Week 7 - Chapter 103 Anticancer Drugs II Flashcards
Antiestrogens
Antiestrogens are drugs that block ERs, and hence only work against cells that are ER positive. Benefits derive from depriving tumor cells of the growth-promoting influence of estrogen. Three antiestrogens—tamoxifen, toremifene, and fulvestrant—are approved for adjuvant treatment. Of these, tamoxifen is by far the most widely used.
Tamoxifen - use
Used for established breast cancer disease and for reducing occurrence in high-risk patients
Adjuvant therapy after surgery
Treatment of metastatic disease
Aromatase Inhibitors
The aromatase inhibitors are used to treat ER-positive breast cancer in postmenopausal women. These drugs block the production of estrogen from androgenic precursors, and thereby deprive breast cancer cells of the estrogen they need for growth. Aromatase inhibitors do not block production of estrogen by the ovaries, and hence are of little benefit in premenopausal women. In fact, aromatase inhibitors may cause a compensatory rise in estradiol in premenopausal patients. Aromatase inhibitors are more effective than tamoxifen and have a different toxicity profile. Unlike tamoxifen, aromatase inhibitors pose no risk of endometrial cancer and only rarely cause thromboembolism. However, they can increase the risk of fractures and have been associated with moderate to severe myalgias.
Anastrozole - use
Used to treat ER-positive breast cancer in postmenopausal women
Localized Prostate Cancer
Surgery + Radiation. (Optional Drug Treatment)
Metastatic Prostate Cancer
Drug Treatment, Castration
Androgen Deprivation Therapy
Lowers testosterone production
Drugs used to block testosterone receptors
Slows progression, increases comfort
Gonadotropin Releasing Hormone Agonists
Gonadotropin Releasing Hormone Antagonists
Gonadotropin-Releasing Hormone Agonists
The gonadotropin-releasing hormone (GnRH) agonists suppress production of androgens by the testes—but not by the adrenal glands and prostate cancer cells. Currently, four GnRH agonists are available: leuprolide, triptorelin, goserelin, and histrelin. All four are indicated for cancer of the prostate. In addition, leuprolide is used for endometriosis
Leuprolide - use
Advanced prostate cancer
Palliation, not cure, is primary benefit
Gonadotropin-Releasing Hormone Antagonists
Like the GnRH agonists, the GnRH antagonists suppress production of androgens by the testes. However, in contrast to the GnRH agonists, the GnRH antagonists do not produce an initial tumor flare. Currently, only one GnRH antagonist—degarelix—is available.
Degarelix - use
palliative therapy of advanced prostate cancer in men who are not candidates for a GnRH agonist, and who do not want surgical castration
Suppress production of androgens
Do not produce initial tumor “flare”
Leuprolide - mechanism of action
Stimulates pituitary to release ICSH (TestisAndrogens). After initial surge, pituitary becomes desensized to stimulationreduced ICSH
Cotreatment with an androgen receptor blocker
Prevents surge effects
Blocks androgens produced by other sources
Leuprolide - adverse effects
Generally well tolerated
Hot flashes
Testosterone loss may aggravate bone pain and urinary obstruction
Concurrent treatment with androgen receptor blocker can minimize these effects
Degarelix - mechanism of action
blockade of GnRH receptors in the anterior pituitary, which decreases release of luteinizing hormone and follicle-stimulating hormone, which in turn deprives the testes of the stimulus they need for testosterone production.
Degarelix - adverse reactions
hot flashes, reduced libido, erectile dysfunction, gynecomastia, decreased muscle mass, decreased bone mass with associated increased risk of fractures and injection site reactions.
