Immune altering and hormonal therapy - 23 to 33 Flashcards
How does hormonal therapy work in cancer?
Steroid hormones bind steroid responsiveness element on DNA
Binding activates or promotes gene expression, usually growth factors
Hormone-response elements remain so that in presence of hormone, oncogenes can drive tumor growth
How do glucocorticoids work in cancer?
Suppress white blood cells, used in acute lymphoblastic leukemias to decrease leukemic cells
How do anti-estrogens work in cancer?
Used in breast, uterine, cervix, ovaries
How do anti-androgens work in cancer?
Used in testicular and prostate cancers
What is Tamoxifen?
Estrogen partial agonist (SERM), competes with estrogen for receptor binding
Indications for Tamoxifen?
Estrogen dependent breast tumors
Also used to reduce risk of developing breast tumors in women with strong family history, premenopausal women given for 5 years, postmenopausal 2 years
Tamoxifen toxicities
Hot flashes, nausea, vomiting, myelosuppression, pulmonary embolism
Linked to endometrial cancer and blood clots
Positive estrogenic effects on bone and cholesterol tho!
What is Toremifene?
Tamoxifen analog
Increases TNFB to decrease cell proliferation/decrease cell growth
Indication for Toremifene?
Estrogen dependent breast cancer
Looking at prostate cancer prophylaxis
Tamoxifen toxicities?
Similar response/adverse effects to tamoxifen
Hot flashes, nausea, vomiting, myelosuppression, pulmonary embolism
Linked to endometrial cancer and blood clots
Positive estrogenic effects on bone and cholesterol tho!
What is Raloxifene?
Selective estrogen receptor modulator (SERM’s)
Estrogen effect in bone, CV system
Antagonist in Breast, uterine tissue
Indication for Raloxifene
Mostly used in osteoporosis
FDA approved to reduce breast cancer risk in postmenopausal women with osteoporosis and postmenopausal at high risk for breast cancer
Raloxifene toxicities?
Increased incidence of thromboembolism, hot flashes, muscle cramps, teratogenic in animals
What is Fulvestrant?
Selective estrogen receptor down regulator (SERD’s)
Pure anti-estrogen, down regulates estrogen receptor
How is Fulvestrant administered?
Monthly IM injection
Fulvestrant indications?
Postmenopausal hormone sensitive metastatic breast cancer
Toxicities associated with Fulvestrant?
Nausea Asthenia Pain Vasodilation Headache
What is Anastrazole, Letrozole?
Nonsteroidal competitive aromatase inhibitors (decrease 98.1% of estrogen)
How are anastrazole, letrozole administered?
Oral
Indications for anastrazole, letrozole?
All women with postmenopausal estrogen sensitive breast cancer should receive aromatase inhibitors
Anastrazole, letrozole toxicities?
Nausea, hot flashes, hair thinning, muscle pain, less CV events than tamoxifen
What is Exemestane?
Irreversible steroidal aromatase suicide inhibitor (reduces estrogen by 98%)
Indications for Exemestane?
Used in postmenopausal ER + breast cancer in women after 2-3 years of Tamoxifen, or for 5 years by itself
Toxicities with Exemestane?
Nausea Hot flashes Edema Fatigue Less frequent gynecological symptoms More common visual disturbances and bone fractures
What are flutamide, nilutamide, and bicalutamide?
Synthetic nonsteiroidal anti androgens
Indications for flutamide, nilutamide, and bicalutamide
Prostate cancer
MOA for flutamide, nilutamide, and bicalutamide?
Bind androgen receptor to block testosterone stimulation of cancer cells, usually given with Leuprolide or goserelin
Toxicities with flutamide, nilutamide, and bicalutamide?
Gynecomastia
GI distress
Decreased libido
Vasomotor flushing
What are Leuprolide, Goserelin, Histrelin, Triptorelin?
Analogs of GnRH
They occupy LHRH receptor in pituitary continuously, desensitize and inhibit release of FSH and LH
FSH and LH are responsible for testosterone release
How are Leuprolide, Goserelin, Histrelin, Triptorelin administered?
Daily SubQ or monthly depot
Toxicities of Leuprolide, Goserelin, Histrelin, Triptorelin?
Impotence Hot flashes Gynecomastia Nausea Vomiting
What is Nafarelin?
Nasal spray formulation of the GnRH analogs
