Thanks
for
Visiting
|
|
| |
|
| |
Treatment of Breast Cancer - C.)Aromatase inhibitor
|
|
Aromatase inhibitor is the enzyme that inhibits the conversion of androgens to estrogens. Besides, it will reduce estrogen production in postmenopausal women who produce estrogen mainly from androstenedione and testosterone in many tissues such as adipose tissue, skin, muscle and liver. Aromatase is also present in the cells of two-thirds of breast carcinomas and many breast cancers are estrogen dependent. Below are the drugs that is aromatase inhibitor :
- Anastrozole
- Letrozole
- Exemestane
- Formestane
- Aminoglutethimide
- Vorozole
Anastrozole (Arimidex®)
 1. Therapeutic use
Anastrozole is a potent and selective nonsteroidal inhibitor of the aromatase (oestrogen synthetase) system and for the treatment of advanced or locally advanced breast cancer and as adjuvant treatment in early breast cancer, in postmenopausal women in a dose of 1 mg daily by mouth and not for oestrogen receptor-negative disease.
2. Side effect
The most frequent adverse effect that patients might experience are that patient will fell no appetite to eat, feel nauseated, vomit and diarrhoea; loss of strength; hot flushes; dizziness and drowsiness; headache and rash. They might also get hair thinning, vaginal dryness or bleeding, oedema, dyspnoea, myalgia and arthralgia, bone fractures, fever, weight gain, leucopenia and a flu-like syndrome. Less patients are reported that have abnormalities in liver enzyme value, thromboembolism and increases in total cholesterol and very rare cases of erythema multiforme and Stevens-Johnson syndrome have occurred.
Besides that, reductions in bone mineral density may occur. For example, patients with or at risk of osteoporosis should therefore have their bone density assessed at the start of therapy and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis should be started as appropriate and carefully monitored. It is contraindicated in premenopausal women(particulary in prengnacy). Furthermore, this drug have the effects on the musculoskeletal system. Arthralgia occurs in 10-15% of patients treated eith anastrozole, possibly as a result of the very low oestrogen concentrations achieved.
3. Contradication
Food decreases the rate of absorption.
For more information, click here.
Letrozole (Femera®)
1. Therapeutic use
Letrozole is a selective nonsteroidal inhibitor of the aromatase (estrogen synthetase) system and for the treatment of advanced or locally advanced breast cancer in postmenopausal women. Letrozole given as neoadjuvant (preoperative) therapy to those with localized hormone-receptor positive disease, to allow subsequent breast-conserving surgery. Besides that, used for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer; treatment is generally given for 5 years, although optimal duration of therapy is unknown. Furthermore, used as extended adjuvant therapy, treatment should continue for 3 years or until tumour relapse occur. The usual dose is 2.5 mg daily by mouth.
2. Side effect
Letrozole has the adverse effect like Anastrozole. But it also has effects on the skins - toxic epidermal necrolysis. Letrozole has the interaction with tamoxifen.
For more information, click here.
Exemestane (Aromasin®)
 1. Therapeutic use
Exemestane is a selective inhibitor of the aromatase (oestrogen synthetase)system. Exemestane used in the treatment of advanced breast cancer, in postmenopausal women who are no longer responsive to anti-estrogen therapy. And it is used for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer, after 2-3 years of initial adjuvant tamoxifen treatment; a total of 5 years of adjuvant hormonal therapy should be given. The recommended dose is 25 mg once daily by mouth, preferably after a meal. In patients receiving potent inducers of the cytochrome P450 isoenzyme CYP3A4 (rifampicin or phenytoin), the recommended dose of exemestane is 50 mg once daily by mouth.
2. Side effect
The frequent adverse effects are gastrointestinal disturbances, hot flashes, arthralgia, myalgia, sweating, fatigue and dizziness and rare in headache, insomnia somnolence, depression, skin rashes, alopecia, asthenia and peripheral and leg aedema. Occasionally thrombocytopenia and leucopenia. The reductions in bone mineral density can occur with long term used. Density should therefore be assessed at the start therapy, in those with osteoporosis or at risk of it and patients monitored during therapy. Exemestane is contraindicated in premenopausal women (particularly in pregnancy).
