Drugs Flashcards

Question

Soft tissue sarcoma chemo regimen

Answer 1

First line: doxorubicin + ifosfamide Second line: Gemcitabine + docetaxel

Answer 2

Docetaxel/Paclitaxel + vinorelbine

Answer 3

Sarcoma- GIST second line, kidney, pancreatic in PNET TKI- VEGF 1, 2, and 3 inhibitor, PDGFR a and b, c-KIT, FLT-3, CSF-1R, RET ADRs: Nausea, diarrhea, skin/hair color changes, mouth sores, weakness, low wbc/rbc,, HTN, CHF, bleeding, hand/foot syndrome, low thyroid hormone, taste changes

Answer 4

VEGF inhibitor CNS tumors, clear cell RCC (rarely), frontline/recurrent ovarian and cervical, recurrent endometrial, ***non-squamous cell*** NSCLC, HCC, colorectal -impaired wound healing-hold for 6 weeks before and 6-8 weeks after surgery (not including port-A-Cath) -bleeding ! -clotting- ***avoid if stroke hx*** -nephrotic syndrome- ***hold for urine protein 2+*** and do 24hr urine collection -GI perforation -HTN! ***HTN does NOT preclude people from getting bevacizumab especially if it’s controlled*** -proteinuria- okay if scr is fine -tracheoesophageal fistula

Answer 5

CNS tumors, bladder, testicular AUC 7 x1- only time AUC 7 is used, ovarian, endometrial, cervical, Breast, RR NHL, HL, head/neck, NSCLC, SCLC, gastric/esophageal Alkylating agent -nausea -pancytopenia -fatigue -renal toxicity -DLT: thombocytopenia -use instead of cisplatin if ***SIADH***

Answer 6

CNS tumors Alkylating agent- nitrosourea -nausea -fatigue -thrombocytopenia -lymphopenia -pulmonary toxicity -equivalent to lomustine but IV so less preferred -wafer rarely ever used -great BBB permeability

Answer 7

CNS tumors, bladder, cervical, breast, HL, NHL, MM, head/neck, NSCLC, SCLC, biliary tract, pancreatic, gastric/esophageal -N/V- biphasic -nephrotoxicity-hydrate with ***NS only*** -ototoxicity -neuropathy! -infertility! (Testicular cancer >400 mg/m2) -highly emetogenic -Thrombocytopenia -relative lack of myelosuppression -less tolerated than Carboplatin -do not give if ***crcl< 30*** -50% dose reduce for crcl 30-60 -use carbo instead if ***SIADH*** -Hydrate with NS and can use forced hydration with loop diuretic or mannitol -mannitol only shown benefit with cycle 1 and overall not compelling evidence, and diuretics don’t have convincing data to recommend -supplemental k and mg- electrolyte wasting d/t renal tubule damage -Amifostine to decrease nephrotoxicity, don’t use if good chance of survival advantage

Answer 8

CNS tumors, breast, AML, ALL, CLL with Fludarabine and rituximab -lymphomas: DLBCL, Burkitts, PMBL, HL, indolent lymphomas, MM, SCLC Alkylating agent- nitrogen mustard -N/V -myelosuppression -mucositis -hemorrhagic cystitis- hydrate, give with Mesna if: -BMT -hyperCVAD- 1.8 g/m2 -renal dysfunction -immunosuppressant -SIADH -nasal congestion if given too fast Prodrug activated by liver -caution w/ dose adjustments, not clear Cell cycle non-specific Nadir d7-12 (a bit earlier) DI: -***inducers may increase bio activation and increase toxicity*** -3A4 inhibitors

Answer 9

CNS tumors, recurrent ovarian, AML, DLBCL, PMBL, BL, HL, MM, NSCLC, SCLC Topoisomerase II inhibitor, epipidophylotoxin -hypotension- slow infusion -DLT-myelosuppression -N/V- low-mod -secondary malignancy AML There is a PO option - ***very erratic absorption*** Cell cycle specific ***non-PCV bag and low sorting infusion set*** Works in G2 (like bleomycin) phase and S phase of cell cycle

Answer 10

CNS tumors, SCLC, pancreatic, gastric/esophageal, colorectal Topoisomerase I inhibitor -camptothecan Prodrug- SN38 is active metabolite ADRs: -diarrhea (***acute within 24hrs*** d/t cholinergic storm- tx w/ atropine, ***late >24h*** tx w/ loperamide) -pancytopenia/neutropenia!! -***nausea/vomiting is big*** -fatigue -does NOT cause hypotension -***myelosuppression is big*** -Cell cycle specific -Smoking decreases activity (at least toxicity and likely efficacy) ***-Use 70% of standard dose if know HOMOZYGOUS UGT1A1*28*** ***-3A4 substrate- CI with inhibitors*** (don’t ignore this!!) Don’t use with Gilbert’s dx There is a liposomal form Fun fact: bacterial in gut can convert irinotecan back to active for- so if refractory diarrhea could try cephalosporin/FQ could help Glucuronidated in liver to SN38G which is eliminated via biliary excretion into GI tract, however can be deactivated back to SN38 here

Answer 11

MTX rescue therapy- rescues healthy cells- GIVE WITHIN 42 HOURS! But usually started ***20-24 hours*** after ***start*** of MTX (too soon can reduce efficacy) Should prevent mucositis and neutropenia Rescue: 15 mg/m2 iv starting 24h after starting MTX- may end up needing much higher doses Required for ***MTX>500 mg/m2 (HD-MTX)*** but consider for 100-500 mg/m2 IV to PO is 1:1 unless at higher doses like >35 mg Used until MTX <0.1 Don’t give within 2hr of glucarpidase. Also, ***first 48h*** after glucarpidase use pre glucarpidase luecovorin dose- then dose leucovorin base on MTX lvls ***Also used to enhance activity of 5FU- allows it to bind to target enzyme better- IV over 2 hours*** (not PO) -also levoleucovorin which is usually used if leucovorin is not available ***(dosed at 50% of leucovorin dose)*** Does not prevent nephrotoxicity but does reduce GI toxicity and myelosuppression

Answer 12

CNS tumors Alkylating agent- nitrosourea -oral so preferred over carmustine -nausea -fatigue -thrombocytopenia- PLT cell line is hit the hardest (more than temodar) -lymphopenia -pulmonary toxicity -dispense 1 RX at a time to avoid patient overdose possibility -prolonged nadir 4-6 wks -give at night with 5HT3 blocker -great BBB permeability

Answer 13

CNS tumors, HL Alkylating agent- methylhyderazine -PO -MAO-I activity- seratonin syndrome- beware DIs, low tyramine diet and x1 week after taking drug, could cause hypertensive crisis -nausea-give at night with 5HT3 blocker -rash -possible disulfuram like rxn -decongestants can also inc risk of HTN

Answer 14

B cell Lymphomas- DLBCL, PMBL, BL, CNS lymphoma, chronic leukemias, indolent lymphomas (FL, MCL, MZL, WM) -infusion rxn- (fever, chills, rigors, changes in BP)- most commons with first dose- don’t stop infusion, slow it down -hypersensitivity rxn (chimeric mAb) but this is quite rare -hep b reactivation -PML- due to long immunosuppression -can decrease efficacy of vaccines -risk IgM tumor flare in WM- caution if high IgM (***>4000***) -rapid infusion- if tolerated start with cycle 2- over 90 minutes (20% in 30 mins and 80% over next 60). Don’t do If CV dx or lymphocyte count >5000.

Answer 15

CNS tumors Topoisomerase II inhibitor - epipodophyllotoxin -Myelosuppression -mucositis -N/V -diarrhea -hypotension! Not used for glioma Works in G2 (like bleomycin) phase and S phase of cell cycle

Answer 16

CNS tumors, mostly just hematologic CAs, also ITP, ALL, DLBCL, PMBL, BL, HL, indolent lymphomas, SCLC Antimicrotubule -cell cycle specific -neuropathy- can be reversible! -constipation-DLT (autonomic neuropathy)! -NOT myelosuppressive! -hepatic-dose reduce for elevated bili -3a4 interactions- fluconazole ok but other azoles interact -SIADH-hyponatremia -CI in Charcot Marie tooth disease -Vocal cord palsy: tx with pyridoxime or pyridostigmine -jaw pain, trigeminal neuralgia -Veno-occlusive dx

Answer 17

Tx of toxic MTX levels with evidence of new renal impairment - 48-60 hrs from start of MTX infusion Continuous infusions -36h level>30 -42h level>10 -48h level>5 Infusions over <6h -24h level >50 -36h level>30 -42h level >10 -48h level >5 ***you still need leucovorin for intracellular MTX- glucarpidase only eliminates extra cellular MTX*** *and scr must be elevated (50%+ increase from BL) *hour markers a measured from the ***start*** of the MTX infusion -don’t give leucovorin within 2 hours -don’t repeat glucarpidase within 48 hours of first dose -immunoassay for MTX lvls are inaccurate for 48 hrs after glucarpidase.

Answer 18

Bladder, kidney, metastatic merkel cell carcinoma PD-L1 inhibitor Bladder- second line for maintenance following platinum based chemo could become SO Downside: dosed twice weekly, requires premeds when initiating therapy

Answer 19

Biological response modulator (similar to IL-2)- ***need intact immune system-no immunosuppressants*** Non-muscle invasive bladder cancer Given intravesically Used as induction and maintenance x1-3 yrs for high risk Give at least 7-14 d after TURBT- to avoid systemic absorption and ***BCG sepsis (tx with anti-tuberculosis therapy)*** Flu-like symptoms (***after 3rd dose***)- give APAP/NSAIDs, dysuria, bladder spasms (oxybutynin/tolterodine, hematuria (hold until resolution), allergic rxn (H1 ppx), exposure precautions x48hrs Don’t use in people w/ infections on ABX Compound separately from other IV and use ***containment device or respiratory protection*** Exposure precautions- caution when voiding x48h, wash hands if urine on them, bleach in toilet before flush NOT used preoperatively

Answer 20

Antimicrotubule Cell cycle specific Bladder, prostate (with pred), gyn, breast, head/neck, NSCLC, SCLC, gastric/esophageal DLT: neutropenia, neuropathy, (less than paclitaxel) ADRs: tearing, ***edema (give steroids!!***)myalgias, more neutropenia than paclitaxel, skin rxns, irritant -Dose reduce for hepatotoxicity! -3A4 substrate -***Dex 8 mg BID x3 d*** starting the day before -controversy over dose in Asians Other: -inflammatory moa -free radicals (stop vit C)

Answer 21

Antibody drug conjugate - antimicrotubule -Nectin-4 targeting antibody-drug conjugate with MMAE payload --MMAE (antimicrotubule) Metastatic Bladder- 1st line with pembro -second line: post ICI and cisplatin ineligible ADRs: skin reactions/ rash, pruritis, neuropathy, hyperglycemia ***(DKA)***, ocular toxicity ***(eye exam)***, diarrhea Loperamide prn, fragrance free lotion, ppx artificial tears, blood glucose monitoring

Answer 22

FGFR inhibitor Metastatic Bladder-FGFR/FGFR2 mutations and progressed on at least 1 line of platinum therapy (second line ) ***eye disorders***

Answer 23

Anti tumor antibiotic Bladder-NMIBC, MIBC if w/ 5-fu + RT

Answer 24

Gene therapy- intravesical High risk BCG unresponsive NMIBC w/ ***Cis*** w/ or w/o papillary tumors Delivers gene copy to bladder lining that encodes interferon-Alfa 2b that stimulates immune system to attack

Answer 25

Bladder, kidney, R/R HL, HL, melanoma, head/neck, NSCLC, SCLC, HCC, gastric/esophageal, colorectal (dMMR/MSI-H or POLE/POLD1) Immune checkpoint inhibitor -***PD-1 inhibitor*** Bladder-2nd line, no PDL1 required Give first Nivo 1 mg/ ipi 3 mg (could consider reverse to decrease ADR) For melanoma follow with nivo maintenance (240 mg q2wk or 480 mg q4wk)

Answer 26

PD-1 inhibitor Bladder- 1st line for platinum ineligible, or 2nd line, other indications

