Chemotherapy Flashcards

Question

trabectedin MOA

Answer 1

alkylating agent cell cycle non-specific - cells are most susceptible in G1/S

Answer 2

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 3

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 4

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase ACTIVATED in plasma via dephosphorylation

Answer 5

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 6

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase ACTIVATED by demethylation by adenosine deaminase to ara-G

Answer 7

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 8

antimetabolite > purine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 9

antimetabolite > pyrimidine analog > hypomethylating agent (DNA methyltransferase inhibitor) - disrupt nucleic acid production > apoptosis incorporated in DNA AND RNA cell cycle-specific > S-phase

Answer 10

antimetabolite > pyrimidine analog - disrupt nucleic acid production > apoptosis also inhibits thymidylate synthase (TS) cell cycle-specific > S-phase

Answer 11

antimetabolite > pyrimidine (cytidine) analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 12

antimetabolite > pyrimidine analog > hypomethylating agent (DNA methyltransferase inhibitor) - disrupt nucleic acid production > apoptosis ONLY incorporated in DNA cell cycle-specific > S-phase

Answer 13

antimetabolite > pyrimidine (cytidine) analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 14

antimetabolite > pyrimidine analog - disrupt nucleic acid production > apoptosis also inhibits thymidylate synthase (TS) - improved 5-FU efficacy when given with leucovorin - leucovorin is precursor of reduced folate cofactor that stabilizes binding to TS > prolonged enzyme inhibition vs 5-FU alone cell cycle-specific > S-phase

Answer 15

antimetabolite > pyrimidine analog - disrupt nucleic acid production > apoptosis cell cycle-specific > S-phase

Answer 16

antimetabolite > pyrimidine analog - disrupt nucleic acid production > apoptosis (with tipiracil) cell cycle-specific > S-phase

Answer 17

antimetabolite > antifolate - disrupt nucleic acid production > apoptosis inhibits dihydrofolate reductase (DHFR) - decr formation of reduced folates (tetrahydrofolate; THFR) - polyglutamate active metabolites, which inhibit folate-dependent enzymes of thymidylate and purine biosynthesis, are selectively retained in tumor cells - duration of cellular exposure is key to efficacy; also correlates with tox cell cycle-specific > S-phase

Answer 18

antimetabolite > antifolate - disrupt nucleic acid production > apoptosis inhibits dihydrofolate reductase (DHFR) and thymidylate synthase (TS) - decr formation of reduced folates (tetrahydrofolate; THFR) - polyglutamate active metabolites, which inhibit folate-dependent enzymes of thymidylate and purine biosynthesis, are selectively retained in tumor cells - duration of cellular exposure is key to efficacy; also correlates with tox cell cycle-specific > S-phase

Answer 19

antimetabolite > antifolate - disrupt nucleic acid production > apoptosis inhibits dihydrofolate reductase (DHFR) - decr formation of reduced folates (tetrahydrofolate; THFR) - polyglutamate active metabolites, which inhibit folate-dependent enzymes of thymidylate and purine biosynthesis, are selectively retained in tumor cells - duration of cellular exposure is key to efficacy; also correlates with tox cell cycle-specific > S-phase

Answer 20

enzyme inhibitor > topo I inhibitor > camptothecin topo I inhibition via formation of stable cleavable complexes --> interferes with DNA replication and formation of ssDNA breaks --> cell cycle arrest irinotecan = PRODRUG activated via carboxylesterases to potent active metabolite (SN-38) cell cycle-specific > S-phase

Answer 21

enzyme inhibitor > topo I inhibitor > camptothecin topo I inhibition via formation of stable cleavable complexes --> interferes with DNA replication and formation of ssDNA breaks --> cell cycle arrest cell cycle-specific > S-phase

Answer 22

enzyme inhibitor > topo II inhibitor > anthracycline > induce apoptosis from DNA damage and topo II inhibition > free radical formation, altered signal transduction DNA intercalation in nucleus - blocks DNA/RNA synthesis topo II inhibition forms drug–DNA–enzyme cleavable complex - prevents resealing of DNA breaks and leads to double-stranded breaks - inhibits ability of helicases from dissociating DNA into single strands, blocking DNA replication generation of semiquinone and oxygen free radicals cell cycle-specific > G1/S-phase

Answer 23

enzyme inhibitor > topo II inhibitor > anthracycline > induce apoptosis from DNA damage and topo II inhibition > free radical formation, altered signal transduction DNA intercalation in nucleus - blocks DNA/RNA synthesis topo II inhibition forms drug–DNA–enzyme cleavable complex - prevents resealing of DNA breaks and leads to double-stranded breaks - inhibits ability of helicases from dissociating DNA into single strands, blocking DNA replication generation of semiquinone and oxygen free radicals cell cycle-specific > G1/S-phase

Answer 24

enzyme inhibitor > topo II inhibitor > anthracycline > induce apoptosis from DNA damage and topo II inhibition > free radical formation, altered signal transduction DNA intercalation in nucleus - blocks DNA/RNA synthesis topo II inhibition forms drug–DNA–enzyme cleavable complex - prevents resealing of DNA breaks and leads to double-stranded breaks - inhibits ability of helicases from dissociating DNA into single strands, blocking DNA replication generation of semiquinone and oxygen free radicals cell cycle-specific > G1/S-phase

Answer 25

enzyme inhibitor > topo II inhibitor > anthracycline > induce apoptosis from DNA damage and topo II inhibition > free radical formation, altered signal transduction DNA intercalation in nucleus - blocks DNA/RNA synthesis topo II inhibition forms drug–DNA–enzyme cleavable complex - prevents resealing of DNA breaks and leads to double-stranded breaks - inhibits ability of helicases from dissociating DNA into single strands, blocking DNA replication generation of semiquinone and oxygen free radicals cell cycle-specific > G1/S-phase

