

Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, et al. (2003) Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women a prospective combined analysis of two multicenter trials. Cancer 98 229-238... 

Finally, raloxifene has been successfully used in a symptomatic premenopausal woman with benign metastasizing leiomyomas (Rivera et al. 2004). In particular, 60 mg/d raloxifene, in coadministration with anastrozole 1 mg/ d, induced a regression of the symptoms within few days, but a worsening of the symptomatology was observed when the woman stopped the treatment (Rivera et al. 2004). Raloxifene (120 mg/d) plus anastrozole (2 mg/d) was again... 

Anastrozole (Arimidex M) Aromatase inhibitor Adjuvant breast Randomized Phase III... 

Aromatase inhibitors (including anastrozole, letrozole, aminoglutethimide, exemestane, formestane, testolactone), selective estrogen receptor modulators—SERMs (including raloxifene, tamoxifen, toremifene), clomiphene, cyclofenil, fulvestrant Diuretics, amiloride, bumetanide, canrenone, chlorthalidone, etacrynic acid, furosemide, indapamide, metolazone, spironolactone, thiazides, triamterene... 

Trastuzumab is licensed for the treatment of early breast cancer that overexpresses human epidermal growth factor receptor-2 (HER2). It may be administered as monotherapy or in combination with, for example, paclitaxel, docetaxel (taxanes) or anastrozole (aromatase inhibitors). Since trastuzumab can cause cardiotoxicity, concomitant use with anthracyclines such as... 

The increasing clinical importance of tamoxifen in the 1980s prompted development of drugs that indirectly target the estrogen receptor, for example the aromatase inhibitor anastrozole (ARIMIDEX ), a selective inhibitor of estrogen biosynthesis [28]. Progress in treatment of hormone-dependent prostate cancer followed advances in breast cancer, with demonstration that... 

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