Answer 27

Antibody drug conjugate- ***SN38*** (active metabolite of irinotecan) payload is topo-I inhibitor- targets trop-2 Bladder/ mUC after platinum and IO -1) Refractory metastatic TNBC after 2 lines or 2) metastatic HR+ HER2- endocrine refractory dx or visceral crisis ( not HER2 low-l). Used instead of fam-trastuzumab if not HER2 low -Treat diarrhea with loperamide Increased risk neutropenia with ugt1A1*28

Answer 28

Antimicrotubule HL, bladder -cell cycle specific Myelosuppression Increases cisplatin ototoxicity

Answer 29

PD-L1 inhibitor Bladder- second line, NSCLC, SCLC, cholangiocarcinoma, HCC

Answer 30

CDK 4/6 inhibitor Myelosuppression prevention-given before platinum/etoposide containing regimens or a topotecan regimen for ES-SCLC

Answer 31

Treats Veno-occlusive dx which is emergency type of hepatotoxicity often caused by drugs that have ozagamicin Gemtuzumab ozagamicin Inotuzumab ozagamicin VOD usually happens in first 3 weeks after transplant

Answer 32

ALK inhibitor, ***ROS-1*** Sarcoma, NSCLC-ALK ADRs: ***fatigue, constipation, edema, myalgia,*** visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD -***early pulmonary toxicity***- dose titration: 90 mg QD x7 d—> 180 mg QD -CNS penetration

Answer 33

ALK inhibitor, ROS1 Sarcoma, NSCLC- ALK/ROS1, ***MET exon 14 skipping mutation*** ADRs: ***fatigue, constipation, edema, myalgia,*** visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, IL, ***low testosterone*** -moderately emetogenic -renal dose

Answer 34

ALK inhibitor NSCLC- ALK, ***ROS1*** ADRs: ***fatigue, constipation, edema, myalgia,*** visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD -MOST CNS penetration -CNS ADRs (nightmares, hallucinations, depression) -***NEUROPATHY*** -***hypercholesterolemia***- tx with statins don’t dose reduce -weight gain -option for resistant mutations: ***ALk G1202R, L1196M, (except compound L1196M/G1202R)***

Answer 35

Kidney TKI- VEGF inhibitor ADRs: HTN, fatigue, N/V/D, poor appetite/wt loss, voice changes, hand/foot syndrome, constipation. HTN, bleeding, clotting, wound healing, lfts, hypothyroidism Short t1/2: quick onset of large dx burden and quick offset if ADRs Titrated up. Lots of doses to go up or down as needed. Unlike most tkis where we start at max dose then go down, this one can go higher or lower than starting dose

Answer 36

Von-hippel-lindau (VHL) associated RCC ***after PD-L1 and VegF*** Also VHL associated: CNS hemangioblastoma, pancreatic neuroendocrine tumors Hypoxia inducible factor inhibitor ADRs: ***anemia (hold for Hgb<8)***, fetal embryo toxicity, fatigue, dyspnea, nausea, HA, hyperglycemia, hypoxia 3A4 Enzyme Inducer- birth control failure!

Answer 37

Kidney, thyroid, HCC (2nd line) TKI- VEGF inhibitor, MET, AXL, ***RET*** ADRs: N/V/D, ***diarrhea***, fatigue, poor appetite/ wt loss, ***HTN,*** hand/foot syndrome, constipation. ***Bleeding,*** clots, ***intestinal perforation, fistulas*** -hold 3 weeks before and 2 weeks after surgery (wound healing) -mod-high emetogenic -empty stomach -higher risk of hand/foot syndrome than other VEGF inhibitors Thyroid: Tablets (cabometyx-140 mg QD) and capsules (cometriq- 60 mg QD) are not interchangeable RCC monotherapy: 60 mg (can be tough to tolerate) RCC combination: 40 mg -Long t1/2 with active metabolites so keep in mind if surgery coming up and need to hold -good if bone dx

Answer 38

Kidney, recurrent endometrial (w/ letrozole), breast cancer, WM, pancreatic mTOr kinase inhibitor ADRs: immunosuppressive, mouth sores (use dex mouthwash), nausea, loss of appetite, rash, diarrhea, fatigue, edema, hyperglycemia, hypercholesterol. Rare lung damage ***DLT: mucositis- use dexamethasone mouth rinse (solution NOT elixir- (etoh free))*** QID no food within an hour ***NOT hand/foot syndrome***

Answer 39

Kidney Ca Rarely used d/t AE and better therapies available *need excellent PFS and good renal function

Answer 40

Kidney, Melanoma, NSCLC, HCC, -colorectal (if dMMR/MSI-H, or POLE/POLD1. Only in combo with nivo) Immune checkpoint inhibitor- anti CTLA4 mAb First FDA approved ICI

Answer 41

Kidney, recurrent endometrial, melanoma, thyroid, HCC, biliary tract TKI- VEGF 1, 2, and 3 inhibitor; FGFR 1, 2, 3, and 4 inh, PDGFRa; c-KIT, and RET ADRs: , diarrhea, ***N/V/D,*** proteinuria, ***fatigue, decreased appetite.*** joint/muscle pain, swelling of arms/legs. Bleeding, clots, ***severe HTN,*** intestinal perforation, kidney/liver/heart failure, hypothyroid, mucositis, hypocalcemia -voice hoarseness (reversible and not dose related) -mod-high emetogenic- ***GIVE with ANTIEMETIC*** -hold 1 wk before and 2 wks after surgery (wound healing) “Poorest tolerated option, except Tivozanib” “More hand-foot/mucositis”

Answer 42

-Kidney- historically used but not anymore except certain circumstances -Thyroid -HCC cat 1 TKI- VEGF inhibitor, FLT-3-ITD, RET ADRs: fatigue, rash, diarrhea, HTN, hand/foot syndrome, cardiotoxicity, LFTs, QTc, wound healing impairment, bleeding -empty stomach

Answer 43

Kidney- historically used but now only under certain circumstances, endometrial mTOR kinase inhibitor ADRs: mouth sores, rash, nausea, loss of appetite, edema in face/legs, hyperglycemia, hypercholesterol,

Answer 44

Kidney- after 2 prior therapies TKI-VEGF inhibitor- blocks all three VEGF receptors, c-KIT, PDGFR-beta ADRs: nausea, diarrhea, HTN, poor appetite, cough, mouth sores, fatigue, voice changes, bleeding, clotting, wound healing, thyroid, kidney, heart problems, allergy to excipient (yellow 5) 3A4 substrate Long t1/2 Cyclic dosing (3on 1 off) unlike other tkis in RCC

Answer 45

Prostate- only for de novo metastatic dx Anti-androgen mCSPC and mCRPC Give with prednisone: -***non-metastatic: once daily -mCSPC: 5 mg PO daily -mCRPC: 5 mg PO Twice daily*** 500 mg fine particle formulation=1000 mg of original- give w/ Methylprednisolone 4 mg BID Food affects absorption: 1000 mg give on empty stomach, 250 mg give with breakfast Adrs: hepatotoxicity, HTN, ***hyper/hypoglycemia*** ***caution if cardiac history***

Answer 46

Prostate Antiandrogen m0CRPC (delays mets), m1CSPC 240 mg PO daily ADR: -crosses BBB- falls, seizures. This is CLASS EFFECT -diarrhea, rash, hypothyroidism, ***HTN***, fractures Drug interaction! Inducer!!! Some post hoc data about safety with Apixaban/rivaroxaban

Answer 47

Prostate Antiandrogen No monotherapy- use with LHRH agonist or antagonist to prevent tumor flare ADR: -class effect- crosses BBB: ***falls, seizures, diarrhea***

Answer 48

Prostate (give with pred or dex) Taxane- antimicrotubule m1CRPC, must try docetaxel first 20 mg/m2 standard- if 25 mg/m2 give with G-CSF Less fatigue and asthenia than docetaxel ***DIARRHEA***, and FN (intermediate) Contains polysorbate 80 and ethanol Non-PCV and low sorting infusion set Premeds: steroid, h1, h2

Answer 49

Prostate- m0CRPC, m1CSPC with docetaxel Antiandrogen m0CRPC, evidence for triple therapy for newly diagnosed, de novo metastatic, high risk/volume CSPC Different from enazalutamde and apalutamide- different structure Reduced CNS toxicity- doesn’t cross BBB penetration- less fatigue and falls May be more effective in long run-works against mutated receptors Give with food! ***Less*** drug interactions: weak inducer ***Renal and hepatic dose adjustment*** 600 my BID ***with food*** ***HTN*** ***Only one that is TWICE DAILY***

Answer 50

Prostate GnRH antagonist - ***SubQ, monthly*** Cornerstone of therapy- continue throughout dx regardless of progression Monthly injections Adrs: -***inj site rxns-*** can be pretty nasty -anaphylaxis -hot flashes -metabolic syndrome Preferred over LHRH agonist when tumor flare is big concern (spinal cord compression/injury)- ***no need for antiandrogen*** Achieved castration in <7d, unlike 28 days for agonist ***Monthly only***- LHRH agonists can be given much less often depending on dose May have cv benefit over LHRH agonists in pts with high cv risk

Answer 51

Prostate Anti-Androgen m0CSPC, m0CRPC, m1CRPC, m1CSPC CNS ADRs: falls, seizures, ***HTN***, fractures Drug interactions! Inducer! 160 mg daily

Answer 52

Prostate, breast GnRH agonist Prostate: Cornerstone of therapy and should be continued throughout dx course regardless of progression Breast: premenopausal with AI of tamoxifen for ovarian suppression Adrs: -tumor flare (bone pain, urinary sx) -hot flashes -metabolic syndrome ***give with first gen antiandrogen for first few weeks*** -***SubQ***

Answer 53

***discontinued by manufacturer*** Prostate GnRH agonist Cornerstone of therapy and should be continued throughout dx course regardless of progression Adrs: -tumor flare (bone pain, urinary sx) -hot flashes -metabolic syndrome ***give with first gen antiandrogen for first few weeks*** Not listed in guidelines but approved for palliative tx

Answer 54

Prostate, breast GnRH agonist Prostate: Cornerstone of therapy and should be continued throughout dx course regardless of progression Breast: premenopausal, in combo with AI or tamoxifen for ovarian suppression Adrs: -tumor flare (bone pain, urinary sx) -hot flashes -metabolic syndrome ***give with first gen antiandrogen for first few weeks*** Not all leuprolide products are the same regarding formulation, dosing, and route -***SubQ,*** IM -can cause hyperglycemia

Answer 55

Prostate Radiopharmaceutical PSMA-positive mCRPC ***previously treated with ADT and taxanes!!*** ADrs: fatigue, dry mouth, nausea, anemia, kidney injury, myelosuppression, GI-constipation, infertility, embryo fetal toxicity, wt loss, radiation exposure -Avoid close contact x3-7d -premed w/ antiemetic

Answer 56

Prostate- m1CRPC- for palliation with no other tx options. QOL benefit but no OS benefit, AML Topo-II inhibitor, anthracycline Very cardiotoxic Different structure from other anthracyclines so less cross resistance (why it’s used in refractory setting in AML) Blue

Answer 57

PARP inhibitor Prostate- m1CRPC with any HRRm mutation except PPP2R2A- after androgen receptor therapy, ovarian Breast: if germline BRCA 1/2 mutation, early stage, and ***HER2-negative*** -adjuvant x1year- started after surgery, RT and chemo (start at least 2 wks after RT) Pancreatic- if germline BRCA mutation Myelosuppression!!! fatigue, nausea, bowel changes (constipation) Pneumonitis, increased scr Drug interactions, no grapefruit Tablets and capsules are NOT interchangeable- capsules mostly phased out of US market With or without food

Answer 58

Prostate m1CRPC- ***symptomatic*** bone dx Radiopharmaceutical Not used often Targets bone mets, not for visceral Mets! IV monthly x6 months Not just a palliative drug like some other radiopharmaceuticals Myelosuppression! First dose requires: -anc >1500, plt >100, Hgb >10, Subsequent: -anc>1000, plt >50, Don’t use with chemo or other drugs other than ADT and BMA- d/t additive myelosuppression ***Give with BMA***

Answer 59

***NCCN states not to use with other prostate cancer meds at this time (no interaction studies***- so probably better for m0CSPC- great for ***intermittent ADT*** Prostate GnRH antagonist Requires loading dose, reload if stopped for >7days Fast onset and offset- ***compliance is critical***- don’t give if pt with poor compliance!! Potential for ***less CV ADRs*** than leuprolide ***Qtc, diarrhea*** Only ***oral*** option for ADT Used as a ***single agent!*** ***no need for antiandrogen***- used for pts who need ADT alone! ***Dont use in combination with other prostate drugs!!***

Answer 60

Prostate-m1CRPC w/ BRCA mutation- after androgen receptor and taxane therapy , ovarian (BRCAm) Pancreatic- germline or somatic BRCA of PALB mutation PARP inhibitor Myelosuppression, fatigue, nausea, bowel changes (constipation) -***Hypercholesterolemia***, elevated AST/ALT, increased scr, ***photosensitivity***, MONTHLY CBC Drug interactions - less than Olaparib, grapefruit ok With or without food

Answer 61

Prostate CA vaccine Metastatic CRPC, ***No visceral mets,*** need good PFS and ***>6 mo life expectancy*** and ***minimal symptoms*** Not used often 3 doses are given Well tolerated

Answer 62

Prostate- m1CRPC- given in combination with enzalutamide for HRR+ dx Breast: metastatic germline BRCA1/2 mutation PARP inhibitor ADRs: -myelosuppression-more than Olaparib!!!!esp anemia! -fatigue -nausea Oral Dose reduce with p-gp inhibitors Renal dose adjustment

Answer 63

Prostate GnRG agonist Cornerstone of therapy and should be continued throughout dx course regardless of progression Adrs: -tumor flare (bone pain, urinary sx) -hot flashes -metabolic syndrome Not frequently used ***give with first gen antiandrogen for first few weeks*** ***Intramuscular***

Answer 64

Pediatric Neuroblastoma Anti-GD2 mAb- ***it’s a type of immunotherapy*** 10-20 hr infusion x4 days (do not exceed 20 hr infusion) -pain- need continuous opioid infusion!, infusion rxn, hypotension, capillary leak (give with albumin), cough, ocular/visual issues, electrolyte disturbances, myelosuppression bleeding, electrolyte abnormalities, increased risk infection, vision changes, No pregnancy or breastfeeding, pre-meds with ***NS, APAP Benadryl*** (not dex- ***reduces efficacy***), and antiemetics, infusion rxn, n/v ***pre meds, pre-hydration, opioid infusion, albumin*** (keep albumin >3) Slow infusion to increase tolerance ***contraindicated with steroids***

Answer 65

Testicular CA, Hodgkin’s lymphoma -***not myelosuppressive*** -max lifetime dose of 400 ***units*** -anaphylactiod rxn- do test dose for lymphoma (debatable) and ***premeds with APAP and h1***!!! -hyperpigmentation of skin -NS only -reynauds -CI w/ ***brentuximab vedotin*** and w/in 24h G-CSF (debatable) -measure DLCO- consider stopping if >25% decrease from BL (workbook says decrease ***of 40-60%)*** -avoid if BL DLCO <75% predicted (in general ***DLCO >60% is acceptable)*** -G-CSF- ok with testicular cancer, not ok if HL ***(unless BEACOPP)*** -note: NCCN specifically speaks to 60% rule but doesn’t discuss how much DLCO must decrease in order to stop -works in ***G2*** phase of cell cycle (like topo inhibitors) -RENAL dose adjust!! ***GLYCOPEPTIDE antibiotic*** Binds iron and oxygen to for free radicals and kills dna in g2

Answer 66

May be substituted for etoposide in patients with etoposide allergy Equivalent doses

Answer 67

Platinum- alkylating agent -Testicular CA-3rd line with gemzar -R/R NHL, HL, pancreatic, gastric/esophageal, colorectal -Qtc!! -cold sensitivity- resolves in 3-5days but this can lengthen with each infusion -peripheral neuropathy- ***can be permanent*** (related to cumulative dose) -neurotoxicity/neuropathy- can prolong infusion to ***6hr*** and can give ca/mg (not recommended d/t lack of evidence -there is ***acute*** (paresthesias, dysesthesias, hypoesthesias, breathing sensation loss, etc.) and ***chronic*** PN) neurotoxicity -neuropathy d/t oxalate metabolite chelating ca/mg and opening voltage gated ca channels -could use heat, acupuncture, or duloxetine -coasting- neuropathy may worse over first 3 months of discomtinuation -PN could be permanent in some cases

Answer 68

Antimicrotubule Testicular ca-second line, ovarian, endometrial, Breast cancer, head/neck, NSCLC, SCLC, gastric/esophageal Myelosuppression- worse with 24h infusion- so we don’t do this, ***Less if given weekly vs q21d*** DLT: Peripheral neuropathy - ***worse with weekly compared to q21d*** Hypersensitivity rxn d/t cremephor -premed: diphen, famot, dex -non-PVC Line w/ 0.22 micro filter bc cremephor can leach DEHP Mild vesicant-warm v cold debatable DI: -increases dox when given after, so give dox—->paclitaxel -cisplatin increases paclitaxel, so give paclitaxel —->cisplatin Taxol syndrome- arthralgias/myalgias, likely a type of neuropathy Cell cycle specific Caution in liver impairment Cremephor now called Kolliphor

Answer 69

Vinca alkaloid- antimicrotubule Testicular CA

Answer 70

***Hemorrhagic cystitis*** protectant agent -always with ifos- 20% ifos dose at hr 0, 4, and 8 (for bolus doses<2.5mg/m2/d -unless for ICE regimen you do 1:1 -for cont inf: 20% as bolus then 40% as cont inf for 12-24h after ifos completion -sometimes with cyclophosphamide -available PO but double the dose and it takes bad d/t sulfur moiety -do 20% as iv at hr 0, then 40% at hr 2 and 40% at hr 6. Repeat if vomit within ***2 hr*** (total 100%) ***IV Mesna dose is equal to 60-100% of ifos dose*** ***contraindicated in breastfeeding due to benzyl etoh*** Bad taste- take with juice or something

Answer 71

Cardioprotectant -generally for dox >300 mg/m2 -dose 10:1 -give 15-30 mins prior *metastatic BC but not adjuvant d/t possible decreases efficacy Testicular atrophy and infertility

Answer 72

Chemo protectant -prevention ***cisplatin nephrotoxicity*** -consider for decreased neutropenia- usually use g-CSF -910 mg/m2 iv over ***15 mins or less***, 30 mins before chemo- ***monitor BP*** (0 , 5, 10, 15, and 15 mins after) -***prevention of radiation proctitis in rectal cancer*** -200 mg/m2 IVP over 3 mins before each fx of RT -Can also prevent ***xerostomia and mucositis*** in RT pts for head/neck cancer- actually don’t use for mucositis…? -***avoid if good chance of cure*** -can cause ***hypotension*** (hold BP meds x24 hrs before) -premeds with NS, 5HT3, and dex -must ***give chemo within 30 mins (short half life)*** -not really used in clinical practice anymore due to inconsistent data and poor tolerability

Answer 73

Decreases severe mucositis in pts undergoing ***autologous*** SCT for a hematologic CA with ***total body irradiation*** AND ***HD chemo*** conditioning -60 mcg/kg IV x3 d before start of conditioning regimen and x3 d starting day if stem cell infusion -don’t give within 24 hours of initiation of conditioning regimen This is a keratinocyte growth factor

Answer 74

IDH 1 inhibitor -IDH1 mutated conventional and dedifferentiated chondrosarcoma -IDH1 mutated de novo or relapsed refractory AML. Given in combo with HMA or alone for unfit pts older than 75y -IDH1 mutated cholangiocarcinoma Serious ADR: differentiation syndrome, ***QTC prolongation***, high WBC, GBS, pulmonary and/or renal dysfunction 3A4 ***inducer*** Once daily (unlike olutasidenib)

Answer 75

Bladder Tis in pts who received x2 prior courses of BCG -800 mg intravesical weekly x6

Answer 76

Aromatase inhibitor- non-steroidal Ovarian CA maintenance, metastatic or recurrent endometrial Ca -Should be ER/PR positive Breast- post-menopausal, only pre-menopause if used with ovarian suppression or ablation DLT: arthralgias/myalgias

Answer 77

Anti-PD-L1 mab -Advance ***Endometrial w/ dMMR after platinum failure*** -pancreatic MSI-H or dMMR -primary advanced or recurrent dMMR or MSI-H endometrial CA combo w/ carbo and pacli —-> single agent dostarlimab -breast- MSI-H/dMMR -colorectal (dMMR, MSI-H, or POLE/POLD)

Answer 78

Aromatase inhibitor - non-steroidal -Recurrent endometrial CA -maintenance in ER/PR recurrent ovarian -breast: post menopausal (only premenopausal if ovarian suppression or ablation) DLT: arthralgias/myalgias

Answer 79

Anti-neoplastic progestin w/ anti estrogenic properties Low grade endometrial cancer

Answer 80

Anti-folate receptor alpha ***(75%)***, antibody drug conjugate- anti-microtubule (DM4) FR-a positive ***(75%+*** of cells with PS2+ staining)- ***platinum RESISTANT*** ovarian, fallopian, or primary peritoneal CA- who have received 1-3 prior systemic tx Dose in adjusted body wt due to ocular toxicity - for all BMIs!!- Don’t dose round!! Ocular toxicity - steroid eye drops day -1 x5d (6x/day)—>x4d (4x/d), lubricating drops; warm compress before sleep, sunglasses, no contact lenses -eye exam before and then every other cycles for 8 cycles D5W only Need 0.22 micro filter DM4 is a cyp3A4 substrate

Answer 81

Antimicrotubule Albumin bound paclitaxel Not used often- exhaust paclitaxel and docetaxel first Recurrent ovarian CA, endometrial, breast, NSCLC- better response in squamous ***pancreatic***, NSCLC, metastatic breast

Answer 82

PARP inhibitor Ovarian: Dose on wt and plt: 200 mg instead of 300 mg for ***wt<77kg or plt<150k*** (this is for first line maintenance only, ***if starting at a reduced dose in secondary maintenance setting, you may increase back if no thrombocytopenia*** ***DLT: thrombocytopenia*** Myelosuppression, fatigue, nausea, bowel changes (constipation), WEEKLY CBC HTN, palpitations No cyp interactions With or without food

Answer 83

Antimetabolite (pyramidine analog), ***inhibits thymidylate synthase*** -***non-squamous*** NSCLC -Gyn- recurrent dx -Give folic acid and B12- prevent severe hematologic toxicity(Start 1 wk before and continue x3 weeks after completion) ***(neutropenia)*** -Give dex 4 bid day before, of and after-prevent ***skin rash*** -crcl cut off is 45 ml/min -interacts with NSAIDs- increased pemetrexed ***Doesnt work in squamous cell bc there’s more thymidylate synthetase so you would need much higher doses***

Answer 84

SERM Ovarian maintenance in ER/PR positive Breast: pre/post menopausal Estrogenic in bones, lipids, endometrium Anti-estrogenic in breast and vaginal mucosa Increase BMD in post-menopausal but decreased in pre-menopausal Increased endometrial cancer in post-menopausal VTE, hot flashes, cataracts, ***hypertriglyceridemia, DECREASES LDL/TC, inc HLD*** Contraindicated in pregnancy Interacts with ***warfarin***- 2c9 inhibitor

Answer 85

Antimicrotubule- antibody conjugated to MMAE, target is CD142 --MMAE (antimicrotubule) Cervical cancer- recurrent or metastatic with dx progression on chemo ADR: ***ocular***, peripheral neuropathy, fatigue, nausea, epistaxis, alopecia, hemorrhage, ***rash*** -eye exam before each infusion -steroid, vasoconstrictor (prior to infusion), and lubricating eye drops -ice packs during infusion -interaction with 3A4 inhibitor s