3. Contraindication
Exemestane is interact with rifampicin (a potent inducer of CYP isoenzymes) and estrogen containing drugs as these would negate its pharmacological action.
For more information, click here.
Formestane (Lentaront®)
 1. Therapeutic use
Formestane is an inhibitor of the aromatase (oestrogen sythethase) system which is responsible for the production of estrogens from androgens and used for its anti-oestrogenic properties in the endocrine treatment of advanced breast cancer in postmenopausal women. Formestane is given by intramuscular injection, as an aqueous suspension, in doses of 250 mg every 2 weeks and should be given into each buttock alternately.
2. Side effect
Adverse effects are local irritation and pain at the site of injection and hot flushes due to estrogen deprivation. Occasionally/ rarely rashes and pruritus, alopecia or hypertrichosis, drowsiness, dizziness, emotional lability, oedema of the leg, thrombophlebitis, vaginal spotting or bleeding, gastrointestinal disturbances, pelvic or muscle cramps, arthralgia, exacerbation of bone pain and a vasovagal reaction. Hypersensitivity reactions to the drug or the formulation have occurred. Care should be taken to avoid intravascular injection. Injection into or near the sciatic nerve may result in pain and nerve trauma. Caution is required if patients drive or operate machinery. Formestane has the effect on carbohydrate metabolism. Recurrent hypoglycaemic episodes developed in a diabetic patient previously well maintained on gliclazide after addition of formestane to treatment for metastatic breast cancer.
For more information, click here.
Aminoglutethimide (Orimetent)
1. Therapeutic use
Aminoglutethimide is an analogue of glutethimide and was formerly used for its weak antoconvulsant properties. It blocks the production of adrenal steroids and acts as an aromatase inhibitor to block the conversion of androgens to estrogens. Aminoglutethimide used in the treatment of metastatic breast cancer in postmenopausal or oophorectomised women and as palliative treatment in men with advanced prostatic cancer and used in treatment of Cushing’s syndrome. Usual doses range from 1 to 2 g daily by mouth, in divided doses.
2. Side effect
The most frequent as verse effects are drowsiness, lethargy and skin rashes (sometimes with fever); these generally diminish after the first 6 weeks of therapy. Dizziness and nausea occasionally occur. Leucopenia, thrombocytopenia, agranulocytosis or severe pancytopenia have occur rarely. Adrenal insufficiency may rarely occur and other endocrine disturbances including hypothyroidism and virilisation. Other rare effects include ataxia, headache, depression, gastrointestinal disturbances, hypercholesterolaemia and orthostastic hypotension. Overdosage may lead to CNS depression and impairment of consciousness, electrolyte disturbances and respiratory depression. It has effect on the liver – cholestatic jaundice accompanied by rash and fever and probably due to an idiosyncratic hypersensitivity reaction and lupus – SLE occurred.
Aminoglutethimide act as inhibit adrenal steroid production so supplementary glucocorticoid therapy with hydrocortisone must normally given, although supplementation may not be necessary in patients with Cushing’s syndrome. Some patients required mineralocorticoid. Aminoglutethimide should temporarily withdrawn in patients who undergo shock and trauma or develop intercurrent infection. The most important are blood pressure, blood counts and serum electrolytes should be regularly monitored and periodic monitoring of liver and thyroid function is recommended. Aminoglutethimide should not be given during pregnancy as pseudohermaphroditism may occur in the fetus because frequently causes drowsiness: patients so affected should not drive or operate machinery and associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
3. Contraindication
Aminoglutethimide increase rate of metabolism of some drugs. Patients also taking warfarin or other coumarin anticoagulants, theophylline, tamoxifen, medroxyprogesterone or oral hypoglycaemics, may require increased dosages of these drugs. The metabolism of dexamethasone is also accelerated, which limits its value for corticosteroid supplementation in patients receiving aminoglutethimide. If Aminoglutethimide use with diuretics may lead to hyponatraemia, while alcohol may potentiate the central effects of aminoglutethimide.
For more information, click here.
Vorozole
6. Vorozole is a selective nonsteroidal inhibitor of the aromatase system and investigated in the treatment of breast cancer.
|
|
Today, there have been 18 visitors (19 hits) on this page!
|
|
|
