Breast & Endometrial Cancer Flashcards
MOA of Aromatase Inhibitors
Aromatase; Blocks production of estrone & estradiol
Aromatase Inhibitors (3)
Anastrozole, Exemestane, Letrozole
Aromatase Inhibitor Tox
Hot flashes; nausea; hair thinning; NO effect on adrenal steroids, thyroid, or other hormones; More arthralgia & diarrhea than tamoxifen but fewer gynecologic symptoms
Aromatase Inhibitors Metabolism
Hepatic
SERMs (3)
Raloxifene, Tamoxifen, Toremifene
Raloxifene MOA
SERM; ER agonist/antagonist-estrogen effect on bone & anti-estrogen effect on mammary tissue
Tamoxifen MOA
SERM; ER agonist/antagonist-estrogen effect on bone & anti-estrogen effect on mammary tissue
Toremifene MOA
SERM; Tamoxifen derivative w/ anti-estrogenic properties
Raloxifene Tox & BBW
Increased bone mineral density; Decreases serum cholesterol, LDL, & lipoproteins; Increases apolipoprotein-A1; Retinal degeneration at high doses
BBW= Thromboembolic Dz (DVT/PE) & Stroke
Raloxifene Admin
Monthly IM
SERMs & Pregnancy?
No, teratogens
Tamoxifen Tox & BBW
Increased bone mineral density; Decreases serum cholesterol, LDL, & lipoproteins; Increases apolipoprotein-A1; Retinal degeneration at high doses
BBW= Endometrial Hypertrophy, vaginal bleeding, endometrial cancer, thromboembolic dz (DVT/PE), stroke
Tamoxifen Admin
Daily PO
Toremifene Tox & BBW
Similar AE’s to tamoxifen; Avoid w/ Hx of endometrial cancer/hyperplasia & thromboembolic dz
BBW= QT Prolongation (avoid in pre-existing conditions);
Toremifene Admin
Daily PO
Toremifene DDI
Avoid w/ CYP3A4 inhibitors
SERD (1)
Fulvestrant
Fulvestrant MOA
SERD; Pure antagonist, no estrogenic effects; Bulky substituent prevents dimerization of ER’s in nucleus=sustained downregulation of ER expression
Fulvestrant Tox
Postmenopausal symptoms: nausea, asthenia, pain, vasodilation (hot flashes), and h/a
Fulvestrnat PK
Hepatic metabolism; monthly IM-sustained plasma levels
Fulvestrnat use
Tx for ER+ metastatic BC in PM women w/ dz progression following anti-estrogen therapy
Trastuzumab MOA
HER2/neu Antibody; Binds to the juxtaglomerular region of the extracellular domain of HER2
Trastuzumab Tox
Caution- HSR w/ initial dose; Common=GI upset, asthenia, blood dyscrasias, fatigue, peripheral edema, rash, wt gain, dizziness, URTIs, pharyngitis; Rare= cardiomyopathy & HF, renal failure, hepatotox, pneumonia, respiratory failure; BBWs
Trastuzumab BBW
BBWs=Cardiomyopathy, Infusion Rxns, Pregnancy, Respiratory Distress Syndrome, Respiratory Insufficiency
Lapatinib MOA
TKI
Lapatinib Tox
Common= GI tox, anemia, thrombocytopenia, hand-foot syndrome, rash pain, h/a, backache; Serious= interstitial lung dz/pneumonitis, QT prolongation
Lapatinib PK
Extensive hepatic metabolism- 3A4 + 3A5
Lapatinib DDI
CI’d w/ concurrent use of drugs that have AE’s associated w/ pulmonary tox & QT prolongation
Lapatinib BBW
BBW=Liver Dz (b/c will lead to increased drug levels)- LFT monitoring required
Everolimus MOA
mTOR Inhibitor; Prevents cell proliferation & survival
Everolimus Tox & BBW
Non-infectious pneumonitis (sometimes fatal); Blood dyscrasias, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elev creatinine, elev liver enzymes; N/V, diarrhea, pain, constipation
Also BBW - opportunistic infections & neoplasia
Everolimus PK
3A4 & Pgp substrate; Inhibits 3A4, 2D6, & Pgp
What should you monitor when a patient is on everolimus
Monitor: blood glucose, CBC w/ differential, LFTs, serum bilirubin-creatinine-lipid profile- phosphate-triglyceride
Everolimus use
Tx in combo w/ Exemestane for advanced ER+/HER2- tumors
Which AI is steroidal, which non-steroidal?
Steroidal - exemestane
non-steroidal - letrozole, anastrazole
Non steroidal AI is reversible or irreversible?
reversible inhibitor
Steroidal AI is reversible or irreversible?
irreversible
Which drugs are given in combo with a taxane?
Pertuzumab & Trastuzumab