Answer 86

Topo-I inhibitor Gyn- recurrent dx, SCLC

Answer 87

Anti-HER-2 mab -Endometrial with carbo/taxane for HER2+ -Breast: -neoadjuvant and adjuvant -for T>1 cm (consider if < 1cm) -prefer to give with chemo except anthracyclines -x1 year -HER-2+ obviously -Biliary tract- with Pertuzumab -gastric/esophageal- ***adenocarcinoma only*** -colorectal (give with lapatinib, tucatinib, or pertuzumab) Cardiotoxic , ***pulmonary toxicity,*** infusion rxn, fetal toxicity , diarrhea IV

Answer 88

-prevents cisplatin ototoxicity in kids with ***non-metastatic hepatoblastoma*** and other non-metastatic cancers -meclorethamine extravasation ***don’t use is metastatic dx***

Answer 89

Vinca alkaloid extravasation

Answer 90

Topoisomerase I inhibitor

Answer 91

Azathioprine, mercaptopurine, thioguanine, cladrabine, clofarabine, Fludarabine, nelarabine, pentostatin

Answer 92

CAR-T (anti-***CD-19)*** ->/= 2nd relapsed or refractory B-ALL on pts ***up to 25 y/o*** (only indication with this age restriction) -R/R DLBCL- ***adults*** -R/R FL (after 2+ lines of therapy)- ***adults***

Answer 93

Bispecific T-cell engager (anti-***CD19/***CD3) -Relapsed ALL, MRD+ ALL (after 3 months/cycles- after consolidation I think) frontline for ph+ given with tki -Risk for cytokine release syndrome and neurotoxicity (ICANS) -Works best with low dx burden (<50% blasts) -***For R/R ALL***28 day continuous infusion followed by 2 week break: Can do 7 day bag for home infusion (has preservative so can’t use this bag if <22kg) -***For MRD+*** hospitalize for first 3 days of cycle 1 and first 2 days of cycle 2

Answer 94

Radioconjugate for patients with relapsed or refractory Neuroblastoma

Answer 95

-NSCLC- better response in squamous -***pancreatic*** -Bound to albumin to help dissolve in solution better (normal paclitaxel needs cremephor)- -NO Premeds or inline filter/special tubing -can give faster w/o hypersensitivity rxn -kinetics are different- more free paclitaxel -better uptake into tumor cells bc CA needs amino acids -approvals: met breast ca, NSCLC, pancreatic ca -very expensive- data doesn’t necessarily show that it’s better except for… most benefit in pancreatic cancer d/t better penetration Cremephor now called Kolliphor

Answer 96

Antimetabolite (pyramidine analog) -inhibits thymidylate synthetase (continuous infusion) AND -RNA false base pair (bolus) Breast cancer, bladder, head/neck, pancreatic, gastric/esophageal, colorectal Continuous infusion for head/neck ca May need dose reduction for DPD deficiency (DPYD intermediate or poor metabolizer) ADRs: -infusion: hand-foot syndrome, ***diarrhea*** -bolus: myelosuppression ***so if neutropenia and pt is getting infusion, wouldn’t make sense to decrease dose*** -mucositis (cryotherapy w/ ice chips-30 mins before bolus) -coronary vasospasm- ***may rechallenge*** (but premeds with nitrate and calcium channel blocker- continue x48h after) Often given with leucovorin to increase efficacy -Topical form for basal cell carcinoma -radiosensitizer -photosensitizer ***(avoid sun)*** -major interaction with ***warfarin***- inhibits cyp2c9- INCREASES warfarin! -Mainly metabolized in liver via DPD -darkening if skin along veins and nails

Answer 97

CDK4/6 inhibitor Breast cancer: -use in combination with endocrine therapy !! -adjuvant therapy x2 y for high risk HR+ HER2 negative that spread to LN and high risk of recurrence: -4+ LN OR -1-3 LN + (grade 3 or T=5+cm (T3), or ki67>/=20) -OR MBC: 1st line (with AI), 2nd line (with fulvestrant +/- LHRH agonist if premenopausal) ***diarrhea-more than others!*** -less neutropenia than others in class -hepatotoxicity, VTE -increased scr (not due to renal Impairment- it inhibits tubular secretion transporter Anemia, thrombocytopenia, fatigue, infections, n/v, alopecia, weakness, interstitial lung dx For MBC with fulvestrant, preferred over Palbociclib Only CDK4/6 that is continuous therapy rather than 3 wks on 1 wk off RB1 mutation confers resistance to CKD 4/6

Answer 98

HER-2 mAb Breast cancer: 1) early stage in pts who got trastuzumab and docetaxel/paclitaxel neoadjuvant, then surgery and had cancer remaining at surgery-ADJUVANT ONLY 2) met HER2+ MBC 3rd line + Trastuzumab link to small amount of chemo to deliver chemo directly to tumor IV Emtansine is a ***microtubule inhibitor*** -Extravasation! -can give with RT (unlike capecitabine) -***tx cardiotoxicity the same as trastuzumab/Pertuzumab combo***

Answer 99

PIK3CA inhibitor , (PI3K) Breast- ***HR+, HER2 neg-***, metastatic dx-second line post CDK4/6+AI after progression -for ***post-menopause (or pre menopause with OAS*** (like all ET in metastatic breast ca)) *In combination ***with fulvestrant*** (REPLACES THE CDK4/6 INHIBITOR, and AI get switched to fulvestrant) Only for patient with PIK3CA mutation **Second line and beyond** (DONT GET TRIPPED UP!) ADR: *hyperglycemia!! (Will usually need Metformin), diarrhea, rash (consider h1 blocker), hepatotoxicity, pneumonitis

Answer 100

Antimetabolite (pyramidine analog) Breast cancer, head/neck (1250 mg/m2 BID), pancreatic, gastric/esophageal, colorectal ADR: think golf man- hand foot syndrome, diarrhea, photosensitivity -rare cardio toxicity (unlike 5FU) -ADRs worse if DPD deficiency -hyperbilirubin, angina, mild myelosuppression -don’t use if crcl<30 (use 5FU instead) -coronary vasospasm (like 5FU) DI: warfarin (2c9 inhibitor)- ***warfarin***- inhibits cyp2c9- INCREASES warfarin- more than 5FU), phenytoin, ***allopurinol*** (decreased conversion to 5FU), PPIs -More toxicity in US (like folate deficiency) so we give 1000 mg/m2 -available as 150 mg and 500 mg tabs -consider barriers in pt with upper GI cancer (crush-ability, absorption) -I think more diarrhea and hand foot syndrome than 5FU Mainly metabolized in liver via DPD

Answer 101

AKT inhibitor Breast HR+, HER-2 (-), with one or more PIK3CA or AKT1/PTEN alteration Second line Give with fulvestrant ***VERY similar to alpelisib but addition of AKT1/PTEN*** ADRs: hyperglycemia, rash

Answer 102

Endocrine therapy- SERD ***HR+, HER2 neg***, must have ESR1 mutation-***metastatic*** breast ca- ***post menopausal*** after at least 1 prior line of therapy (in the metastatic setting)- not first line (DONT GET TRIPPED UP) ***Given alone, unlike alpelesib which is with fulvestrant*** First oral SERD Oral- Take with food Adr: dyslipidemia ***emetogenic***

Answer 103

Anthracycline Breast cancer

Answer 104

Aromatase inhibitor -steroidal Breast- post menopausal (only premenopausal if ovarian suppression or ablation)

Answer 105

HER-2 mAb -Dxd/DX8951 (MAAA-1181a) topo-1 inhibitor Breast cancer: (5.4 mg/kg) -metastatic ONLY: HR+/HER2- (really HER-2 low) AND endocrine refractory- this is second line if HER2 low (IHC 1+ or 2+ and fish negative) -NSCLC-HER2 (lower dose- 5.4 mg/kg) -gastric/GEJ: prior trastuzumab (5.4 mg/kg) -gastric: 6.4 mg/kg -colorectal (HER2+, 5.4 mg/kg) -now any solid tumor with no other options Monitor for ***interstitial lung dx!*** (more than emtansine) IV Deruxtecan is topo-1 inhibitor ***cardiotoxicity***- hold for LVEF drop below 40% or >20% from BL or If LVEF 40-45 and drop is 10-20% recheck it in 3 wks and permanently stop if not recovered

Answer 106

Endocrine therapy-SERD (kinda like elacastrant) Breast- ***post menopausal (premenopausal if ovarian suppression or ablation)*** not previously tx with ET and in women w/ progression on ET Intramuscular- thick/viscous and painful, 2 injections

Answer 107

Antimicrotubule, epothilone B analog Metastatic breast cancer after failure of anthracycline, taxane, and capecitabine … or in combination with capecitabine after anthra and taxane failure ADR: neutropenia, neuropathy, hypersensitivity (give premeds- h1/h2) Non-PVC and low sorting infusion set

Answer 108

HER-2 oral TKI -Breast cancer metastatic only: (with trastuzumab or capecitabine) -colorectal (HER-2 + and RAS/BRAF wildtype. Must give w/ trastuzumab) ADR: diarrhea Oral QTc Without food

Answer 109

HER2 targeted -Metastatic only Breast cancer- after at least 2+ HER2 therapies (one in metastatic setting ) -given with chemo, replaces trastuzumab IV ***Cardiotoxic***- monitor LVEF within 4 wks before and q3 months during and after tx. Hold for dec 16% or 10% to below 50%/hospital limits (like trastuzumab). D/c if >8 wks or 3+ holds CD16A-158F may predict benefit over trastuzumab

Answer 110

HER2 oral TKI Breast- ADJUVANT ONLY X1 yr ***following*** 1 yr of ***trastuzumab:*** LN+, HR+, HER-2+ *Diarrhea- prophylactic loperamide for ***first 2 cycles (8 weeks)*** or ***2 week*** dose escalation (120 mg—>160 mg—>240 mg) Oral With food PPI/h2 interactions

Answer 111

CDK4/6 inhibitor Breast: MBC: in combo with endocrine therapy (AI (1st line) or fulvestrant (2nd line) +/- LHRH agonist if premenopausal) -Primary toxicity is ***neutropenia*** -QTc prolongation , anemia, thrombocytopenia, fatigue, n/v, infxns, alopecia, weakness, interstitial lung dx RB1 mutation confers resistance to CKD 4/6

Answer 112

Her2 -Breast cancer- must give with trastuzumab -biliary tract cancers- must give with trastuzumab -colorectal (RAS/BRAF wildtype. Also must give with trastuzumab) Neoadjuvant and adjuvant Early stage: Add to trastuzumab if ***T > 2cm or LN positive*** Give x1 year Preferentially give with chemo (except anthracyclines) ***diarrhea*** more than trastuzumab IV

Answer 113

HER2 Breast-neoadjuvant and adjuvant SubQ

Answer 114

SERM Breast cancer in ***post menopausal*** Use over AI if poor BMD, use over tamoxifen if intact uterus Clotting risk

Answer 115

CDK4/6 inhibitor -PREFERRED OUT OF THE 3 Metastatic Breast- MBC in combination with endocrine therapy (AI (1st line) or fulvestrant (2nd line) +/- LHRH agonist if premenopausal) ***Qtc prolongation***, neutropenia/leukopenia, hepatobilliary toxicity, N/V, infxns, alopecia, anemia, thrombocytopenia, fatigue, weakness, interstitial lung dx RB1 mutation confers resistance to CKD 4/6 ***3A4 inhibitor*** (Pablo is weak inhibitor and abem is not at all)

Answer 116

RET kinase inhibitor, also ***VEGF*** Metastatic breast cancer RET+, thyroid, NSCLC- RET, HCC-RET+, pancreatic-RET+, colorectal (off label, RET+ ADR: ***hypersensitivity***, HTN, interstitial lung dx, hemorrhagic events, liver toxicity, impaired wound healing, edema, ***QTc*** (unlike pralsetinib!! Caution with afib), inc TC, ***hypothyroidism*** -avoid acid reducing agents -take with food if taking with ***PPI*** -3A4 interactions (like pralsetinib) -wt based dosing -good response with brain Mets -50 kg+ 160 mg bid, <50 kg 120 mg bid

Answer 117

SERM Metastatic breast cancer- infrequently used

Answer 118

LHRH agonist Breast: premenopausal in combination with AI or tamoxifen for ovarian suppression ***IM***

