2015 Antineoplastics

Critical Facts IconCRITICAL FACTS VII: Drugs that interfere with hormone function
(if med school is a Minnesota forest with millions of trees,
these are the red pines)

  1. 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.

  2. 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.

  3. 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).

  4. 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).

  5. 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.

  6. 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.

Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM