Fitzaekerly: Antineoplatic Hormonal Drugs Flashcards
cancers depend on this for growth
steroids
benefit of steroid dependent cancer
predict whether cancer will respond to tx (take biopsy and see if receptors are present)
Drugs that inhibit LH and FSH secretion
GnRH analogues
GnRH antagonist
Goserelin
leuprolide
GnRH analogues
how do GnRH analogues cause a flare response
mimic release of GnRH>
increase in FSH/LH>
increase in testosterone/estrogen>
FLARE (increase in cancer growth/bone pain)
long term continuous administration of GnRH analogue
increase in steady state concentrations> decrease receptor expression in pituitary> decrease in FSH/LH> decrease in estrogen/testosterone> decrease in GnRH expression
how are GnRH analogues administered
depot form
TU of Goserelin and Leuprolide
advanced prostate cancer
PRE-MW w/ ER + breast cancer
acute toxicity of GnRH analogues
flare response> bone pain
pain at injection site
*can lead to decreased hormone levels long term
Degarelix
GnRH antagonist
Why may Degarelix be preferred over a GnRH analogue?
NO flare response
FASTER decrease in testosterone levels
injection site rxn is only toxcitiy
EXPENSIVE
Dutasteride
Finasteride
5 alpha reductase inhibitors
MOA of Finasteride
inhibits converstion of testosterone to DHT> decreased cell growth
used to tx:
BPH
Male pattern baldness
prevention in prostate cancer pts w/ high PSA
Finasteride
TERATOGENCITIY
impotence
Finasteride
*may lessen decrease in bone density/muscle wasting!!
abiraterone acetate
17 alpha hydroxylase
blocks early stages of androgen syntehsis but DOES NOT INTERFERE w/ conversion of pregnenolone
17 alpha hydroylase
used to tx:
metastatic prostate cancer that is resistant to other androgen blocking regimens
abiraterone acetate
Irreversibly binds and inhibits aromatase
exemastane
first line non steroidal aromatase inhibitors
anastrozole
letrozole
3rd line non steroidal aromatase inhibiotr
aminoglutethimide
why is aminoglutethimide a third line tx?
decreases concentrations of adrenal glucocorticoids, mineralcorticoids, sex hormones
blocks the conversion of testosterone/adrostenedione to estradiol and estrone
aromatase inhibitors
which aromatase inhibotrs REVERSIBLY block the enzyme
non steroidals
1st line tx for ER+ breast cancer in POST MW
Aromatase inhibitors
ADRENAL INSUFFICIENCY toxicity
F, Nausea, rash, HA
aminoglutethamide
> ultimately leads to increase in ACTH> increase in cortisol and bone marrow suppression
POLYARTHRALGIA decreased bone density increased hot flashes Nausea HA
Anastrazole
letrozole
exemestane
Bicalutamide
flutamide
nilutamide
anti androgens
decrease binding of Test to receptor>
increase in LH/FSH>
increased production of testosterone
Bicalutamide
flutamide
nilutamide
not given ALONG or for very long because of SE and are often used w/ GnRH analogue (goserelin/leuprolide) to prevent FLARE response
Anti-androgens
androgen deprivation therapy
main stay of prostate cancer tx
NSSA + GnRH agonist
complete androgen blockade
newer anti-androgens that have decreased toxicity
bicalutamide
nilutamide
DECREASE IN SEXUAL FXN
HOT FLASHES
DECREASE IN LVIER FXN
METHENOGLOBINEAMIA
anti-androgens
MOA of anti-estrogens
compete w/ estrogen for binding to estrogen receptor
raloxifene
tamoxifen
toremifene
SERMS
partial agonists
Fulverstrant
SERD
full antagonist
these drugs will give you NO benefit after 5 yrs
are taken orally
and take 4-6 weeks to reach a steady state
SERM
given IM at 1 month internvals
and take only 7 mos to reach a steady state
SERD
which anti-estrogen is metabolized in the liver by CYP3A?
SERD
mainstay tx for ER+ cancers in POST MW
Anti-estrogens
what drugs are NOT used in PRE-MW b/c of feedback loop?
anti-estrogens
Tamoxifen is most effective in what cancers
ER+ PR+
affect of estrogen on tissues
poliferative in breast and uterus
prevents bone resorption
decrease in estrogen can lead to hot flashes, N and V
anti-estrogens
agonist in the uterus that can lead to an increase in endometrial cancer
tamoxifen
anti-androgen that can cause GI problems, HA, back pain and injection site rxns
fulverstrant
which mechanism of antineoplastic drugs is NOT used in bresat cancer therapy
differntiating agents
Cytotoxic Drug regimens for BC
FAC: Fu, Doxo, cyclophosphamide
(used until reach max dose of doxo b/c of cardiotoxicity)
CMF: cyclo, MTX, 5-FU
target ER + BC
tamoxifen, tormifene, fulverstrant
anastrazole, letrozole, exemestane
used to tx her2NEU cancers
trastuzumab