Answer 119

HER2 oral TKI- more selective than others (like Neratinib, so less ADRs) -Breast: refractory metastatic only: HER2+ in combo with trastuzumab + capecitabine -colorectal (RAS wildtype, HER2+, unresectable/metastatic that progressed on fluoropyrimidine, Oxaliplatin and irinotecan based chemo Good activity with brain mets Oral *strong 3a4 inhibitor, increases scr!!, diarrhea, lfts

Answer 120

Alkylating agent (nitrogen mustard)- has purine analog in structure -Chronic leukemia in combo with rituximab or obinutuzumab -DLBCL and HL -***indolent lymphomas***, WM -SCLC Nadir- 3 wks- so we usually give q28d -Infections, severe rash (3%), infusion rxn, extravasation, secondary malignancy, TLS (incr risk rash w/ allopurinol), hepatotoxicity -DLT: ***myelosuppressive*** (***lymphompenia***, neutropenia, thrombocytopenia) -consider ***pjp and HSV ppx*** -bendeka (over 10 mins) has largely replaced treanda (over 60 minutes) -cyp1A2 -omit when bridging to CAR-T -not recommended if crcl <40 (generally decrease by 20% for crcl <50 or 40% for crcl<30) -smoking can affect metabolism (like erlotinib and irinotecan)

Answer 121

Alkylating agent- nitrogen mustard Uveal Melanoma (hepatic delivery kit for liver directed therapy)- ***Liver is most common site of metastases for uveal melanoma*** REMS d/t peri procedural complications ADRs: Extreme hematologic toxicity, GI toxicity, black box (hemorrhage, hepatocellular injury, thromboembolic events), hypersensitivity, ***VOD*** MM (oral) in non-transplant eligible pts

Answer 122

Alkylating agent- nitrogen mustard -Non-preferred option in chronic leukemias -FL- historical tx

Answer 123

Alkylating agent- nitrogen mustard -FDA discontinued manufacture of IV form d/t low demand -there is a topical form for cutaneous T cell lymphoma

Answer 124

Alkylating agent- alkyl sulfonate

Answer 125

Anti tumor antibiotic, alkylating agent-ethylene imine Do not use if crcl<30 or scr>1.7

Answer 126

Alkylating agent-ethylene imine

Answer 127

-great for delayed n/v ppx and TREATMENT -transient increase in wbc d/t demarginalization (also causes immune suppression) -antipyretic-masks fever -lymphocytic -decreases gut and brain edema -get bx before giving dex for suspected PCNSL (lymphocytic and can cause false negative) -spinal cord compression: 4 mg IV q6 -use 12 mg instead of 20 mg if with aprepitant/fosaprepitant -iv push: perineal burning -eye drops for HD-Cytarabine -for Pemetrexed rash -myopathy/muscle weakness -thrush -energy/euphoria -agitation/psychosis -gi ulcers -hyperglycemia -HTN -caution in n/v for brain tumors bc it decreases BBB inflammation and increases BBB integrity which decreases chemo exposure -Used in lymphomas (WM- DHAP, MCL- hyperCVAD) -MM

Answer 128

More with ***p***aclitaxel -***p***eripheral neuropathy -more lipophilic (hard to get onto solution) More with docetaxel -neutropenia -mucositis -docetaxel is stronger Both: -nail changes -full body alopecia -neuropathy is reversible

Answer 129

ALL Not myelosuppressive ADRs: hypersensitivity (can be allergic or non-allergic (d/t ammonia from asparagine breakdown) -allergic: usually not first dose. Don’t just increase premeds- drug isn’t working if real allergic rxn. Check activity level and Switch to different bacteria (erwinia instead of ecoli) for ***grade 3+*** rxn -non-allergic: often first dose. Increase premeds hyperglycemia, Hypertriglyceridemia, hyperammonium, ***coagulopathy*** (clotting more and bleeding), ***hepatotoxicity*** often transient, ***pancreatitis*** Want enzyme activity level to be ***at least*** 0.1 units/mL on day 7 MOA: depletes asparaginase in blood (normal cells can make their own but CA cells need to import it from outside the cell) ***Note: Do NOT switch to erwinia for ADRs! Only switch for inactivation or grade 3+ rxn*** (ADRs also often worse with erwinia) ***In adults cap long acting doses at 3750 units*** Peg q2wks Cal q3wks -Monitor fibrinogen twice weekly (FFP/cryo if <50-70) -lactulose/metronidazole/rifaximin for ammonioum but generally abates with time -hepatotoxicity-if t. Bili> 3, hold until bili<2

Answer 130

Immunosuppressant MDS- Aplastic anemia -infusion rxns -serum sickness

Answer 131

MDS, AML Hypomethylating agent Oral form should not be substituted where IV/SQ is used -IV/SQ for MDS and low intensity AML tx -***PO for AML maintenance ONLY!*** (int/poor risk who can’t get allo HCT) Take oral with antiemetic for ***at least first 2 cycles*** ***renally cleared- use decitabine instead of renal impairment*** Oral has poor bioavailability (~10%)

Answer 132

MDS ***NOT AML!!!*** Cytosine deaminase inhibitor/hypomethylating agent ***Oral***

Answer 133

MDS- aplastic anemia Calcineurin inhibitor

Answer 134

MDS, AML Hypomethylating agent -IV (but the PO combination product can be used in MDS as well) -NO SubQ for like azacitadine ***use instead of azacitadine if ESRD***

Answer 135

MDS- for iron overload Chelating agent Oral ****CI in high risk MDS*** d/t ADRs: liver/kidney damage and GI bleeding ***don’t use if crcl<40 (like deferoxamine)***

Answer 136

MDS- Second line for iron overload Chelating agent Oral Can cause agranulocytosis- so ***use is controversial unlike others***

Answer 137

MDS- for iron overload Chelating agent IM/SQ ***Avoid in crcl<40 (like deferasirox)*** Eye, ear, pulmonary toxicity

Answer 138

MDS- for thrombocytopenia if blasts are low, also for aplastic anemia Thrombopoetin agonist Oral Role unclear in MDS- c/f dx transformation and narrow fibrosis. Consider if severe or refractory thrombocytopenia

Answer 139

-MDS- del5q (consider first BEFORE epo level)- ***Unless ch 7 abnormality*** -R/R DLBCL -indolent lymphomas (FL, MCL) -MM Immune modulating agent REMs: pt (even men), MD, pharmacy ADR: fetal embryo toxicity (***even men***), ***thrombotic events*** may need ppx of Asa or AC-use saved score), hepatotoxicity, cutaneous rxns, ***TLS,*** tumor flare, decreased ability to mobilize for HCT w/ >4 cycles for MM, thyroid issues, ***diarrhea*** (use ***bile acid sequestrant***), skin hyperpigmentation (black pts), dermatological rxns (***rash***), peripheral neuropathy, -secondary malignancies!! -with or without food MM -tx 25 mg QD -maintenance: 10 mg daily -dose reduce for renal impairment -crcl 30-60: 10 mg/d -crcl <30: 15 mg QOD -HD: 5 mg QD ***should be able to use if crcl >30***

Answer 140

MOA: IgG1, TGF-B, smad 2/3 signaling MDS- ring sideroblasts (15%+ or 5%+ if SF3B1 mutation) Activin receptor ligand trap Helps w/ anemia but doesn’t modify the disease course SubQ injection ***hypertension- monitor before giving*** Thromboembolic events If inadequate response after 2 cycles (6 weeks) increase the dose (2 increases and if still no response then d/c) If Hgb 11.5+ in absence of transfusion- HOLD If inc of 2 within 3 weeks in absence of transfusion- dose reduce

Answer 141

Can be used in MDS Note: always start filgrastim within 72hs

Answer 142

Thrombopoetin agonist MDS- thrombocytopenia if blasts are low, more commonly used in ITP SQ Role unclear in MDS- c/f dx transformation and narrow fibrosis. Consider if severe or refractory thrombocytopenia ***Seem to be choice over eltrombopag for thrombocytopenia*** Goals plt 100-150k 2 mcg/kg

Answer 143

AML FLT3 inhibitor FLT3***-ITD/TKD*** mutation in de novo AML ADRs: ***pulmonary toxicity,*** cardiac issues, anemia, nausea Daily premedications for nausea and air out capsules (bad taste/smell) Severe 3A4 interaction- avoid w/ Azoles

Answer 144

AML FLT3 inhibitor FLT3-***ITD only*** mutation in de novo AML Serious ADRs: ***cardiac toxicity/arrhythmia (EKG)***, CNS (seizures, confusion), prolonged myelosuppression, higher incidence of early death (first 30 days) REMS!! 3A4 substrate

Answer 145

AML ***FLT3 inhibitor*** FLT3-***ITD or TKD*** mutation in ***relapse or refractory AML*** Serious ADRs: differentiation syndrome, arrhythmia (EKG), liver, fever, PRES, myalgia/arthralgias , orthostatic hypotension, inc cpk , pancreatitis, cytopenias Long half life

Answer 146

IDH1 inhibitor Relapsed/refractory AML with IDH1 mutation Serious ADR: differentiation syndrome, hepatotoxicity -empty stomach- otherwise absorption is increased and you get ADRs (like QTc-unlike at normal doses) ***-3A4 inducer*** -twice daily- unlike ivosidenib For differentiation syndrome you need to definitely hold even for less severe symptoms unlike other agents

Answer 147

IDH2 inhibitor De novo or relapsed refractory AML with IDH2 mutation Serious ADR: differentiation syndrome, can produce Gilbert’s like indirect hyperbilirubinemia, cytopenias, high WBC, pulmonary and/or renal dysfunction

Answer 148

BCL-2 inhibitor -AML- 28 day courses -but get marrow at d21-28 and give 7-14 day break if no dx -CLL- 1st line -R/R indolent lymphomas (MCL, WM) -R/R MM- with dex if t(11;14)- dose is higher (800 mg and no ramp up) ADRs: ***GI toxicity***, PNA, ***TLS (do ramp up),*** serious infxns, ***cytopenias*** -***DI with azoles! Must dose reduce venetoclax to 70 mg***- in AML stop azole when remission attained -other DIs: carvedilol (50% dec), digoxin (give dig ***6 hrs prior) -PO only -take ***WITH Food!*** affects Absorption ***Note: re-ramp up may be needed if interrupted for >1 week*** CLL weekly ramp up: 20, 50, 100, 200, 400 mg AML can consider 3 day ramp up ***purpose of ramp up is to decrease TLS risk***

Answer 149

Hedgehog pathway inhibitor ***AML- unfit for intensive therapy- give with LDAC*** -need to take birth control! -cardio toxicity/QTc -nausea, dysgeusia

Answer 150

APL adr: differentiation syndrome, ***dry skin***, LFTs, ***hypertriglyceridemia***, pseudotumor cerebri (increases ICP, give acetazolamide), myositis- give steroid Induces differentiation of APL cells PO only (can put in suspension if intubated)

Answer 151

APL Serious adr: differentiation syndrome, LFTs, QTc (monitor twice weekly) Supplement with k+ and mg+ during tx MOA: DNA fragmentation —>apoptosis -also degrades fusion protein PML (promyelocytic leukemia)-retinoids receptor alpha) *use freimingham or fredericka -QTc- stop for >450 mg (men) or 460 mg (women) -it’s ok to use with zofran -***headache***- extend infusion duration

Answer 152

ALL Use only in severe hypersensitivity (grade 3) or antibody inactivation to Peg-asparginase

Answer 153

CAR-T therapy: Anti-CD19 Relapsed/ refractory B-cell precursor ALL or R/R mantle cell lymphoma ***(third line after BTK-I)*** Risk for CRS and ICANS Pts shouldn’t drive x8 weeks after infusion

Answer 154

ALL Longer half life than peg Asparginase but minimal data in adults and AYA so use with caution Hydrolysis asparagine (normal cells can make but leukemia cells cannot) Cap dose in adults No more than q3wks

