Flashcards
Breast Cancer Drugs and MOA
Cards in this deck (54)
- 1Anthracyclines drugs are1. doxorubicin***
2. daunorubicin
3. epirubicin (epidoxorubicin) ***
*** are the commonly mentioned. - 2Describe "steal liposomal"1. Use in doxorubicin (Doxil) drug delivery
2. synthetically prepared vesicle consisting of a lipid bilayer which encapsulates a drug.
3.Has lipid bilayer consisting of fully hydrogenated soy phosphatidylcholine (HSPC), encapsulates doxorubucin.
4. MPEG-DSPE, a pegylated diacylglycerol derivative, coats the bilayer, decreasing uptake by phagocytes and increasing the circulatory half-life of Doxil. - 3merit of "steal liposomal"1. Decreases AEs like cardiotoxicity compare to traditional doxorubicin solution.
2. Anthracyclines are well known for causing cardiotoxicity. - 4Anthracyclines SEs + solutions (1)1. arrhythmias and ST- and T-wave alterations.
2. permanent cardiac damage presenting
as heart failure that does not respond to HF therapy.
3. Solutions: stick w/ lifetime doses of Anthracyclines. - 5Lifetime doses of Anthracyclines. 1. Doxorubicin: -----? 2. Daunorubicin: -----? 3. Epirubicin: -------?Doxorubicin: 550 mg/m2
Daunorubicin: 1000 mg/m2
Epirubicin: 900 mg/m2 - 6Anthracyclines SEs + solutions (2)1. myelosuppression = is the dose-limiting toxicity
2. mucositis
3. emesis
4. diarrhea
5. alopecia - 7Treatment for anthracycline IV extravasates are .....1. Dimethyl sulfoxide (DMSO) 99%
2. Dexrazoxane (Totect®) - 8What is the difference btw 1. Dexrazoxane (Zinecard®) 2. Dexrazoxane (Totect®)1. Dexrazoxane (Zinecard®) = provides protection against cardiotoxicity
2. Dexrazoxane (Totect®) = for the treatment of extravasation of IV anthracycline therapy. - 9Alkylating Agent isCyclophosphamide
(a nitrogen mustard alkylating agent) - 10Cyclophosphamide is closely related to ----?ifosfamide
- 11cyclophosphamide requires activation by CYP450 to have an anticancer effect, the primary isoforms are -----?1. CYP2B6
2. some CYP3A4 - 12What is the name of the metabolite formed by cyclophosphamide wh/ causes hemorrhagic cystitis?Acrolein
- 13The therapeutic, DNA reactive metabolite is of cyclophosphamide is ----?a nitrogen mustard
- 14acrolein is a ------?bladder-toxic metabolite formed as a
result of this activation - 151. Due to bladder toxicity, -------- is necessary with either IV or PO administration of cyclophosphamide. 2. During high-dose treatment, patients should receive vigorous IV -------?1. hydration
2. hydration - 16AEs of cyclophosphamides1. Alopecia
2. Emesis (dose-dependent)
3. Hemorrhagic cystitis ***
4. Infertility issues
5. Leukopenia (dose-limiting)***
6. Secondary malignancy
7. SIADH *** - 17Taxanes drugs are ----1. Paclitaxel +/- Bevacizumab
2. Docetaxel - 18Taxanes MOA1. Inhibits microtubules disassemblage
- 19Why do patients receive dexamethasone with docetaxel?.
- 20What are the major toxicities associated with paclitaxel and docetaxel?.
- 21Why do patients receive premedication with dexamethasone, diphenhydramine and an H2 antagonist prior to paclitaxel?.
- 22Microtubule inhibitors are1. Vinorelbine
2. Eribulin
3. Ixabepilone (taxane & anthracycline failures)*** - 23Microtubule inhibitors MOA1. binds to tubulin and inhibits microtubulin formation.
2. Inhibits the formation of mitotic spindle.
3. M phase specific microtubule stabilizing agents. - 24Ixabepilone (epithilone) is associated with -----?1. myelosuppression (neutropenia)
2. peripheral neuropathy
3. cognitive impairment. - 25Ixabepilone BBW includes ------?1. a black box warning against its use in patients with impaired liver function, as this increases the risk of life threatening neutropenia.
