what is Klinefelter syndrome?XXY male that produces more estrogen than normalhow long will hormone sensitive breast cancers be treated?5-10 years to suppress cancer recurrencethe choice of hormonal treatment in breast cancer depends on what?menopausal status of the patientHormone sensitive breast cancer: premenopausal? postmenopausal?pre: Tamoxifen Post: Aromatase inhibitorwhen would an Aromatase inhibitor be used in hormone sensitive breast cancer?postmenopausal womenwhen would Tamoxifen be first line in breast cancer?hormone sensitive premenopausalall breast tumors express what two receptors?estrogen and progesteronewhy are aromatase inhibitors NOT useful in premenopausal women?Premenopausal women still produce ovarian estradiol AIs do not block ovarian estradiol production; they work better at blocking conversion of androgenswhat drug is used for osteoporosis prevention and treatment but also breast cancer prohpy?Raloxifene (SERM)In some circumstances, premenopausal women will be put into menopause by taking what?GnRH agonist: goserelin or leuprolidehow do GnRH agonist work to put a woman into menopause?goserelin or leuprolide will decrease LH and FSH, which suppresses ovarian estradiol production this will make AI a reasonable treatmenthow does treatment of HER2+ breast cancers work?they prevent dimerization of HER2when you see HER2+ breast cancer, think of what drug??Trastuzumab (Herceptin)What are some primary chemotherapy drugs used for breast cancer? (7)capecitabine carboplatin cyclophosphamide docetaxel paclitaxel doxorubicin MTXwhen would you use CDK4/6 inhibitors as first line in breast cancer?in combo with hormone tx in metastatic breast cancerBreast cancer: when you see tamoxifen, what DDI should you think of?2D6 inhibitors: paroxetine and fluoxetine tamoxifen is prodrug that gets activated by 2D6what is the preferred tx for hot flashes/night sweats while taking tamoxifen?venlafaxinemechanistically, why is raloxifene used in breast cancer prophy?SERM: estrogen antag in breast BUT also estrogen AGONIST in bone, good for bonesBreast cancer: what drug is a selective estrogen receptor degrader? (SERD)Fulvestrant (Faslodex) IM injectionBreast cancer: aromatase inhibitors have a higher risk of what? (2)osteoporosis CVDBreast cancer: Aromatase inhibitor ADEs?hot flashes/sweats arthralgia/myalgiaProstate cancer: a PSA of ____ likely indicates prostate cancer?>10 ng/mlProstate cancer: what are the primary hormones that are blocked when treating prostate cancer?testosterone and its active metabolite, DHTProstate cancer: hormonal treatments are called Androgen Deprivation Therapy (ADT) which is also called what?chemical castrationProstate cancer: what are some common ADEs of ADT?impotence weakness hot flashes loss of bone densityProstate cancer: how is ADT acheived?GnRH antagonist (alone) OR GnRH agonist, initially taken with an antiandrogenProstate cancer: what is needed when using a GnRH agonist?antiandrogen initially until negative feedback kicks inProstate cancer: what are some GnRH agonists? (2)Leuprolide (Lupron Depot) Goserelin (Zoladex)Prostate cancer: what are some GnRH antagonists?Degarelix (Firmagon) Relugolix (Orogovyx)Prostate cancer: what are the first generation Antiandrogens? (3)Bicalutamide Flutamide NilutamideProstate cancer: what are the second gen antiandrogens? (3)Apalutamide (Erleada) Darolutamide (Nubeqa) Enalutamide (Xtandi)Prostate cancer: what is an androgen biosynthesis inhibitor? what must be used with it?abiraterone (Zytiga) use with prednisone to cause neg feedbaclChemotherapy: combination regimens are usually admin in _____ cycles2-6 week cyclesChemotherapy: what chemo classes are cell cycle INDEPENDENT? remember: All Awesome PharmacistsAlkylating agents: cycloph, ifos Anthracyclines: doxo, mitox Platinum compounds: cisplatin, carboChemotherapy: G1 phase chemo drugs? (3)asparaginase, interferons, steroidsChemotherapy: S phase chemo drugs? (2) remember: AT the S phase, DNA replicATesAntimetabolites: MTX, 5-FU, capecitabine Topo I inhibitors: irino, topotecanChemotherapy: G2 phase chemo drugs? (2)topo II inhibitors: etoposide, bleomycinChemotherapy: M phase chemo drugs?Taxanes: paclitaxel, docetaxel Vincawhat