Answer 155

Antimetabolite (purine analog) AML, hairy cell leukemia, WM

Answer 156

Antimetabolite (purine analog) AML, ALL

Answer 157

Antimetabolite (pyramidine analog) Cell cycle specific AML, ALL, NHL ADRs: -cerebellar toxicity (increased risk with renal impairment, females, and elderly)- ***THIS IS FOR HIGH DOSE ONLY (1000 mg/m2+)***- DISCONTINUE! -conjuctivitis/keratoconjunctivitis (water soluble)- pre-tx (and continue for a few days after) w/ steroid eye drops (lubricating drops,dex + nsaid gtts)- ok to rechallenge. ***(This is also from HD-Cytarabine)***- TRUE -Ara-C syndrome: give steroids -avoid if renal failure! -***diarrhea*** Pearls: -metabolized by cytidine deaminase- which is everywhere- happens FAST- why we give it continuously otherwise metabolized to ara-U -rate limiting step in conversion is ***deoxy-cytidine-kinase***-this can be saturated at higher doses (debate about high doses)- after saturation the rest is metabolized to ara-U -ara-U is responsible to cerebellar toxicity (why it’s seen with high dose but not standard dose) -liposomal form for IT -HIDAC 3000 mg/m2 over 3 hr q12 hr x6 doses (on day 1, 3, and 5) -DLT- myelosuppression In FLAG-IDA Fludarabine upregulates deoxycytidine kinase which converts Cytarabine to its active form. Also G-CSF is used for priming here

Answer 158

BCR-ABL TKI- gen 2 ALL, CML chronic phase first line ADR: pleural effusion (risk does NOT decrease over time-could use diuretics), ***PAH*** (d/c therapy), myelosuppression, QTc!!, ***PLT inhibition*** Better BBB penetration -preferred in lymphoid variant blast phase ***contraindicated in V299L mutation*** -3A4 substrate

Answer 159

Anthracycline AML, ALL Red urine Cardiotoxicity seen at 550 mg/m2

Answer 160

AML- CPX351 ***this is a LIPOSOMAL product*** so for secondary AML -higher rates of ***prolonged thrombocytopenia and neutropenia*** (but lower rates of serious infxn- maybe protective of microbiota) -hemorrhage -copper overload

Answer 161

Steroids are part of backbone of tx in ALL- has anti leukemic activity

Answer 162

Antimetabolite (purine analog) -AML, CLL 1st line with cyclophos and/or rituximab -indolent lymphomas (WM, FL) Dose reduce for crcl<80 Could cause autoimmune hemolytic anemia- stop drug if occurs

Answer 163

Antibody drug conjugate - anti-CD33, calicheamicin (alkylation?) AML- if core binding fx: inv (16), t(16;16), t(8;21) (***don’t need CD33+ listed***) Risk of venoocclusive dx-permanently d/c, infusion rxn (give premeds)

Answer 164

AML, ALL Used to reduced WBC (>50-100k) when acute leukemia is suspected (cytoreduction)-generally prior to confirmation of subtype Also for chronic leukemias Goal is to decrease complications associated with leukostasis (pulmonary and neurological, stroke)

Answer 165

Anthracycline AML Many “theoretical” advantages over daunorubicin (uptake, potency, etc.) but not proven to be better Red urine

Answer 166

BCR-ABL TKI- gen 1 ALL, CML (1st line chronic phase), melanoma Minor: Diarrhea-self limiting, rash, arthralgia, periorbital edema, fatigue Severe: myelosuppression- transient, hepatotoxicity, worsening hypothyroidism, mild anemia, fetal embryo toxicity (men can still conceive), bone formation. Expensive With food and large glass of water -3A4 substrate -3A4 and 2D6 inhibitor (like nilotinib)

Answer 167

Antibody drug conjugate (anti-***CD22)***, calicheamicin (alkylation?) R/R- ALL ***Black box warnings*** -Veno-occlusive dx -higher post HSCT non-relapse mortality -better than blinatumomab with higher dx burden

Answer 168

Antimetabolite (purine analog) ALL maintenance daily (goal ANC 500-1500)- dose adjust in alternative fashion with MTX by 25% for out of range ANC Aka 6-MP ***Must dose reduce 50-90% if given with allopurinol*** Same time every day with or without food Increased serum lvls in hepatic impairment

Answer 169

Antimetabolite (purine analog) ALL- good for R/R ***T-cell*** ALL Neurotoxicity

Answer 170

ALL Hydrolyses asparagine (leukemic cells cannot make) Cap at 3750 units in adults No more than q2wks

Answer 171

Biological response modulator (anti-CD123) Indication: blastic plasmacytoid dendritic cell neoplasm (BPDCN) Warning: capillary leak syndrome

Answer 172

Antimetabolite (purine analog) ALL -sinosoidal obstructive syndrome: may need allopurinol (plus dose modification) if skewed metabolism- but ***dose reduce 50-75%*** since they interact Allopurinol shift metabolism from hepatotoxic and ineffective metabolite 6-MMP to 6TGN

Answer 173

Car-T cell therapy CD-19 Adults with relapsed/refractory B-cell NHL or R/R follicular lymphoma, R/R MZL REMS Pts should not drive x8 weeks after infusion ICANS-worse than other CAR-T

Answer 174

CAR-T cell therapy CD19 Relapsed refractory B-cell NHL

Answer 175

CAR-T cell therapy targeting BCMA Relapsed/ refractory multiple myeloma ADR: ***Parkinsonism*** Lymphodeplete with cyclophos and Fludarabine for 3 days, then start 2-4 days later Premed with APAP and diphen but ***NOT dex*** (decreased efficacy)

Answer 176

BTK inhibitor CLL- 1st line, R/R MCL- R/R ADR: ***headache*** (occurs early and resolves in 4-8wks) Low incidence of bleeding, HTN, and afib (so less ADRs than ibrutinib) -tablet form released which does NOT ***interact with PPI/H2***- capsule DOES interact- separate 2h before and after -3A4 substrate

Answer 177

Anti-CD52 mAb Chronic leukemia via compassionate use program

Answer 178

BCR-ABL and STAMP TKI Chronic phase CML with: -T315I mutation OR -resistance or intolerance to 2 prior TKIs Dose: -40 mg BID or 80 mg QD -T315I mutation- 200 mg BID -3A4 and 2C9 substrate ***Does NOT prolong QTc- only one that doesnt***

Answer 179

BCR-ABL TKI- gen 2 CML- chronic phase 1st line Bone marrow suppression, ***diarrhea/GI issues*** ***contraindicated in V299L mutation*** With food and large glass of water -3A4 substrate

Answer 180

P13K inhibitor CLL- R/R after 2 prior lines of therapy Black box: infection, diarrhea/colitis, cutaneous rxns, pneumonitis -Cyp3A4 substrate -with or without food

Answer 181

BTK inhibitor -CLL- 1st line -R/R DLBCL (non-germinal center) -indolent lymphomas (WM, MZL, R/R MCL) ADR: bleeding, afib (***don’t hold unless grade 3+***), HTN -arthralgia, diarrhea -***NO warfarin***- use alternative AC (Apixaban preffered) -3A4 substrate

Answer 182

P13K Inhibitor CLL- relapsed, in combo with rituximab Hepatotoxicity, diarrhea, hematological -cyp3A4 substrate AND inhibitor (unlike duvelisib which is just a substrate) -with or without food

Answer 183

BCR-ABL TKI- gen 2 CML- 1st line chronic phase) ADR: ***QTc!!!-BLACK BOX*** GI and liver toxicity, peripheral arterial occlusive dx, metabolic syndrome, pancreatitis (like Ponatinib) Empty stomach ***Only one that is twice daily- so not good option if adherence is bad!!*** ***Ok in V299L mutation*** -3A4 substrate -3A4 and 2D6 inhibitor (like imatinib)

Answer 184

Anti-CD20 mAb -Chronic leukemias -FL Could split 1st dose over 2 days on CLL to decrease infusion rxn

Answer 185

Anti-CD20 mAb Chronic leukemias CLL? Exclusively available via patient access Novartis oncology program (PANO)

Answer 186

Cephalotaxine; protein synthesis inhibitor CML: -chronic phase OR -pts ***who PROGRESS to accelerated phase (not for de novo- don’t get tripped up)*** *for resistant or intolerant to 2 TKIs* SubQ BID-ouch! ***Hyperglycemia***

Answer 187

Adenosine deaminase (ADA) inhibitor Hairy cell leukemia- one of the preferred initial options

Answer 188

BTK inhibitor -CLL -R/R -MCL- R/R after 2+ lines of therapy including BTK-I Novel mechanism (***non***-covalent binding)- allows it to work in patients that progressed in prior BTK-I -ADR: bleeding, afib, ***cytopenias*** -3A4 substrate, increases digoxin (pgp)

Answer 189

BCR-ABL TKI ALL CML- chronic phase with: -T315I mutation ***drug of choice***- 45 mg but decrease to 15 mg when bcr-abl <1% -resistance or intolerance to 2 TKIs Risk for ***arterial thromboembolic events*** (it has pan-VegF inhibition), pancreatitis, HF, hepatotoxicity Obtain via Takeda oncology Here2Assist program -3A4 substrate

Answer 190

BTK inhibitor -CLL- category 1 preferred for second line and subsequent therapy with or without del(17p)/TP53 mutation -R/R MCL -First line WN -second line MZL ADR: ***myelosuppression, PNA, upper respiratory tract infxns,*** cytopenias -low incidence of bleeding, HTN, and afib (like Acalabrutinib) -3A4 substrate -160 BID or 320 daily

Answer 191

Bispecific t-cell engager Brings two antibodies together- one side targets t-cell and the other targets the antigen - then T cell kills antigen Bypasses need to co-stimulation Usually tried after CAR-T therapy Off the shelf- no crazy manufacturing like CAR-T

Answer 192

R/R hairy cell leukemia after 2+ systemic therapies including purine analogs Anti-CD22 mAb conjugated to PSA endotoxin ADR: infusion rxns, capillary leak syndrome, hemolytic uremic syndrome Give ASA in d1-8 of each cycle Product provided as two separate vials- so be careful when making! Drug no longer available for ***new starts*** after 7/2023

Answer 193

Antibody drug conjugate -CD30 Hodgkin’s lymphoma

Answer 194

Bispecific antibody- CD20/CD3 R/R DLBCL- third line ***R/R follicular lymphoma- third line*** -Step up dosing -SubQ -hospitalize x24h following first dose of 48 mg (full dose) -premed: steroid, diphen, APAP for ***cycle 1*** -premed with steroid for all cycles -continue steroid x3 days following each dose -CRS, ICANS -nausea , diarrhea, pyrexia, MSK pain, abdominal pain, serious infxns

Answer 195

Bispecific antibody- CD20/CD3 R/R DLBCL- third line -Step up dosing -MUST get pretreatment dose of ***obinituzumab*** 7 days prior to first dose -max 12 cycles ***(this is finite unlike epcoritimab)*** -premeds: steroid, diphen, APAP for ***first 3 cycles*** -APAP and antihistamine in all subsequent cycles -CRS, ICANS -serious infection, tumor flare, MSK pain, rash, fatigue -hospitalization required for the first 2.5 mg step up dose

Answer 196

Antibody drug conjugate -CD19 directed antibody with ***alkylating*** agent conjugate (SG3199) R/R DLBCL (2+ prior tx)-third line -Premeditate with dex 4 mg bid x3 days beginning day before -dex is used to mitigate ***edema*** because ***LOOP DIURETICS WONT HELP WITH EDEMA*** (try spironolactone) Other: -photosensitivity -infection -extravasation -serious rash

Answer 197

Antibody drug conjugate -***CD79B*** -MMAE (antimicrotubule) R/R DLBCL: PBR regimen ADR: ***thombocytopenia***, peripheral neuropathy, infusion rxns (90 minute observation and premed), FN (consider G-CSF), opportunistic infections (***HSV/PJP ppx),*** PML, TLS, hepatotoxicity, PNA 3A4 interactions d/t vedotin!!

