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Anastrozole is a type of new generation endocrine therapy used to treat breast cancer. Specifically, it is an aromatase inhibitor pill for to stop estrogen production. It is used by patients with hormone receptor-positive breast cancer or those at high risk for developing cancer.
It was first approved by the FDA in 1995 and then again in 2000 as a first-line treatment. [1] Common side effects include vasodilation, nausea, pain in the bone. Use during pregnancy is known to harm the baby.
Mechanism of action[edit]
Anastrozole is part of the aromatase inhibitor family which means it reversibly binds to the aromatase enzyme. and through competitive inhibition blocks the conversion of androgens to estrogens in peripheral (extra-gonadal) tissues.[2] In short it works by blocking the production of estrogen.
Market production[edit]
It is a pill taken orally, commonly referred to by under the trade name Arimidex among others. Anastrozole was patented in 1987 and approved for medical use in 1995.[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4]Anastrozole is available as a generic medication.[2] The wholesale cost in the developing world is about 1.92 to 30.60 USD a month.[6] In the United States, the wholesale cost is about 3.81 USD per month.[7]
Medical uses[edit]
Breast Cancer[edit]
Newer endocrine therapies have developed in the recent years because of Tamoxifen, which was the originally most popular and thought to be the most effective drug, built up resistance in patients (Ohno).
The ATAC trial was of localized breast cancer and women received either anastrozole, tamoxifen, or both for five years, followed by five years of follow-up.[5] After more than 5 years the group that received anastrozole had better results than the tamoxifen group.[5] The trial suggested that anastrozole is the preferred medical therapy for postmenopausal women with localized breast cancer, which is estrogen receptor (ER) positive.[5] Another study found that the risk of recurrence was reduced by 40%, but was associated with an increased risk of bone fractures. The study concluded that ER positive patients benefited from switching from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.[6] A more recent trial found that anastrozole significantly reduced the incidence of breast cancer in postmenopausal women relative to placebo, and while there were side effects related to estrogen deprivation observed, the researchers concluded that this was probably not related to the treatment. Lead author Jack Cuzick was quoted by the BBC as saying, "This class of drugs is more effective than previous drugs such as tamoxifen and crucially, it has fewer side effects," adding that he thought there was now enough evidence to support offering the drug.[3]
Combination Therapy[edit]
A correlation study in 2002 found that Anastrozole is more effective alone than when used in combination with Tamoxifen [7] Fulvestrant and Anastrozole were given in combination therapy trials, which found the combination therapy to be more effective than each medication alone, or when given sequentially. [8]Currently, there is no clinical evidence to show that Anastrozole in combination with Fulvestrant had a clinical advantage over anastrozole monotherapy in patients with a history of previous adjuvant anti-estrogen exposure.[9]
Side Effects[edit]
Common side effects are an altered mood, coughing, hot flashes, and nausea. Many reports of general, bone, joint and back pain have been seen. More severe side effects are vasodilation, osteoporosis and, bone loss[10] An increased risk for heart disease and bone fracture is also recorded[11].
Other uses[edit]
In Females[edit]
Recent studies have begun using aromatase inhibitors to treat other female diseases, such as endometriosis. There has been positive feedback that indicate that it allows for better control in late-stage disease. [12]
In men[edit]
AnastrozoAnastrozole has been tested for reducing estrogens, including estradiol, in men.[4] Excess estradiol in men can cause benign prostatic hyperplasia, gynecomastia, and symptoms of hypogonadism. It can also contribute to increased risk of stroke, heart attack, chronic inflammation, prostate enlargement and prostate cancer.[13] Some athletes and body builders use anastrozole as part of their steroid cycle to reduce and prevent symptoms of excess estrogen--gynecomastia, emotional lability and water retention.[4] Study data suggest dosages of 0.5 mg to 1 mg a day reduce serum estradiol by approximately 50% in men, which differs in postmenopausal women.[14] Anastrozole has also proven to be efficient in increasing testosterone production in elderly males. This opens the potential for Anastrozole to be used as an androgen replacement therapy in the future. [15]
In children[edit]
Anastrozole may be used off-label in children with precocious puberty, or children with pubertal gynecomastia.[16]Aromatase inhibitors, in combination with an antiandrogen are effective in preventing bone age advancement and virilization in boys with FMPP. [17] Following the onset of puberty, the epiphyseal plate begins to close due to an increased amount of estrogen production escaping local metabolism and spreading to the circulatory system.[16] It is shown to help slow this process, and increase adult height prediction in adolescent males treated with protein-based peptide hormones for the treatment of growth hormone deficiency.[18]
- ^ Xanthopoulos, J. M.; Romano, A. E.; Majumdar, S. K. (2005). "Response of Mouse Breast Cancer Cells to Anastrozole, Tamoxifen, and the Combination". Journal of Biomedicine & Biotechnology. 2005 (1): 10–19. doi:10.1155/JBB.2005.10. ISSN 1110-7251. PMC 1138270. PMID 15689634.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b Simpson ER (September 2003). "Sources of estrogen and their importance". J. Steroid Biochem. Mol. Biol. 86 (3–5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515.