is the mosteller BSA equation?sqrt [(cm x kg)/3600]what are the average BSA for adult men? women?men: 1.9m2 women: 1.6 m2Cell cycle indep agents: Alkyl agents which drugs in this class produce metabolite, acrolein?cyclophos and ifosfamide can cause hemorrhagic cystitis: use mesnaCell cycle indep agents: Alkyl agents how must carmustine be supplied?non PVC bag and tubingCell cycle indep agents: Alkyl agents what 4 main drugs are used in this class?cyclophos ifos busulfan carmustineCell cycle indep agents: Alkyl agents what drug in this class is pink when decomposed?dacarbazineCell cycle indep agents: Alkyl agents what color does dacarbazine turn when decomposed?pinkCell cycle indep agents: Alkyl agents what must the doctor and pharmacist relay to patient taking lomustine?do not dispense more than one dose at a time only one dose every 6 weeksCell cycle indep agents: Alkyl agents major ADE of busulfan, carmustine and lomustine?pulmonary toxCell cycle indep agents: Alkyl agents what drug in this class can cause blue green urine?mitomycinCell cycle indep agents: PLT based can cause heavy metal poisoning symptoms such as?peripheral neuropathy, ototox, nephrotoxCell cycle indep agents: PLT based which agent is associated with the highest incidence of nephrotox and CINV?cisplatinCell cycle indep agents: PLT based cisplatin doses are usually limited to what?<100 mg/m2/cycle remember: "cis" kinda sounds like centuryCell cycle indep agents: PLT based what can be given prophylactically to prevent nephrotox from cisplatin?Amifostine (ethyol)Cell cycle indep agents: PLT based when would Ethyol be given?prophy to prevent nephrotox of cisplatinCell cycle indep agents: PLT based what toxicities can happen with these drugs?nephrotox neurotox ototoxCell cycle indep agents: PLT based which drug is dosed using the Calvert formula?carboplatinCell cycle indep agents: PLT based how do you dose carboplatin?Calvert formula: (target AUC) x (GFR+25) AUC ranges from 2-8; GFR capped at 125Cell cycle indep agents: PLT based what is unique about oxaliplatin neuropathy?exacerbated by exposure to cold, including drinking cold bevsCell cycle indep agents: anthracyclines what is associated with all AC?cardiotox!!!!Cell cycle indep agents: anthracyclines what is the lifetime dose of doxorubicin?450-550 mg/m2Cell cycle indep agents: anthracyclines what is used to help prevent cardiotox?Dexrazoxane (Zinecard, Totect)Cell cycle indep agents: anthracyclines which brand name of dexrazoxane is used to treat doxorubicin extravasation?TotectCell cycle indep agents: anthracyclines special admin requirement?protect from lightCell cycle indep agents: anthracyclines what color is doxorubicin?redCell cycle indep agents: anthracyclines what color is mitoxantrone?blueCell cycle specific: topo I inhibitors what drugs are in this class? (2)irinotecan (Camptosar) Topotecan (Hycamtin)Cell cycle specific: topo I inhibitors what are unique concerns with irinotecan?acute cholinergic symptoms: flushing, sweating, abd cramps, diarrhea (treat with atropine) delayed diarrhea: treat with loperamide up to 24 mg/dayCell cycle specific: topo I inhibitors how do you treat acute phase diarrhea caused by irinotecan? delayed?atropine delayed: up to 24 mg/day loperamideCell cycle specific: topo II inhibitors what drugs are in this class? (2)Etoposide (IV, phosphate, capsules) BleomycinCell cycle specific: topo II inhibitors Etoposide IV unique concerns? (3)infusion rate related hypotension IV prep: <0.4 mg/ml to avoid precip use non PVC IV bag and tubing due to leaching of DEHPCell cycle specific: topo II inhibitors Etoposide capsules unique concerns? (3)refrigerate capsules!!!! IV:PO ratio is 1:2 doses >200 mg need to be given in divided dosesCell cycle specific: topo II inhibitors Bleomycin BW?pulmonary fibrosis!!!! anaphylaxisCell cycle specific: topo II inhibitors Bleomycin unique concerns? (2)not myelosuppressive max lifetime dose 400 units!!!!Cell cycle specific: topo II inhibitors what is the max lifetime dose of Bleomycin?400 units!!!Cell cycle specific: vinca alkaloids which drug is associated with more CNS toxicity?VincristineCell cycle specific: vinca alkaloids which drugs are associated with