Answer 198

Used in DLBCL, PMBL, BL, HL, indolent lymphomas, MM

Answer 199

Anti-CE 19 mAb R/R DLBCL ineligible for auto HCT; tafasitamab w/ Lenalidomide

Answer 200

Selective inhibitor of Nuclear export (SINE) MM, 3rd line DLBCL ADRs: hyponatremia, neurotoxicity, GI toxicity (diarrhea ~14 days in) hemorrhagic events, N/V -use dual antiemetic ppx (5HT3 + NK-1/OLZ) -tablets- with or without food

Answer 201

SubQ CLL, DLBCL, FL: all have different administration times and vial sizes Must have tolerated at least one full dose of IV

Answer 202

R/R cutaneous T-cell lymphoma after at least ***one*** prior therapy Selectively binds to CCR4 -worsens autoimmune mediated things like any autoimmune disorder or GVHD- so caution in these patients! -rash -infections -infusion rnxs

Answer 203

Radiotherapy Follicular lymphoma

Answer 204

Proteosome inhibitor -MM -WM -Can be inactivated by high intake of vitamin C -peripheral neuropathy (IV>SQ) (usually within 1st 5 cycles it starts) -reactivation of HSV/VZV- need ppx -minimum 72h b/w doses -blepharitis- tx w/ ketotifen or doxycycline -thrombocytopenia, hypotension, TMA -***weekly*** preferred for MM tx Dose adjust in hepatic impairment Rare hearing loss

Answer 205

Proteosome inhibitor WM, MM ADR: ***cardiac and pulmonary toxicity*** and renal -***Screen for hep b*** -HSV/HSV ppx -Infusion rxn- premeditate w dex (can be immediate or delayed) -hydration- decrease TLS and AKI -slower rate decreases cardiopulmonary tox -need VTE ppx if given w/ dex! -max BSA 2.2 to calculate dose -once weekly may be ok -watch: EF, BP, electrolytes, liver and renal function, thrombocytopenia, TMA, TTP, HUS, PRES, inc tox w/ Melphalan -***much less neuropathy*** -IV not SQ -hydration before 1st cycle (TLS) Dose adjust in hepatic impairment

Answer 206

P13K inhibitor ***withdrawn from US market*** IV

Answer 207

Bispecific antibody - CD20/CD3 FL- R/R after 2+ lines of therapy -step up dosing -q21 days x8 cycles (up to 17 cycles of only PR) -premeds: steroid, APAP, h1 blocker (***for cycle 1 and 2, optional beyond that*** -hospitalization for monitoring is NOT required -CRS -neurologic toxicity -fatigue, rash, pyrexia, HA, Dec lymphocytes and myelosuppression ***Infections!! Consider PJP and HSV ppx***

Answer 208

Relugolix is oral

Answer 209

Antiandrogens, less commonly used that bicalutamide d/t tolerability Flutamide: ***diarrhea,*** hematuria, give with LHRH agonist, most hepatotoxic Nilutamide: diarrhea, disulfiram like rxn ***avoid if etoh drinker***, visual issues, interstitial PNA, give with orchiectomy ***hot flashes are common***

Answer 210

Darolutamide: prostate Daratumumab: MM Durvalumab: bladder second line

Answer 211

Antibody drug conjugate Targets BCMA Removed from market- available for Compassion use only for relapsed refractory ***multiple myeloma*** Infusion rxns, ocular toxicity (lubricating eye drops), thrombocytopenia REMs Need eye exam before each infusion, need lubricant eye drops, avoid contact lenses

Answer 212

Human IgG1k mAb target ring CD38 -***HSV/VSV ppx*** during tx and for ***3 months after*** -Upper respiratory tract infections -***screen for hep B*** -infusion rnxs (more with IV than SQ, more with faster infusions) -could split 1st dose over 2 days to reduce infusion rxn -premeds with APAP, dex, diphen (may omit for SQ staring with 4th dose) -could use ***montelukast*** to decrease infusion rxn -different volumes for doses 1 v 2 v 3 -SQ is flat dose -don’t need IV test dose like rituxan -abdomen over 3-5 mins -can interfere with blood type and screening -after 2 tolerated doses you can do rapid administration over 90 mins

Answer 213

Humanized IgG1 mAb that targets SLAMF7 protein Multiple myeloma -NOT given alone (usually with IMID) -after 1-3 failed therapies (sooner than car-t and BiTEs) -GI toxicity -infusion rxns- premed with dex, diphen, APAP, H2 Options: -elo + Len + dex -elo + Pom + dex -elo + bor + dex

Answer 214

Bispecific antibody, BCMA, CD3 R/R MM- at least 4 prior lines of therapy including PI, immunomodulatory agent, and Anti CD38 Step up dosing (like teclistimab), hospitalize and monitor x48 and 24h for doses 1 and 4 respectively Premeditate with dex, APAP, and diphen ***before step up doses (prevents CRS)*** REMs for CRS and ICANS ***Given alone*** (like teclistimab and talquetamab, unlike elotuzumab) ***Infections!! Consider PJP and HSV ppx***

Answer 215

CAR-T targeting BCMA MM Lymphodeplete with cyclophos and Fludarabine for 3 days, then start 2 days later Premed with APAP and diphen but ***NOT dex*** (decreased efficacy)

Answer 216

Chimeric IgG1 mAb that binds CD38 R/R MM -HSV/VZV ppx during tx and for 3 months after -premeds for infusion rxn -***hep B screening*** -can interfere w/ blood typing -infusion rxns -upper respiratory tract infections -diarrhea

Answer 217

Proteosome inhibitor MM -HSV/VZV ppx -ADRs: ***GI toxicity (N/V/D),*** fluid retention, dermatological toxicity, peripheral neuropathy (less than velcade) -oral- capsules -take on Empty stomach- 2hr after or 1 he before a meal with a glass of water

Answer 218

Immunomodulating agent MM ADR: dermatological toxicity, ***myelosuppression,*** VTE (ppx) (Less diarrhea and rash than revlimid) REMS- teratogen

Answer 219

Bispecific GPRC5D directed CD3 t-cell engager R/R MM- at least 4 prior therapies including PI, immunomodulatory agent, anti-CD38 Step up dosing for CRS- hospitalized x48h after each step up Premeds with dex, APAP, diphen ***(CRS PPX)*** REMs for CRS and ICANS ***skin and nail toxicity*** ***taste changes*** and weight loss ***Given alone*** (like teclistimab and elrantamab , unlike elotuzumab) Infections- not quite as bad as BCMAs

Answer 220

Bispecific antibody- BCMA and CD3 R/R MM- 4+ prior therapies including PI, immunomodulatory agent, anti- CD38 mAb ***CRS ppx: dex + APAP + diphenhydramine*** (PREVENTS CRS) ADR: infections (***acyclovir***, often pjp ppx too), CRS, neurotoxicity Step up dosing and hospitalization x48h after each dose increase REMs- CRS/neurotoxicity (ICANS) ***Given alone*** (like elrantamab and talquetamab, unlike elotuzumab) Approved for new technology add on payment for limited time ***Infections!! Consider PJP and HSV ppx***

Answer 221

Immunomodulatory agent MM ADR: constipation, peripheral neuropathy, neurotoxicity (sedation), VTE (give ppx) REMs- teratogen -Capsules- empty stomach at bedtime -does not require week off like Lenalidomide and pomalidomide -***no renal*** or hepatic adjustments

Answer 222

Hypercalcemia of malignancy 4-8 units/kg q6-12hr ***IM or SQ*** Onset: 2-4 hrs Tachyplylaxis- limit to ***48h max*** ***nasal form is NOT effective*** Not used alone!! ***avoid if fish allergy*** Probably for more severe cases (ca2+ >14)

Answer 223

-Start within 6 hours -remove cold packs for at least 15 minutes before, and during tx -iron chelator that works by preventing formation of free radicals which inhibits necrosis Testicular atrophy and infertility

Answer 224

IL-2 Melanoma Not used much d/t toxicity and low response Capillary leak syndrome

Answer 225

MEK inhibitor Melanoma, NSCLC Ocular toxicity, decrease LVEF

Answer 226

MEK inhibitor Melanoma (with vemurafenib) Highest rates of ADRs of all BRAF/MEK inhibitors: rash, transaminitis, may decreased LVEF

Answer 227

BRAF inhibitor Melanoma, ovarian, thyroid, NSCLC, HCC ADRs: fever, chills, flu-like symptoms, QTc, hand/foot syndrome, ocular toxicity -empty stomach -DDIs: clarithromycin, estrogens/progestins -hyperglycemia -alopecia -arthralgias -fever- antipyretics, steroids, maybe dose reduction

Answer 228

PD-1 inhibitor + lymphocyte activation gene-3 (LAG3) blocking antibody Melanoma Relatlimab only available in this combination

Answer 229

Oncolytic virus Melanoma- unresectable ***stage III***, satellite or in transit lesion Local injection site rxns -caution: viral transmission: -blood may be infectious -urine is infections day of inj -avoid contact w/ tx site -wear gloves, keep covered x 1 wk -dispose of stuff in sealed plastic bag -keep covered x1 week -wash hands -avoid acyclovir and antiherpetics -intralesional injection -fever, chills, fatigue, cellulitis

Answer 230

gp100 targeted Bispecific T cell engager Melanoma- HLA-A*02:01 pts only - I believe this is uveal melanoma ADRs: ***itching/rash*** (give topical steroid, antihistamine, and maybe oral steroid), ***CRS*** First BiTE for solid tumor ***First 3 doses*** require observation for ***16 hours***

Answer 231

BRAF inhibitor Highest rate of AES of all BRAF/MEK combos: rash, transaminitis, QTc Melanoma (with Cobimetinib)

Answer 232

MEK inhibitor Ovarian, Melanoma, thyroid, NSCLC-MEK, HCC ADR: may decrease LVEF, dermatological toxicity (rash), fevers, ocular toxicity, anemia -empty stomach -Refrigerate

Answer 233

Nk1 blocker Not an inhibitor of cyp3a4 Does inhibit bcrp- watch mtx, mitoxantrone, imatinib, lapatinib, gefitinib, topotecan, irinotecan Oral Iv removed from marker for hypersensitivity rxns Long half life 130hr- only one dose needed

Answer 234

GM-CSF Stimulates granulocytes and macrophages -Primarily for HCT -also indicated in AML

Answer 235

Long acting G-CSF

Answer 236

EGFR inhibitor -Head/neck -colorectal (KRAS wildtype) -***Rash, acneform rash***, skin/hair/nail toxicity, ***diarrhea,*** low mg -Hypersensitivity- this is IgE (inc risk in southeast US, more than with panitumumab d/t chimeric structure opposed to humanized)- Need ***Benadryl*** premed. Usually fast it 1st or 2nd cycle. Switch to panitumumab!! -check alpha gal IgE (don’t tx if positive)-from lone star tick bite, or develops antibodies! (this is a true anaphylactic rxn!!) -hypomagnesemia!!! -***rare aseptic meningitis***

Answer 237

PD-1 inhibitor Metastatic/recurrent nasopharyngeal carcinoma (with cisplatin/Gemcitabine)- or single agent if progression on platinum

Answer 238

RET kinase inhibitor, also VEGF Thyroid, NSCLC- RET ADRs: interstitial lung dx, HTN, hemorrhagic events, liver toxicity, wound healing impairment, HTN, edema, TLS, bone marrow suppression, electrolyte abnormalities, increased CK, edema, ***hypothyroidism*** -empty stomach -many 3A4 interactions

Answer 239

Multi kinase inhibitor (VEGF, EGFR, RET) Thyroid- mainly MTC ADR: cardiotoxicity, HTN, HF, dermatological toxicity, GI toxicity, bleeding risk, ***hypothyroidism*** -***REMS:*** d/t QTc risk -obtain k, ca2+, mg, TSH, and ecg before initiation and regularly throughout tx

Answer 240

Mucositis prevention in RT Not approved in United States

Answer 241

Papillary and follicular thyroid cancer NOT for MTC or anaplastic -stop levoxyl and do iodine free diet beforehand -N/V -xerostomia -infertility (especially men) no preganancy x1 yr after- ***pregnancy test for all women regardless of sexual hx and birth control*** -no pregnancy or ***breastfeeding*** -risk of secondary cancer -there is a max lifetime dose -no contrast dye- blocks uptake of RAI -give with beta blocker or methimazole in ***elderly or cv risk pts***

Answer 242

Give in BC concurrently with WBRT and x6 months after to delay cognitive decline

Answer 243

KRAS inhibitor -NSCLC- KRAS G12C mutation after 1 prior line of therapy -biliary tract and pancreatic cancers (KRAS G12C mutated) -colorectal (KRAS G12C, usually with EGFR-I) ADRs: significant nausea, diarrhea, ***QTc prolongation*** Others: edema, hepatotoxicity, fatigue, decreased appetite, dyspnea, MSK pain, ILD Penetrates CNS 3A4 substrate (like sotorasib)- VERY POTENT!! Also cyp inhibitor!

