what are hormonal agents used for? when are they used?
only works on hormone-dependant tumors
- estrogen/progesterone dependent (ex: anti estrogens, aromatase inhibitors)
- testosterone dependent (ex: GnRH modulators, androgen antagonists, CYP17 inhibitors)
often used as adjuvant to surgery and radiation
- post-op: decrease risk of recurrence and kill some metastasized cells.
- pre-op: decrease size of tumor
- overall decrease recurrence rate and prolong life
what are 3 different classes of breast cancer agents?
estrogen receptor modulators
aromatase inhibitors
cyclin dependent kinase 4/6 inhibitors
what is the action, indication, adverse effects of Tamoxifen?
anti-estrogen drug
- blocks the action of estrogen at breast tissue + other locations -> cancer cell proliferation is prevented
breast cancer therapy
- prodrug -> CYP2D6 activation (CYP2D6 inhibitors interactions !!!)
- long half-life -> single daily dose
- recurrence decline after 5 years = 47%
breast cancer prophylaxis
- decreased breast cancer development by 44% in 4 years
- endometrial cancer development INCREASE
- appropriate only for high risk individuals
adverse effects
- endometrial cancer
- thrombosis + cardiovascular events
- menopause Sx: hot flashes, fluid retention, vaginal discharge...
- very powerful teratogen
what is the action, indication, adverse effects of anastrozole?
aromatase inhibitor
- inhibits the action of the aromatase enzyme which is responsible from for converting testosterone into estrogen
- reduce quantity of estrogen synthesis
1st choice for ER positive breast cancer in post menopausal women
- super high efficacy, so risk of osteoporosis is so high that it cannot be initiated before menopause
- no risk of endometrial cancer or cardiovascular events
adverse effects
- bone pain: use acetaminophen to manage
- bone loss: use vit D to manage
what is the action, indication, adverse effects of Palbociclib + Ribociclib?
CDK 4/6 inhibitors
- always have to be combined with letrozole (aromatase inhibitor) to be sufficiently active
reserved for types of breast cancer that are resistant to other treatments
adverse effects: SUPER toxic
- bone marrow suppression
- neutropenia
- QT prolongation
- hepatotoxicity
what is the action, indication, adverse effects of Trastuzumab?
anti-HER2 agent
- monoclonal antibody that inhibits action of HER2
- HER2 is a receptor that promotes cell growth and it is predominantly expressed on breast cancer cells
only for HER2 positive breast cancer patients
adverse effects
- cardiotoxicity: HER2 receptors are also on heart tissue
- hypersensitivity: fatal flu like syndrome that develops within 1st dose
what is the action, indication, adverse effects of Ado-Trastuzumab Emtansine?
dual mechanism of action
- trastuzumab: inhibits action of HER2
- emtansine: cytotoxic, inhibits microtubule formation
because some cancer cells become resistant to Trastuzumab by absorbing the antibodies inside and degrading it so that it was to stop inhibiting the HER2, but if you add cytotoxic agent this doesn't happen
for HER2 breast cancer patients resistant to Trastuzumab + Paclitaxel
adverse effects:
- same as Trastuzumab
- hepatotoxicity
- neurotoxicity
- teratogen
what are adjuvants?
drugs given to minimize toxicity associated with treatment, not meant to treat the cancer
- doxorubicin and cyclophosphamide or paclitaxel are very common for breast cancer
how do prostate cancer drugs work?
objective is to block testosterone production from 3 synthesis sites
- testes
- adrenal glands
- prostate tumors
physical castration only removes testes production
what is the action, indication, toxicity management of Leuprolide?
anti-testosterone agent: GnRH agonist
- initial testosterone flare up followed by chemical castration (amount increases after the admin but then quickly decreases and goes down to 0)
- only decreases testosterone production at the testes
indication
- advanced prostate carcinoma
toxicity management
- androgen receptor blocker -> minimize flare and adrenal/prostate synthesis
- zolendronate or denosumab or Vit D -> mitigate skeletal related events
what is the action, indication, toxicity management of Degarelix?
anti-testosterone agent: GnRH antagonist
- immediately inhibits testosterone levels
- no flare
- safety+efficacy same as Leuprolide
- half life = 53 days (this is HUGE)
what is the action, indication, toxicity management of Flutamide?
anti-testosterone: androgen receptor blocker
- inhibits adrenal + prostatic testosteron
- adjuvant to chemical/surgical castration
- decreased Leuprolide flare
toxicity
- same as GnRH agonists
- hepatotoxicity
- teratogen
discontinue after flare risk period
- no further advantage + increases toxicity
what is the action, indication, toxicity management of Abiraterone?
anti-testosterone: CYP17 inhibitor
- blocks de novo testosterone synthesis
- usually combined with prednisone
indication
- metastatic castration-resistant prostate cancer
- increases survival around 4 months
toxicity
- glucocorticoid deficiency
- hyperaldosteronism -> leads to hypokalemia + HTN
- hepatotoxicity -> do LFT every 2 weeks
- teratogen
- hepatic enzyme interactions -> metabolized by CYP3A4, inhibits CYP2D6
what is the action, indication, dosage, toxicity management of Sippuleucel-T?
immunotherapy agent
- unique to each patient
- moderate efficacy + high cost
- slight survival improvement over chemo
- no change in tumor progression
dosage
- 3 doses, 2 weeks apart
use
- minimally symptomatic metastatic castration resistant prostate cancer
toxicity management
- NSAIDs + anti-histamine pre-treatment to decrease infusion reactions