Letrozole is a specific non-steroidal aromatase inhibitor that has little or no effect on adrenal glucocorticoid or halocorticoid synthesis. Letrozole was approved in the United States in 1997 for the treatment of postmenopausal estrogen receptor-positive breast cancer.
USES:
Letrozole may be used as an adjunctive therapy for postmenopausal estrogen-sensitive breast cancer once daily (orally) for up to five years. Letrozole may also be used as a first-line treatment for postmenopausal estrogen receptor-positive (or unknown) locally advanced or metastatic breast cancer.
Related research:
Letrozole is a new generation aromatase inhibitor, which is a synthetic benzytriazole derivative. By inhibiting aromatase, letrozole can reduce estrogen level, thereby eliminating the stimulation of estrogen on tumor growth. In vitro and in vivo studies have shown that letrozole can effectively inhibit the transformation of androgen to estrogen, and estrogen in postmenopausal women mainly comes from the aromatization of androgen precursor substances in peripheral tissues, so it is especially suitable for postmenopausal breast cancer patients.The in vivo activity of Letrozole is 150-250 times stronger than that of the first generation aromatase inhibitor amlumeter. Because of its high selectivity, it does not affect glucocorticoid, salt corticosteroid and thyroid function, and has no inhibitory effect on adrenal corticosteroid secretion when used in large doses, so it has a high therapeutic index. Various preclinical studies have shown that letrozole has no potential toxicity to all systems of the body and target organs, and has good tolerance and strong pharmacological effects. Letrozole has a stronger antitumor effect than other aromatase inhibitors and antiestrogen drugs. Since 2009, the global sales volume of trazole has reached us $1.266 billion, ranking the first in this class of antitumor drugs, with a good market prospect.
hepatotoxicity
Elevated serum enzyme levels occur in 1% of patients, but are usually mild, asymptomatic, and self-limiting, requiring little dose adjustment. Long-term use of Letrozole is rarely associated with clinically significant liver injury. If it does, it usually appears within the first six months of treatment and symptoms vary. The number of relevant cases in the literature is too small to summarize clinical features. Symptoms of immune hypersensitivity (fever, rash, and eosinophilia) are uncommon, and the proportion of autoantibody synthesis is low. There are no reported cases of letrozole induced acute liver failure, chronic hepatitis or biliary disappearance syndrome. Unlike tamoxifen, letrozole does not cause fatty liver, steatohepatitis or cirrhosis.
Damage mechanism
The cause of liver injury caused by letrozole may be related to toxic or immune intermediates produced by metabolism. Letrozole is metabolized primarily by the liver cytochrome P450 system and is a potent inhibitor of CYP 2A6 and mildly inhibits CYP 2C19.
Medication outcomes and medication management
Letrozole-induced liver injury is usually mild and self-limiting, presenting as a temporary, asymptomatic elevation of serum enzymes. Other aromatase inhibitors have been reported to cause acute liver failure in women, but not letrozole. There is little evidence of cross-sensitivity between Letrozole and tamoxifen and other aromatase inhibitors (chemically very different from Letrozole) to cause liver injury.
disclaimer
It is provided as knowledge only for the reference and exchange of the industry. No guarantee is made for its accuracy and completeness. You should not use this as a substitute for your own independent judgment, and therefore you do so at your own risk.