- ^ a b Gallagher, James (12 December 2013). "Breast cancer: Drug 'halves' risk of tumours". BBC News. Retrieved 12 December 2013.
- ^ a b c Mauras N, O'Brien KO, Klein KO, Hayes V (July 2000). "Estrogen suppression in males: metabolic effects". J. Clin. Endocrinol. Metab. 85 (7): 2370–7. doi:10.1210/jc.85.7.2370. PMID 10902781.; Dougherty RH, Rohrer JL, Hayden D, Rubin SD, Leder BZ (February 2005). "Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels". Clin. Endocrinol. (Oxf). 62 (2): 228–35. doi:10.1111/j.1365-2265.2005.02205.x. PMID 15670201.
- ^ a b c Howell A; Cuzick J; Baum M; et al. (2005). "Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer". Lancet. 365 (9453): 60–2. doi:10.1016/S0140-6736(04)17666-6. PMID 15639680.
- ^ Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J (2005). "Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial". Lancet. 366 (9484): 455–62. doi:10.1016/S0140-6736(05)67059-6. PMID 16084253.
- ^ "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". The Lancet. 359 (9324): 2131–2139. 2002-06-22. doi:10.1016/s0140-6736(02)09088-8. ISSN 0140-6736.
- ^ Mehta, Rita S.; Barlow, William E.; Albain, Kathy S.; Vandenberg, Ted A.; Dakhil, Shaker R.; Tirumali, Nagendra R.; Lew, Danika L.; Hayes, Daniel F.; Gralow, Julie R.; Livingston, Robert B.; Hortobagyi, Gabriel N. (2 August 2012). "Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer". New England Journal of Medicine. 367 (5): 435–444. doi:10.1056/NEJMoa1201622.
- ^ Bergh, Jonas; Jönsson, Per-Ebbe; Lidbrink, Elisabet Kerstin; Trudeau, Maureen; Eiermann, Wolfgang; Brattström, Daniel; Lindemann, Justin P.O.; Wiklund, Fredrik; Henriksson, Roger (June 2012). "FACT: An Open-Label Randomized Phase III Study of Fulvestrant and Anastrozole in Combination Compared With Anastrozole Alone As First-Line Therapy for Patients With Receptor-Positive Postmenopausal Breast Cancer". Journal of Clinical Oncology. 30 (16): 1919–1925. doi:10.1200/jco.2011.38.1095.
- ^ Iwata, Hiroji; Masuda, Norikazu; Ohno, Shinji; Rai, Yoshiaki; Sato, Yasuyuki; Ohsumi, Shozo; Hashigaki, Satoshi; Nishizawa, Yoshinori; Hiraoka, Masahiro (2013-06-01). "A randomized, double-blind, controlled study of exemestane versus anastrozole for the first-line treatment of postmenopausal Japanese women with hormone-receptor-positive advanced breast cancer". Breast Cancer Research and Treatment. 139 (2): 441–451. doi:10.1007/s10549-013-2573-3. ISSN 0167-6806. PMC 3669502. PMID 23715630.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Lester, James E.; Dodwell, David; Purohit, Omprakash P.; Gutcher, Sandra A.; Ellis, Susan P.; Thorpe, Ruth; Horsman, Janet M.; Brown, Janet E.; Hannon, Rosemary A. (2008-09-30). "Prevention of Anastrozole-Induced Bone Loss with Monthly Oral Ibandronate during Adjuvant Aromatase Inhibitor Therapy for Breast Cancer". Clinical Cancer Research. 14 (19): 6336–6342. doi:10.1158/1078-0432.ccr-07-5101.
- ^ Bogliolo, Stefano; Gardella, Barbara; Dominoni, Mattia; Musacchi, Valentina; Cassani, Chiara; Zanellini, Francesca; De Silvestri, Annalisa; Gaggero, Chiara Roberta; Babilonti, Luciana; Spinillo, Arsenio (15 December 2015). "Effectiveness of aromatase inhibitors in the treatment of advanced endometrial adenocarcinoma". Archives of Gynecology and Obstetrics. 293 (4): 701–708. doi:10.1007/s00404-015-3974-9.
- ^ Faloon, William. "Dangers of Excess Estrogen In the Aging Male". Life Extension Magazine, November 2008. [1]
- ^ Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C (March 2004). "Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels". J. Clin. Endocrinol. Metab. 89 (3): 1174–80. doi:10.1210/jc.2003-031467. PMID 15001605.
- ^ . doi:10.1210/jc.2003-031467.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ a b Faglia G, Arosio M, Porretti S (December 2000). "Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up?". J. Endocrinol. Invest. 23 (11): 721–3. doi:10.1007/bf03345059. PMID 11194703.
- ^ . doi:10.1097/MOP.0b013e32833ab888.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ Mauras N, Gonzalez de Pijem L, Hsiang HY, Desrosiers P, Rapaport R, Schwartz ID, Klein KO, Singh RJ, Miyamoto A, Bishop K (March 2008). "Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years". J. Clin. Endocrinol. Metab. 93 (3): 823–31. doi:10.1210/jc.2007-1559. PMC 2266949. PMID 18165285.