Hormonal Management of Cancer

Question 1

Principle behind hormonal management of breast and prostate cancer

Answer 1

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

Question 2

Classes of hormonal drugs primarily used as adjuvants in Tx breast cancer

Answer 2

SERMs

Aromastase Inhibitors

Question 3

Selective Estrogen Receptor Modulators Drugs

Answer 3

Tamoxifen
Raloxifene
Toremifene

Question 4

SERMs MOA

Answer 4

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

Question 5

SERMs MOA General

Answer 5

Non-steroidal estrogen agonist/antagonists
agonists in bone/endometrium
antagonists in breast tissue

Question 6

Role of Tamoxifen in BC

Answer 6

adjuvent tx of breast cancer after surgery/radiation
pre and post menopausal women
used prophylactically in high risk women and in DCIS

Question 7

Tamoxifen (SERM) Tox

Answer 7

Hot flashes
N/V
edema
Thromboembolism
Cataracts
ENDOMETRIAL CA

Question 8

Tamoxifen Drug Interactions

Answer 8

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

Question 9

Raloxifene

Answer 9

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

Question 10

Toremifene

Answer 10

SERM- no advantage to tamoxifen
cross-resistant with tamoxifen
post-menopausal only
same SE profile

Question 11

Aromatase Inhibitors Drugs?

Answer 11

Anastrozole, letrozole, exemestane

Question 12

Aromatase Inhibitors MOA

Answer 12

Inhibits aromatase and blocking conversion of androstenedione to estrone and testosterone to estradiol in peripheral tissues
markedly suppressing estrogen levels in postmenopausal women

Question 13

AI indications

Answer 13

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

Question 14

AI toxicity (all similar)

Answer 14

fatigue
arthralgias/myalgias
osteopenia/osteoporosis
hot flashes
vaginal dryness

Question 15

General treatment strategy for breast cancer in premenopausal women

Answer 15

1. removal of primary tumor
2. chemo
3. tamoxifen (never WITH chemo)
4. removal of ovarian estrogen production

Question 16

General treatment strategy for breast cancer in postmenopausal women

Answer 16

1. removal of primary tumor
2. chemo/ or taxomifen
3. AI- needs to be incorporated somehow in treatment to decrease estrogen production in the periphery

Question 17

GnRH agonists?

Answer 17

Goserelin
Histrelin
Leuprolide
Triptorelin

Question 18

GnRH agonists MOA?

Answer 18

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

Question 19

GnRH agonists Tox?

Answer 19

hot flashes
Gynecomastia, breast tenderness, pain
osteoporosis
goserelin: HA, vaginitis, diaphoresis
histrelin: urinary retention
TUMOR FLARE- first week in men with prostate cancer

Question 20

Anti- Androgenic Agents?

Answer 20

Nilutamide
Bicalutamide
Flutamide

Question 21

Anti-androgen MOA?

Answer 21

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

Question 22

Anti-androgen tox?

Answer 22

gynecomastia
hot flashes
increased liver enzymes
N/V
Diarrhea- Flutamide
Disulfuram like- Nilutamide

Question 23

abiraterone MOA

Answer 23

selectively and irreversibly inhibits CYP17, inhibiting formation of testosterone precursors
neeed to dose with prednisone bc also cutting out cortisol

Question 24

abiraterone tox

Answer 24

edema
hypertrigylceride
hypokalemia, hypophosphatemia
diarrhea

Question 25

enzalutamide MOA

Answer 25

approved for treatment of metastatic castration resistant PC in patients previously treated with docetaxel
pure androgen receptor signaling inhibitor, ultimately leading to apoptosis

Question 26

enzalutamide tox

Answer 26

peripheral edema
fatigue
headache
hot flashes
diarrhea
neutopenia

Question 27

fulvestrant use

Answer 27

second line in post-menopausal women after cancer progression on SERM of AI

Question 28

fulvestrant MOA

Answer 28

steroid compound competatively binds estrogen receptors, forms complex causing down regulation of ER’s
pure antagonist

Question 29

fulvestrant tox

Answer 29

hot flashes
nausea
angioedema
weakness
local site reaction

Question 30

Degarelix MOA

Answer 30

LHRH antagonist equiv to leuprolide in decreasing testosterone, advantage is immediate down regulation of testosterone without tumor flare

Question 31

Degarelix tox

Answer 31

hot flashes
injection site rxn
limited to painful enlargement of prostate

Question 32

Combined Androgen Blockade (CAB)

Answer 32

use of LHRH agonist with anti-androgenic- impt for preventing tumor flare