Aromatase inhibitors anastrozole

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... 

Anastrozole (2) and letrozole (3) are type II aromatase inhibitors. They competitively inhibit the conversion of androgens to estrogens. They are both potent and selective aromatase inhibitors. Anastrozole is the most extensively investigated third-generation aromatase inhibitor. It is very potent, with a daily dose of a mere 1 mg. Its safety profile is well developed all doses evaluated up to 10 mg were well tolerated and no serious adverse events were attributed to it. No clinical or laboratory evidence of adrenal insufficiency was observed. 

Anastrozole. The aromatase inhibitor anastrozole. Ari-midex. 2.2 - 5-( IH-1.2.4-triazxjl-1 -ylmcthyl)-1,3-phenyl-... 

Aromatase inhibitors Anastrozole, letrozole, exemestane Breast cancer... 

Aromatase inhibitors Anastrozole and related compounds (eg, letrozole) are nonsteroidal inhibitors of aromatase, the enzyme required for estrogen synthesis. These drugs are used in the treatment of breast cancer. 

E. Aromatase Inhibitors Anastrozole and letrozole inhibit aromatase, the enzyme that catalyzes the conversion of androstenedione (an androgenic precursor) to estrone (an estrogenic hormone). Both drugs are used in advanced breast cancer. Toxicity includes nausea, diarrhea, hot flushes, bone and back pain, dyspnea, and peripheral edema. 

The postmenopausal client with breast cancer is placed on the aromatase inhibitor anastrozole (Arimidex). Which data indicates the medication is effective ... 

Tamoxifen (Tam) (Novaldex) is an estrogen receptor antagonist present in breast tissue, with activity linked to its metabolite hydroxytamoxifen (OHTam). In other tissues (endometrium) it behaves as an agonist due to the presence of other coactivators. This SERM is involved in the endocrine therapy commonly used with hormone-dependent breast cancers, although aromatase inhibitors (Anastrozole) are also frequently used for the same female patient group. Tamoxifen is the most common hormonal treatment for breast cancer in men. It also protects against osteoporosis [17]. 

Mareck, U., Geyer, H., Guddat, S., et al. Identification of the aromatase inhibitors anastrozole and exemestane in human urine using liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 20,1954-1962. 

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... 

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. 

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. 

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... 

Anastrozole (Arimidex) [Antineoplastic/Nonsteroidal Aromatase Inhibitor] Uses Breast CA postmenopausal w/ met breast CA, adjuvant Rx postmenopausal early hormone-rec tor(+) breast CA Action Selective nonsteroidal aromatase inhibitor, X circ estradiol Dose 1 mg/d Caution [D, ] Contra PRO Disp Tabs SE D, HTN, flushing, t bone/tumor pain, HA, somnolence Interactions None noted EMS May cause vag bleeding during 1st few wks of Tx OD May cause NA, abd discomfort, and bloody stools symptomatic and supportive... 

AROMATASE INHIBITORS FOR BREAST CANCER EXEMESTANE (AROMASIN ), ANASTROZOLE (ARIMIDEX ), AND LETROZOLE (FEMARA )... 

Despite the significant benefit that tamoxifen has bestowed on breast cancer patients, the third-generation aromatase inhibitors are rapidly replacing tamoxifen as the first-Une treatment for breast cancers. In this chapter, focus will be given to three representative small-molecule aromatase inhibitors for breast cancer exemestane (1, Aromasin ), anastrozole (2, Arimidex ), and letrozole (3, Femara ). 

Anastrozole, a selective nonsteroidal inhibitor of aromatase (the enzyme required for estrogen synthesis. Figures 40-2 and 40-5), is effective in some women whose breast tumors have become resistant to tamoxifen (see Chapter 54). Letrozole is similar. Exemestane, a steroid molecule, is an irreversible inhibitor of aromatase. Like anastrozole and letrozole, it is approved for use in women with advanced breast cancer (see Chapter 54). 

Carpal tunnel syndrome has been reported in six patients taking aromatase inhibitors (29). Most subsequently experienced relief after withdrawal and/or switching to tamoxifen. In clinical trials of anastrozole and exemestane, carpal tunnel syndrome occurred in about 3% (30,31,32). 

Lycette JL, Luoh SW, Beer TM, Deloughery TG. Acute bilateral pulmonary emboli occurring while on adjuvant aromatase inhibitor therapy with anastrozole Case report and review of the literature. Breast Cancer Res Treat 2006 99(3) 249-55. 

This study has again confirmed that endometrial problems can be induced by tamoxifen early in the course of treatment and that these problems do not arise with aromatase inhibitors, which may actually reduce the endometrial changes induced by tamoxifen. The idea that the new oral aromatase inhibitors might well replace tamoxifen in breast cancer was tentatively advanced in SEDA-26 (p. 445) and has now been supported by some of the material cited above, as well as by a panel consensus (25). Citing efficacy and safety data on anastrozole, exemestane, and letrozole, the authors concluded that third-generation aromatase inhibitors may be considered first-line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women and may also be used for preoperative therapy of breast cancer. 

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