Answer 244

EGFR inhibitor NSCLC-advanced/metastatic- preferred first line if ***EGFR S768I, L861Q, or G719x*** ADRs: rash, ***diarrhea,***, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD -empty stomach -renal dose adjustment

Answer 245

ALK inhibitor NSCLC- ALK ADRs: ***fatigue, constipation, edema, myalgia,*** visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD -with food -***anemia*** -weight gain

Answer 246

Bispecific antibody targeting: EGFR and MET inhibitor This is NOT BITE therapy! NSCLC- exon 20 insertion mutation NCCN preferred for 1L in combo with chemo Premeds: dex (***prior to wk 1 d1-2, then optional***), diphen, APAP- still everyone reacts!- can rechallenge on day 2 ADRs: ***Rash, paronychia***, MEK pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipatin, vomiting ***Give via peripheral line for first 2 cycles (infusion rxns), then can do central after that***

Answer 247

MET inhibitor NSCLC- MET exon 14 skipping mutation ADRs: ***edema*** (hallmark), ***photosensitivity***, hematologic toxicity, inc scr, ***significant nausea***, ILD, hepatotoxicity, elevated amylase/lipase -bottle only good for 6 weeks after opening -DDI: 3A4 (major substrate- tepotinib is minor), PPI (unlike tepotinib) -BID (shorter half life) -likely has CNS penetration

Answer 248

PD-1 inhibitor -NSCLC- first line locally advanced or metastatic dx with PD-L1 50%+, also in combo with chemo for 1L (no PD-L1 requirement) -locally advanced basal cell carcinoma after hedgehogs pathway inhibitor (sonidegib) or if hedgehog inhibitor is not appropriate -SCC (skin cancer): locally advanced or metastatic not candidates for surgery or RT

Answer 249

ALk inhibitor, ROS1 ADRs: ***fatigue, constipation, edema, myalgia,*** visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD -450 mg ***WITH FOOD*** -moderately emetogenic -more GI ADRs -CNS penetration -

Answer 250

EGFR inhibitor NSCLC- EGFR ADRs: rash, ***diarrhea,***, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD -more toxicity compared to others -DDI: PPI/H2

Answer 251

BRAF inhibitor -NSCLC- BRAFV600E (with binimetinib) -colorectal (BRAFV600E- in combo with cetuximab or panitumumab) Specific guidelines for dose reductions with CYP3A4 inhibitors

Answer 252

EGFR inhibitor -NSCLC-EGFR- -can be combined with bevacizumab or ramucirumab (unlike others) -pancreatic (not used in clinical practice) ADRs: rash, ***diarrhea,***, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD -increased AC with warfarin -DDI: PPI/H2 -inc clearance with smoking -empty stomach

Answer 253

EGFR inhibitor NSCLC- EGFR ADRs: rash, ***diarrhea,***, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD -increases AC with warfarin -more diarrhea -mail changes

Answer 254

Alkylating agent ***SCLC***- subsequent lines- ***IF NO BRAIN METS!!!** Very well tolerated despite PI highlighting hepatotoxicity and myelosuppression -vesicant!! -respiratory and GI -rhabdo: watch scr and CPK

Answer 255

EGFR- inhibitor NSCLC- ***squamous*** (in combination with gem-cis) Removed from NCCN guidelines

Answer 256

EGFR inhibitor NSCLC- EGFR ***exon 19 deletion or exon 21 L858R*** -IB-IIIA ***COMPLETELY RESECTED*** (negative margins) who received prior adjuvant chemo -advanced/metastatic: first line- preferred over others -advanced/metastatic: second line if T790M and not already used ADRs: rash, ***diarrhea,***, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD -Less ADRs than others overall -increases QTc -decrease LVEF -***high CNS penetration*** -hematologic toxicity (transient decrease in plts) -increased pneumonitis if given after ICI

Answer 257

VEGF inhibitor -NSCLC -HCC: AFP >400 and child Pugh A only -gastric/esophageal- second line ***adeno only*** -colorectal (less data than bevacizumab) Considerations: -high risk VTE and upper GI bleed for pts with upper GI cancers -***HTN*** and ***Diarrhea***

Answer 258

KRAS inhibitor (RAS GTPase family inhibitor) -NSCLC- KRAS G12C mutation- locally advanced or metastatic after 1+ line of prior therapy -colorectal (off label, KRASG12C, give with EGFR-I if able) ADRs: ***hepatotoxicity***, diarrhea, inc urine protein, hematologist toxicity, MSK pain, fatigue, ILD DDI: ***PPI/antacids,*** 3A4 substrate Also cyp inhibitor!

Answer 259

CTLA4 inhibitor -NSCLC- in combo with Durvalumab + chemo -unresectable HCC- in combo with Durvalumab

Answer 260

MET inhibitor NSCLC- MET exon 14 skipping mutation ADRs: ***edema*** (more than capmatinib and not responsive to diuretics), hypoalbuminemia, hematologic toxicity, hepatotoxicity, interstitial lung dx, elevated amylase/lipase -minor 3A4 substrate (capmatinib is major) -with food! (Unlike capmatinib) -daily (longer half life)

Answer 261

EGFR inhibitor NSCLC- EGFR exon 20 insertion mutation -oral (unlike amivantamab) ADRs: nausea, QTC, ILD, classic EGFR ADRs, edema, HF ***WITHDRAWN FROM MARKET***

Answer 262

Crizotinib and Cabozantinib We know capmatinib and tepotinib are

Answer 263

FGFR inhibitor Cholangiocarcinoma with FGFR2 fusion or rearrangement Hyperphosphatemia, ***eye disorders***

Answer 264

Topo-I inhibitor -Pancreatic with 5FU -Biliary tract cancer with 5FU Rates of diarrhea and myelosuppression are pretty similar to regular irinotecan, so no huge toxicity benefit Not a 1:1 dose conversion with conventional More expensive 70 mg/m2, but give 50 mg/m2 for homozygous ugt1A1*28

Answer 265

FGFR inhibitor Cholangiocarcinoma with FGFR2 fusion or rearrangement Hyperphosphatemia, ***eye disorders***

Answer 266

Antidote for 5FU and capecitabine (competes for intervention into RNA) Give within ***8-96 hours*** Interferes with RNA false base pair activity 1. Can use for catastrophic overdose (not just finishing a bit early) more for pump malfunction of capecitabine suicide attempt, or 2. immediately found to have DPD deficiency (severe ADR with ***FIRST*** exposure) Q6h for 20 doses (5 days)

Answer 267

Somatostatic analog Pancreatic cancer- used in PNET for symptom and tumor control

Answer 268

Somatostatin analog Pancreatic cancer- used in PNET for symptom and tumor control ***For chemo diarrhea*** -grade III-IV or persistent despite loperamide -100-150 mcg TID (up to 500 TID) or continuous infusion 25-50 mcg/hr -***wean off, don’t stop abruptly*** (biliary colic)

Answer 269

Antimetabolite (pyramidine analog)/thymidine phosphorylase inhibitor -gastric/esophageal- third line ***adeno only*** -colorectal (may use with bevacizumab) ADR: myelosuppression, fatigue Consider barriers to taking in a pt with upper GI cancer (crush-ability, absorption) Dose based on trifluridine component (round down) Need CBC on day 1 and 15 of each cycle (dose adjust based on neutrophil count)

Answer 270

Locally advanced or metastatic basal cell carcinoma that has recurred after surgery or is not a candidate for surgery or RT -taste changes, weight loss, muscle spasms, fatigue, GI Oral Check CK and scr

Answer 271

Hedgehog pathway inhibitor Locally advanced basal cell carcinoma that has recurred after surgery or is not a candidate for surgery or RT -taste changes, muscle spasms, inc CK, weight loss, fatigue, GI Oral Check ***CK and scr***

Answer 272

VEGF- TKI Colorectal cancer ***second line*** metastatic dx after fluoropyrimidine, Oxaliplatin, and irinotecan based chemo, and anti-VEGF therapy and and EGFR therapy ***(if RAS/RAFwildtype)*** -VEGF toxicities -increased triglycerides/cholesterol, thrombocytopenia, infections -more selective than regorafenib (and probably less toxicities)

Answer 273

EGFR inhibitor Colorectal cancer (only if KRAS wildtype) -Skin/hair/nail toxicities are most common especially ***acniform rash*** (less than with cetuximab- ***don’t need Benadryl)*** -***diarrhea*** -hypomagnesemia!! -paronychia, mucositis: ***both of these more than cetuximab***

Answer 274

VEGF inhibitor Colorectal cancer- only given with irinotecan based regimen ***Most people use bevacizumab for the VEGF, this is an option but is more expensive and there is less data)***

Answer 275

Cutaneous T-cell lymphoma His tone deacetylase inhibitor -GI (n/v/d), anemia, thrombocytopenia

Answer 276

Cutaneous T-cell lymphoma and peripheral T-cell lymphoma Histone deacetlyase inhibitor ***QTc prolongation***, -GI (n/v/d), anemia, thrombocytopenia Withdrawn from US market for PTCL but still somehow available for CTCL and listed in NCCN

Answer 277

Antimetabolite Peripheral T cell lymphoma and cutaneous T cell lymphoma Need b12 supplementation like pemtrexed For drug interactions think of one’s similar to MTX

Answer 278

Peripheral T cell lymphoma Histone deacetylase inhibitor Reduce dose if homozygous ugt1A1*28

Answer 279

“Other” regimen for subsequent line follicular lymphoma

Answer 280

Single dose G-CSF There should be at least 14 days between dose and next chemo cycle (unlike pegfilgrastim which is 12 days)

Answer 281

Reversal agent for ifosphamide neurotoxicity Adrs: seratonin syndrome, hemolysis

Answer 282

Reversal agent for ifosphamide neurotoxicity Adrs: seratonin syndrome, hemolysis

Answer 283

NSCLC- ROS-1 positive With or without food Good activity against G2032R and D2033N mutations in ROS1 Dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive d/o, MSK weakness Warnings: CNS effects (like lorlatinib), interstitial lung dx, hepatotoxicity, myalgia and CK elevation, hyperuricemia, fractures, embryo fetal tox 3A4 substrate AND inducer Pgp substrate

Answer 284

PD-L1 Second line: esophageal ***squamous cell***

Answer 285

Vedotin- MMAE, antimicrotubule Govetecan- SN38, topo-1 inhibitor Tesirine- SG3199, alkylating Ozogamicin- calichimichin, Dna breaks Deruxtecan- dxd/dx8951 (MAAA-1181a), topo-1 inhibitor Emtansine- DM1, antimicrotubule Soravtansine- DM4, antimicrotubule

Answer 286

Synovial sarcoma

Answer 287

Synovial sarcoma

Answer 288

Telomerase inhibitor Low risk MDS in pts who have lost response to or are ineligible for epo

Answer 289

VegF R/R colorectal

Answer 290

-Dara-VRD -Dara-KRD -Dara-VTD -Dara-CyBorD

Answer 291

Type-1: activity against ITD and TKD Type-2: Generally only activity against ITD

Answer 292

Type-1: activity against ITD and TKD Type-2: Generally only activity against ITD

Answer 293

Topo inhibitors: G2 and S Antimetabolites: S Antimicrotubules: M Bleomycin: G2 Hormonal drugs: G1 Asparaginase: G1 Dactinomycin: G1

Answer 294

Peptide receptor radioneucleotide therapy Kinda like antibody drug conjugate except payload is radiation Combines synthetic somatastatin dotatate with lutetium lu177 Don’t give with long acting somatostatin analog (octreotide LAR) since it has somatastatin analog- separate long acting by ***4 weeks*** Can use short acting octreotide but stop 24 hrs before dose It’s for NET Note NET found anywhere in body but most often pancreas, GIT, appendix, and lungs

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