- 26Cremophor (also used as an excipient in taxane formulations) is known to be a --------- and may lead to ----------- which can be life threatening if not treated appropriately1. sensitizing agent
2. hypersensitivity reactions - 27Cremophol EL requires ---------- as premedsH1 & H2 antagonists
- 28What is the purpose of Cremophor® EL in taxane and microtubulin inhibitors formulations?to improve solubility
- 29vinorelbine (Navelbine®) is used for ---?metastatic breast cancer
- 30Antimetabolites1. Gemcitabine
2. Capecitabine *** - 31Capecitabine is available in tablets form as ------------- prodrug?5-Fluorouracil prodrug
- 32Capecitabine is an elegant drug in that it allows for -------- concentrations of --------- (the active product provided by 5-FU) in cancerous cells than in normal cells.1. higher
2. 5-F-dUMP - 33Activation of 5-FU through several steps to yield a metabolite which targets thymidylate synthase and acts as a suicide inhibitor is an MOA of -------------- drugs?Antimetabolite = Capecitabine
- 34Capecitabine SEs are ----- ?1. bone marrow suppression
2. N / V/ D
3. “hand-and-foot syndrome” - 35How do you identify drug leakage caused by “hand-and-foot syndrome”?1. redness
2. tenderness
3. numbness/tingling
4. peeling of the palms and sole that
looks like sunburn. - 36capecitabine carries a black box warning of a -------?potential to increase the anticoagulating effects of warfarin
- 37Antibodies (moAb) that TARGETS HER2/neu and HER2(+)1. Trastuzumab
2. Pertuzumab
3. Trastuzumab Hyaluronidase (Herceptin Hylecta®)
4. Ado-trastuzumab emtansine (Kadcyla™)
*** They both target different epitopes. Hence, can be used in combination for greater effects. - 38Trastuzumab (Herceptin®) and pertuzumab (Perjeta®) MOA ---?1. inhibit HER2 homo- or heterodimerization ==> block tyrosine kinase activity which normally leads to cell growth due to downstream signaling,
2. mark the breast cancer cell for attack via activation of antibody-dependent cellular cytotoxicity
3. inhibit HER2 stimulated blood vessel growth (angiogenesis) in the tumor. - 39Trastuzumab (Herceptin®) and pertuzumab (Perjeta®) SEs are -----?1. Hypersensitivity
2. cardiotoxicity - 40Trastuzumab (Herceptin®) and pertuzumab (Perjeta®) BBW is ----?1. Infusion-related toxicity (hypersensitivity)
2. Cardiotoxicity
3. pulmonary toxicity - 41What are pretreatment drug recommendations for Trastuzumab (Herceptin®) and pertuzumab (Perjeta®) in other to avoid infusion related toxicitity?1. APAP
2. Benadryl (diphenhydramine) - 42What is the difference btw Trastuzumab (Herceptin®) and Ado-trastuzumab emtansine (Kadcyla™)1. Ado-trastu is a HER2-antibody drug conjugate which incorporates the HER2 targeted actions of trastuzumab with the microtubule inhibitor DM1 (aka. Mertansine)
2. The conjugate allows for selective delivery of the cytotoxic agent (DM1) into HER2 overexpressing cells, resulting in cell cycle arrest and apoptosis via a mechanism similar to that of the vinca alkaloids. - 43Ado-trastuzumab emtansine (Kadcyla™) BBW includes ----?1. Cardiotoxicity (evaluate pt Q3mo)
2. Hepatotoxicity (Monitor transaminases & bilirubin at baseline and b4 each dose) - 44DM1 is associated with1. peripheral neuropathy
2. bone marrow suppression
3. extravasation reactions - 45Fam-trastuzumab deruxtecan-nxki (Enhertu®) indication is -----?approved for unresectable or metastatic HER2(+) breast cancer in patients who have received two or more prior anti HER2-based regimens in the metastatic setting.
- 46Fam-trastuzumab deruxtecan-nxki (Enhertu®) MOA?1. targets HER-2 with a small molecule,
DXd (a topoisomerase I inhibitor) which attached to the antibody by a cleavable linker.
2. membrane permeable DXd causes DNA damage and apoptotic cell death. - 47Fam-trastuzumab deruxtecan-nxki (Enhertu®) AES1. Cardotoxicity
2. fatigue
3. Nausea and vomiting
4. alopecia
5. constipation
6. decrease appetite
7. anemia
8. neutropenia
9. diarrhea
10. leukopenia
11. cough
12. thrombocytopenia.
Warnings and precautions include interstitial lung disease and pneumonitis which have resulted in death. - 48Kinase Inhibitors are1. Lapatinib (TKI [tyrosine kinase inhibitor])
2. Neratinib (“pan- EGFR TKI inhibitor) - 49Lapatinib and Neratinib MOA?bind to the kinase domains of activated EGFR (ErbB1) and other HER (ErbB) receptors, preventing their ability to phosphorylate downstream signalling proteins, thereby preventing transmission of growth signals
- 50Lapatinib and Neratinib AEs ---?Hepatotoxicity
*** BBW for Lapatinib but not for Neratinib
rash
nausea
fatigue
Severe diarrhea (aggressively managed with loperamide prophylaxis) - 51Lapatinib (Only) SEs ---?1. risk of cardiotoxicity - decreases in left ventricular ejection fraction (LVEF) and heart failure (less severe than trastuzumab) 2. pulmonary toxicity (interstitial lung disease (ILD) and pneumonitis), and
3. QTC elongation - 52Lapatinib BBW“Hepatotoxicity"
- 53Lapatinib indication ---?1. approved for use in HER2(+) patients with brain metasteses,
2. in those who have prior exposure to trastuzumab, anthracyclines, or taxanes, or
3. in those with an indication of hormone therapy. - 54Neratinib (Nerlynx®) indication ----?approved for use in combination with capecitabine in patients with advanced or metastatic HER2(+) breast cancer who have received 2 or more prior anti-HER-2 based regimens.