Tamoxifen side effects

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. 

Jones J. Tamoxifen side effects may be attributable to other causes. J Natl Cancer Inst 2001 93(l) ll-2. 

Tamoxifen side effects include headaches, depression, stomach irritation, vaginal discharge, constipation, shortness of breathe (rare), loss of vision (rare), and swelling of the hands and lower legs. 

Knapp P, Gardner PH, Raynor DK, Woolf E, McMillan B. Perceived risk of tamoxifen side effects a study of the use of absolute frequencies or frequency bands, with or without verbal descriptors. Patient Educ Counsell 2010 79 267-71. 

Aromatase inhibitors are relatively well tolerated however have a number of distinct side effects are observed that stem from the state of estrogen deprivation induced by aromatase inhibitors. Side effects include hot flashes, joint and muscle aches, vasomotor symptoms and vaginal dryness. Variable effects of aromatase inhibitors on lipid levels have been observed. Trials comparing third generation aromatase inhibitors to tamoxifen have also repotted an increased risk of cardiovascular events in the group receiving aromatase inhibitors. 

Exemestane is an irreversible aromatase inactivator that binds to the aromatase enzyme to block the production of estrogen from androgens. Exemestane is absorbed rapidly after oral administration, with a terminal half-life of 24 hours. The drug is eliminated primarily by the liver and feces, with less than 1% of the dose excreted unchanged in the urine. Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women who have had disease progression following tamoxifen therapy. Side effects include hot flashes, fatigue, osteoporosis/bone fractures, and flulike symptoms. 

Toremifene is a recently marketed antiestrogen whose primary advantage is a lower estrogenic antiestrogenic ratio than tamoxifen (based on laboratory data).41 Toremifene (60 mg orally daily) has been found to have efficacy similar to that of tamoxifen in metastatic disease and a generally similar side-effect profile.42 Currently, toremifene is indicated as an alternative to tamoxifen in patients with metastatic breast cancer, but studies are ongoing that evaluate its safety and efficacy in the adjuvant setting. 

Tamoxifen is the antiestrogen of choice in premenopausal women whose tumors are hormone-receptor positive, unless metastases occur within 1 year of adjuvant tamoxifen. Maximal beneficial effects do not occur for at least 2 months. In addition to the side effects described for adjuvant therapy, tumor flare or hypercalcemia occurs in approximately 5% of patients with MBC. 

The effects of pure antiestrogens in the uterus have also been extensively studied, since it is an estrogen-dependent organ and the target of the main side effects of tamoxifen therapy, such as endometrial hyperplasia, hypertrophy of glandular epithelium, or even focal cellular atypia (Sourla et al. 1997). 

Tamoxifen users present also a doubling incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) (118 vs. 62 cases). This increase is similar to that seen with HRT. There are some aspects of this side effect that should be commented on to improve the management of women eligible for tamoxifen treatment and at risk for DVT (Goldhaber 2005). In the subanalysis of the Italian study (Decensi et al. 2005), the venous thromboembolism definition included DVT, PE, and superficial phlebitis. Most of the VTE that the authors reported were, in fact, cases of superficial phlebitis, whereas the admitted definition of venous thromboembolism excludes this entity. Such conceptual differences, together with differences in age and background characteristics between the four studies, can explain the diversity in the incidences observed. 

Berliere M, Charles A, Galant C, Donnez J (1998) Uterine side effects of tamoxifen a need for systematic pretreatment screening. Obstet Gynecol 91 40-44... 

The most commonly observed side effect in patients taking raloxifene or tamoxifen was hot flashes (Agnusdei 1999 Muchmore 2000 Miller 2002). In the study by Mounts et al. (2002) in breast cancer patients < 56 years of age, the most frequent complaints during tamoxifen treatment were hot flashes (85%) and disturbed sleep (55%), whereas in the CORE study (Martino et al. 2004) hot flashes were observed in 12.5% of the raloxifene group vs. 6.9% in the placebo group. 

Tamoxifen is on oestrogen-receptor antagonist. It is used in post-menopousol women with oestrogen-receptor-positive metastatic breast cancer at a dose of 20 mg doily. It con also be used in combination with chemotherapy. Severe side-effects ore infrequent however, it is associated with a small risk of endometrial cancer. Patients should be informed and reassured that the benefits of the treatment at this dose outweigh the risk. 

Tamoxifen is an oestrogen-receptor antagonist indicated as adjuvant hormonal treatment in oestrogen-receptor-positive breast cancer in postmenopausal women. Common side-effects include alopecia and uterine fibroids. 

Resistance to tamoxifen is a complex phenomenon and there is evidence that relapse under tamoxifen therapy is linked to the estrogenicity of the drug. Both, the great success of tamoxifen and its liabilities have boosted the search for new analogues in the past 25 years with the goal of identifying a compoimd with increased anti-tumour activity and with reduced side effects. A second generation of structurally related triphenyl-ethylenes like... 

Tamoxifen administration is associated with few toxic side effects, most frequently hot flashes (in 10-20% of patients) and occasionally vaginal dryness or discharge. Mild nausea, exacerbation of bone pain, and hypercalcemia may occur. 

Another therapeutic role for estrogens is in the treatment of cancer. In androgen-dependent prostate carcinoma, estrogens are used therapeutically to suppress androgen formation and thus tumor growth. Estrogens are also used to treat inoperable breast cancer in men and postmenopausal women. However, antiestrogens, such as tamoxifen, have fewer side effects and are usually preferred (see section 5.8.4). 

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists Group. Comprehensive side effect profile of anastrozole and tamoxifen as adjuvant treatment for early stage breast cancer long term safety analysis of the ATAC trial. Lancet Oncol 2006 7 633 13. 

Hot flushes/flashes remain a problem when tamoxifen is used to treat breast cancer. In a 4-week study in 22 women with this problem considerable relief was obtained by simultaneous use of oral gabapentin 300 mg tds (121). Occasional side effects were nausea, rash and excessive sleepiness. 

Andia D, Lafuente P, Matorras R, Usandizaga JM. Uterine side effects of treatment with tamoxifen. Eur J Obstet Gynecol Reprod Biol 2000 92(2) 235 10. 

Gallicchio L, Lord G, Tkaczuk K, Danton M, Lewis LM, Lim CK, Flaws JA. Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer. Breast Cancer Res Treat 2004 85 89-97. 

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