more bone marrow suppression?vinBlastine, vinorelBineCell cycle specific: vinca alkaloids what do you use if extravasation occurs?warm compresses and hyaluronidaseCell cycle specific: vinca alkaloids admin of vinca alkaloids?IV only!!!!Cell cycle specific: vinca alkaloids Vincristine is a major substrate of 3A4 so caution with what?azoles!!!Cell cycle specific: vinca alkaloids what toxicities are common? (2)peripheral sensory and autonomic neuropathies (constipation)Cell cycle specific: vinca alkaloids how can vincristine be prepared to avoid inadvertent intrathecal admin?prepare it as a small piggy back rather than syringeCell cycle specific: taxanes what drugs are in this class? (2)Paclitaxel DocetaxelCell cycle specific: taxanes what is a common toxicity?peripheral sensory neuropathiesCell cycle specific: taxanes what other chemo drugs pose a DDI and need to be given a certain way?cisplatin/carboplatin give taxanes before PLT compoundsCell cycle specific: taxanes Paclitaxel premedications?diphenhydramine, steroid, H2RACell cycle specific: taxanes Docetaxel premedications?steroid for 3 days starting 1 day prior to docetaxel dexamethasone; to prevent severe fluid retentionCell cycle specific: taxanes which taxane causes fluid retention?DocetaxelCell cycle specific: taxanes which taxane does not require premedication?paclitaxel albumin-bound (Abraxane)Cell cycle specific: taxanes what filter do you use with paclitaxel and cabazitaxel?0.22Cell cycle specific: pyrimidine analog antimetabolites what drugs are in this class?5-FU capecitabine (Xeloda)Cell cycle specific: pyrimidine analog antimetabolites what is given with 5-FU and why?Leucovorin inc efficacy; help 5-FU bind more tightlyCell cycle specific: pyrimidine analog antimetabolites common side effects? (3)hand foot syn diarrhea mucositisCell cycle specific: pyrimidine analog antimetabolites what is the antidote that can be given for overdose?triacetate (Vistogard)Cell cycle specific: pyrimidine analog antimetabolites what genetic testing should be done?DPD deficiencyCell cycle specific: folate antimetabolites what drug is in this class and what phase does it work on?MTX S phaseCell cycle specific: folate antimetabolites what are common toxicities when interfering with folic acid? (4)myelosuppression diarrhea mucositis nephrotoxCell cycle specific: folate antimetabolites what can be given as rescue therapy with high doses MTX?leucovorin: active form of folic acidCell cycle specific: folate antimetabolites what formulation can be given intrathecally?preservative freeCell cycle specific: folate antimetabolites what is high dose MTX?>500 mg/m2Cell cycle specific: folate antimetabolites what must be given to decrease risk of nephrotoxicity?hydration and IV sodium bicarb to alkalinize urineCell cycle specific: folate antimetabolites what is used as an antidote that will rapidly lower MTX levels that remain high despite hydration and urinary alkalization?Glucarpidase (Voraxaze)Cell cycle specific: folate antimetabolites when is liver tox a concern?used longer term for RATargeted therapy: MAb "ci" substemcirculatory system VEGF targetTargeted therapy: MAb "tu" substemtumor EGFR, HER2, cluster of antigensTargeted therapy: MAb "Li" substem?immune system targets PD-1, PDL-1, CTLA-4Targeted therapy: MAb Bevacizumab brand name? BW? unique concern?Avastin BW: fatal bleeding/GI perforation impairs wound healing: do not admin for 28 days before or after surgeryTargeted therapy: MAb Trastuzumab brand name? unique concern?Herceptin monitor LVEFTargeted therapy: MAb Cetuximab brand name? unique concerns?Erbitux test for EGFR gene expression and KRAS mutation; must be KRAS wild type to useTargeted therapy: MAb Rituximab brand name? unique conerns?Rituxan premedicate with diphen, APAP, steroid; test for B-cell CD20, it must be positive to useTargeted therapy: TKI Imatinib brand name? unique concern?Gleevec must be BCR-ABL positive to usewhich oral chemo drugs need to me taken with food or within 1 hour after a meal? (4)imatinib (gleevec) capecitabine (Xeloda) Thalidomide (Thalomid) Exemestane (Aromasin)common ADEs of TKIs? (6)hypothyroidism QT prolong acneiform rash HTN, hand foot syn hepatic tox diarrhea