Hormonal Management of Cancer Flashcards
Principle behind hormonal management of breast and prostate cancer
take advantage of endocrine signaling pathways and feedback loops, to inhibit the growth and proliferation of cancer cells influenced by hormones- static agents
used as adjuvants to surgery/radiation
never used concurrently with chemo bc chemo targets ACTIVELY DIVIDING CELLS
only effective if cancer cells are ER and or PR POSITIVE
Classes of hormonal drugs primarily used as adjuvants in Tx breast cancer
SERMs
Aromastase Inhibitors
Selective Estrogen Receptor Modulators Drugs
Tamoxifen
Raloxifene
Toremifene
SERMs MOA
inhibit nuclear binding of ER, blocking stimulation of breast cancer cells
Translocates to nucleus inhibiting DNA synthesis and decreasing estrogen effects
locally-decrease secretion of TGF alpha, increase secretion of TGFbeta
SERMs MOA General
Non-steroidal estrogen agonist/antagonists
agonists in bone/endometrium
antagonists in breast tissue
Role of Tamoxifen in BC
adjuvent tx of breast cancer after surgery/radiation
pre and post menopausal women
used prophylactically in high risk women and in DCIS
Tamoxifen (SERM) Tox
Hot flashes N/V edema Thromboembolism Cataracts ENDOMETRIAL CA
Tamoxifen Drug Interactions
metabolized to more active compounds by CYP2D6
anything that inhibits 2D6 will decrease efficacy
use venlafaxine to treat hot flashes bc other SNRIs, SSRIs interact with 2D6
Raloxifene
SERM, same mechanism as Tamoxifen with less efficacy but decreased SE prolife (VTE, endometrial cancer, cataracts)
have to base decision on what to use on individual patient
only postmenopausal
Toremifene
SERM- no advantage to tamoxifen
cross-resistant with tamoxifen
post-menopausal only
same SE profile
Aromatase Inhibitors Drugs?
Anastrozole, letrozole, exemestane
Aromatase Inhibitors MOA
Inhibits aromatase and blocking conversion of androstenedione to estrone and testosterone to estradiol in peripheral tissues
markedly suppressing estrogen levels in postmenopausal women
AI indications
treat locally advanced or or metastatic bc in postmenopausal women
with disease progression following tamoxifen therapy
Start with tamoxifen and follow up with AI’s for 5 years total
AI toxicity (all similar)
fatigue arthralgias/myalgias osteopenia/osteoporosis hot flashes vaginal dryness
General treatment strategy for breast cancer in premenopausal women
- removal of primary tumor
- chemo
- tamoxifen (never WITH chemo)
- removal of ovarian estrogen production
General treatment strategy for breast cancer in postmenopausal women
- removal of primary tumor
- chemo/ or taxomifen
- AI- needs to be incorporated somehow in treatment to decrease estrogen production in the periphery
GnRH agonists?
Goserelin
Histrelin
Leuprolide
Triptorelin
GnRH agonists MOA?
Used in prostate cancer- all equivalent in efficacy and toxicity
bind receptors on AP and after initial surge, suppresses FSH, LH which decreases testosterone
internalization of GnRH receptors on AP
GnRH agonists Tox?
hot flashes Gynecomastia, breast tenderness, pain osteoporosis goserelin: HA, vaginitis, diaphoresis histrelin: urinary retention TUMOR FLARE- first week in men with prostate cancer
Anti- Androgenic Agents?
Nilutamide
Bicalutamide
Flutamide
Anti-androgen MOA?
non-steriodal anti-androgen binds to androgen receptors and comp inhibits binfing of DHT and testosteron
NOT TO BE USED ALONE
used in combo with GnRH agonists for prostate cancer to prevent tumor flare
Anti-androgen tox?
gynecomastia hot flashes increased liver enzymes N/V Diarrhea- Flutamide Disulfuram like- Nilutamide
abiraterone MOA
selectively and irreversibly inhibits CYP17, inhibiting formation of testosterone precursors
neeed to dose with prednisone bc also cutting out cortisol
abiraterone tox
edema
hypertrigylceride
hypokalemia, hypophosphatemia
diarrhea
enzalutamide MOA
approved for treatment of metastatic castration resistant PC in patients previously treated with docetaxel
pure androgen receptor signaling inhibitor, ultimately leading to apoptosis
enzalutamide tox
peripheral edema fatigue headache hot flashes diarrhea neutopenia
fulvestrant use
second line in post-menopausal women after cancer progression on SERM of AI
fulvestrant MOA
steroid compound competatively binds estrogen receptors, forms complex causing down regulation of ER’s
pure antagonist
fulvestrant tox
hot flashes nausea angioedema weakness local site reaction
Degarelix MOA
LHRH antagonist equiv to leuprolide in decreasing testosterone, advantage is immediate down regulation of testosterone without tumor flare
Degarelix tox
hot flashes
injection site rxn
limited to painful enlargement of prostate
Combined Androgen Blockade (CAB)
use of LHRH agonist with anti-androgenic- impt for preventing tumor flare
