CRITICAL FACTS VII: Drugs that interfere with hormone function
(if med school is a Minnesota forest with millions of trees,
these are the red pines)
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When used in prostate or breast cancer treatment, GnRH analogues (GOSERELIN, LEUPROLIDE) are given in “depot” form, because continuous (non-pulsatile) administration ultimately results in inhibition of LH and FSH secretion, which (in turn) reduces levels of testosterone or estrogen.
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Aromatase inhibitors target the conversion of testosterone and androstenedione to estradiol and estrone, respectively. Steroid analogues, such as EXEMESTANE, IRREVERSIBLY inhibit aromatase, while non-steroidal drugs (AMINOGLUTETHIMIDE, ANASTROZOLE and LETROZOLE) compete REVERSIBLY for the androstenedione binding site. AMINOGLUTETHIMIDE also blocks conversion of cholesterol to pregnenolone, decreasing concentrations of adrenal gluco- and mineralocorticoids as well as sex hormones.
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Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, and is usually induced medically by administration of GnRH analogues such as GOSERELIN or LEUPROLIDE. Non-steroidal anti-androgens (NSAAs; i.e., the ”LUTAMIDES”) are typically given short term, in order to prevent the “flare” response observed when GnRH agonists are first given to prostate cancer patients. This drug combination (NSAA + GnRH agonist) results in complete androgen blockade (CAB).
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TAMOXIFEN and TOREMIFENE are competitive antagonists of estrogen in the breast i.e., they are SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMs). FULVESTRANT is a newer, competitive ER inhibitor with no known agonist properties in any tissue, i.e., it is a SELECTIVE ESTROGEN RECEPTOR DOWNREGULATOR (SERD).
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Reprise from hematopoiesis! Antineoplastic agents are almost always given in combination. Correct selection of drugs in a regimen can result in decreased development of resistance, synergistic effects and decreased toxic effects. Other common chemotherapeutic strategies include pulse and rescue therapy, recruitment and synchrony.
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Breast cancer treatment is an excellent example of successful postsurgical adjuvant chemotherapy. Even in patients with metastatic disease, combination chemotherapy has been found to induce remissions in up to 50-80% of patients, with anthracycline-containing regimens now considered to be the standard of care.