Hormonal therapies for prostate cancer Flashcards
Prostate cancer
- most commonly diagnosed cancer in men
- second most common cause of cancer deaths in men in U.S.
- most patients diagnosed at early stages before metastatic disease
- treatment for non metastatic -
- surgery
- radiation
- pharmacologic androgen deprivation therapy (ADT)
- treatment for metastatic -
- pharmacologic ADT (aka chemical castration)
- GnRH agonist or antagonist
-metastatic cancer that failed to respond to ADT is “castration-resistant”
ADT
- androgen deprivation therapy
- this is hormonal therapy for prostate cancer
- the GOAL is to reduce concentration of testosterone in the body
- causes symptoms of HPYOGONADISM
- hot flashes,
- loss of libido/impotence
- gynecomastia
- hair thinning
- peripheral edema
- long term use causes metabolic complications: weight gain, hyperlipidemia, diabetes
associated with QT prolongation
GnRH Agonists
- gonadotropin release hormone agonist*
- luteinizing hormone releasing hormone agonists*
- reduce testosterone synthesis via negative feedback mechanism
1) cause initial surge in testosterone concentrations
2) followed by a gradual reduction in testosterone concentrations - initial surge may cause TUMOR FLARE in metastatic disease
- symptoms of TUMOR FLARE ::: bone pain, urination problems
- to PREVENT SYMPTOMS of TUMOR FLARE give antiandrogens concomitantly for several weeks with initiation of GnRH agonists
leuprolide
Lupron
Lupron Depot
GnRH agonist
- can cause TUMOR FLARE ::: start antiandrogen 1 week before 1st injection
goserelin
Zoladex
GnRH agonist
- can cause TUMOR FLARE ::: start antiandrogen 1 week before 1st injection
GnRH CLINICAL PEARLS & SIDE EFFECTS & CONTRAINDICATIONS
DOSING
^^^ given subcutaneous or IM injection monthly or less frequently^^^
^^^dose and schedule depend on formulation^^^
CLINICAL PEARLS
- leuprolide & goserelin can be used to treat breast in women*
- osteoporosis risk :: consider Ca & vit D supplementation, weight bearing exercise, DEXA screening**
SIDE EFFECTS # hot flashes # impotence # gynecomastia # peripheral edema # QT prolongation # metabolic effects (dyslipidemia, hyperglycemia)
CONTRAINDICATIONS
- pregnancy
- leuprolide :: breastfeeding, vaginal bleeding
GnRH antagonist
- does not cause an initial surge in testosterone concentrations
degarelix - Firmagon
- once monthly SQ injection -
- osteoporosis risk
- NO TUMOR FLARE
- same SIDE EFFECTS as GnRH agonists
1st GENERATION ANTIANDROGENS
- competitively inhibit the binding of testosterone to prostate cancer cells
- ONLY USED IN COMBO with GnRH agonists
- monotherapy ineffective due to an upregulation in the expression of androgen receptors
bicalutamide
Casodex: 50mg PO QD
1st GEN antiandrogen
2nd GENERATION ANTIANDROGENS
- unlike 1st GEN, does NOT cause upregulation in expression of androgen receptors and can be used as MONOTHERAPY
- enzalutamide :: Xtandi
enzalutamide
Xtandi
2nd GEN antiandrogen
160mg (4 x 40mg capsules) PO QD
-can be used as MONOTHERAPY (no upregulation of androgen receptors)
SIDE EFFECTS
- HTN
- peripheral edema
- hot flashes
- fatigue
WARNING
- seizures
CONTRAINDICATIONS
- pregnancy
- partner to use effective contraception
androgen biosynthesis inhibitor
- interferes with specific enzymes to decrease testosterone production in the testes and adrenal gland
- MUST be given with PREDNISONE to cause negative feedback on production of aldosterone & prevent symptoms of hypoaldosteronism
abiraterone
Zytiga
1000mg (4 x 250mg tabs) PO QD on empty stomach (1h before or 2h after food)
- given with prednisone 5mg PO BID
- androgen biosynthesis inhibitor
CLINICAL PEARLS
- avoid concurrent use with strong 3A4 inducers
- dose adjustment REQUIRED if concomitant strong 3A4 inducer
SIDE EFFECTS
- mineralacorticoid excess
- fluid retention
- HTN
- hypokalemia
- hepatotoxicity
- hyperglycemia
- increased triglycerides
- hypophosphatemia
- hot flashes
CONTRAINDICATIONS
pregnancy
