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USU Pharm lec 73

Cancer Chemotherapy IV (hormonal agents)

QuestionAnswer
tamoxifen (SERM). mech competitive inhibitor at estrogen receptor. BREAST TISSUE: antagonistic effect, ENDOMETRIAL TISSUE: agonistic effect. Much longer half life, but lower receptor affinity than estradiol. Reduces breast cancer recurrence by 30%.
raloxifene (SERM). mech and tox as effective as tamoxifen in prevention, and has lower rates of uterine cancer, fewer blood clots, fewer side effects (side effects are the same as tam, but all are reduced)
fulvestrant. mech, administration, indication pure estrogen receptor ANTAGONIST. given i.m. injection. for people on tamoxifen who's cancer is still progressing
anastrozole. mech, tox selective and irreversible inhibitor of aromatase. anastrozole is at least as effective as tamoxifen, and better tolerated! NO risk of endometrial cancer or thromboembolic events. USE BEYOND 5 YEARS. FIRST-LINE as an alternative to tamoxifen. VERY EFF
letrozole. mech, tox selective and irreversible inhibitor of aromatase. NO risk of endometrial cancer or thromboembolic events. USE BEYOND 5 YEARS. FIRST-LINE as an alternative to tamoxifen. VERY EFFECTIVE
exemestane. mech, tox selective and irreversible inhibitor of aromatase. NO risk of endometrial cancer or thromboembolic events. USE BEYOND 5 YEARS. FIRST-LINE as an alternative to tamoxifen. VERY EFFECTIVE
transtuzumab. mech, tox humanized monoclonal antibody against HER2/erbB-2 receptor to treat advanced breast cancers expressing that receptor. Tox: cardiomyopathy (esp. when combined with anthracyclines "rubicins")
lapatinib. mech, combine with what? for advanced breast cancers expressing HER-2 that don't respond to trastuzumab. It's a tyrosine kinase inhibitor targeting both EGFR and Her2/neu. Great to combine with chemotherapy.
leuprolide. mech GnRH AGONIST. Initial FSH and LH "flare" but then GnRH receptors become desensitized, and estradiol/progesterone drop off the face of the earth.
geserelin. mech GnRH AGONIST. Initial FSH and LH "flare" but then GnRH receptors become desensitized, and estradiol/progesterone drop off the face of the earth.
abarelix. mech GnRH antagonist, inhibits LH and FSH release, and inhibits testosterone production. NO FLARE.
flutamide. mech, use, tox prevents endogenous androgens binding to androgen receptors (for "flares" by leuprolide and goserelin). used for metastatic prostate cancer when unresponsive to androgen ablation therapy. Tox: diarrhea (most common), gynecomastia, hepatotoxicity (rare)
bicalutamide. mech, use, tox non-steroidal antiandrogen. more effective in prostate cancer treatment than flutamide. LESS side-effects. for "flare" caused by leuprolide and goserelin.
tamoxifen. who do you use it on, and for how long? Best in post-menopausal women with ER+ breast cancer. use up to 5 years ONLY (becomes partial agonist in breast after 5 years). Also use in HIGH RISK pts as prophylaxis (reduces risk by 45%)
tamoxifen. adverse reactions hot flashes, nausea, vomiting, vaginal bleeding. Endometrial carcinoma (it's an agonist there!), Thromboembolic events (Estrogen agonists decrease antithrombin III). NEVER give fluoxetine with tamoxifen (flu inhibits CYP2D6) which is what metabolizes tam
tamoxifen. benefits reduces total cholesterol, preserves bone density
GnRH agonists (leuprolide, goserelin). use and tox Used in metastatic breast cancer in pre-menopausal women. MAIN use is for prostate cancer. hot flashes sweating and nausea form decreased sex hormones
how do you treat Estrogen Receptor negative pts? chemotherapy (both pre and post-menopausal). ONLY treat with chemo if high risk.
how do you treat "low risk" ER positive premenopausal women? tamoxifen or relaxifene
how do you treat "intermediate and high risk" ER positive premenopausal women? Chemo, tamoxifen/raloxifene, and GnRH agonists (GnRH agonists would serve no purpose in post-menopausal women)
how do you treat "intermediate and high risk" ER positive post-menopausal women? low risk: tamox/ralox or aromatase inhibitor. Intermediate/high risk: tamox/ralox or aromatase inhibitor with chemo.
Created by: iplayguitar
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