Answer 26

enzyme inhibitor > anthracenedione

Answer 27

enzyme inhibitor > anthracenedione > epipodophyllotoxin cell cycle-specific > G2-phase

Answer 28

enzyme inhibitor > anthracenedione > epipodophyllotoxin

Answer 29

antimicrotubule agent > vinca alkaloid binds tubulin, inhibits polymerization, disrupts microtubule assembly --> cell cycle arrest (mitotic inhibitor) cell cycle-specific > M-phase (neurons have a lot of tubulin = mechanism of neurotox side effects)

Answer 30

antimicrotubule agent > vinca alkaloid binds tubulin, inhibits polymerization, disrupts microtubule assembly --> cell cycle arrest (mitotic inhibitor) cell cycle-specific > M-phase (neurons have a lot of tubulin = mechanism of neurotox side effects)

Answer 31

antimicrotubule agent > vinca alkaloid binds tubulin, inhibits polymerization, disrupts microtubule assembly --> cell cycle arrest (mitotic inhibitor) vinorelbine may also block glutamic acid utilization > disrupts nucleic acid synthesis proteins cell cycle-specific > M-phase (neurons have a lot of tubulin = mechanism of neurotox side effects)

Answer 32

antimicrotubule agent > taxane - bind polymerized tubulin to enhance polymerization - interferes with microtubule disassembly and blocks mitosis also disrupt endothelial cells and inhibit angiogenesis cell cycle-specific > M-phase

Answer 33

antimicrotubule agent > taxane - bind polymerized tubulin to enhance polymerization - interferes with microtubule disassembly and blocks mitosis also disrupt endothelial cells and inhibit angiogenesis cell cycle-specific > M-phase

Answer 34

antimicrotubule agent > taxane - bind polymerized tubulin to enhance polymerization - interferes with microtubule disassembly and blocks mitosis also disrupt endothelial cells and inhibit angiogenesis cell cycle-specific > M-phase

Answer 35

antimicrotubule agent > taxane - bind polymerized tubulin to enhance polymerization - interferes with microtubule disassembly and blocks mitosis also disrupt endothelial cells and inhibit angiogenesis cell cycle-specific > M-phase

Answer 36

antimicrotubule agent > epothilone binds β tubulin subunits to inhibit microtubule dynamics by promoting tubulin polymerization, causing cellular arrest at G2-M phase cell cycle-specific > M-phase

Answer 37

antimicrotubule agent > halichondrin inhibits microtubule function by binding β tubulin to block G2-M phase; inhibits tubulin polymerization cell cycle-specific > M-phase

Answer 38

asparaginase

Answer 39

- antimetabolites - camptothecins (irinotecan, topotecan) - topo II inhibitors (G1/S)

Answer 40

- etoposide - bleomycin - topo I inhibitors (G2/M)

Answer 41

- vinca alkaloids - taxanes - epothiolones (ixabepilone) - halichondrins (eribulin)

Answer 42

- alkylating agents - anthracyclines - antitumor antibiotics

Answer 43

- cytotoxic effect is exerted on the proportion of cells in the part of cell cycle where agent is active - administration often continuous infusion (schedule dependent)

Answer 44

- cytotoxic effect is exerted on cells in any phase of cell cycle, but also preferentially kills proliferating cells - cell kill is proportional to dosage (dose dependent)

Answer 45

- nitrosoureas (carmustine, lomustine, streptozocin) - temozolomide

Answer 46

- decreased uptake - activation of antiapoptotic or prosurvival pathways - increased drug inactivation (increased expression of glutathione or glutathione-associated proteins, glutathione-S-transferase) - increase in DNA repair enzyme expression or activity note: only partial resistance to bendamustine in the setting of resistance to other alkylating agents

Answer 47

- for stem cell transplant, tablets can be placed in a gelatin capsule for ease of administration - dose-dependent emetic potential, need premeds if ≥ 4 mg/day

Answer 48

take on an empty stomach

Answer 49

- nearly 100% bioavailable - emetic potential, may need premeds - take on empty stomach at bedtime to reduce N/V

Answer 50

- food reduces absorption - take on empty stomach

Answer 51

- CNS concentrations can reach 30-40% of plasma levels - emetic potential, need premeds - take on empty stomach to reduce N/V - do not break capsules

Answer 52

- take on empty stomach - emetic potential, need premeds - interacts with MAOIs, TCAs, SSRIs, and other drugs because its metabolite is a weak MAOI - has disulfiram-like reaction with alcohol

Answer 53

procarbazine - interacts with MAOIs, TCAs, SSRIs, and other drugs because its metabolite is a weak MAOI - avoid these as con meds to prevent serotonin syndrome

Answer 54

Gliadel wafer - administered intracranially into the resection cavity (up to eight wafers) for treatment of glioblastoma topical carmustine ointment or solution - available for mycosis fungoides treatment

Answer 55

bendamustine chlorambucil cyclophosphamide ifosfamide melphalan mechlorethamine

Answer 56

carmustine lomustine streptozocin

Answer 57

myelosupporession - all pts need CBC monitoring nausea/vomiting alopecia reproductive impairment carcinogenic > risk of secondary malignancies

Answer 58

monitor LFTs - requires hepatic adjustment - risk of hepatotox other AEs - hypersensitivity reactions - skin tox - hepatotox

Answer 59

myelosuppression (BBW) monitor seizure activity - risk of acute seizures - ??seizure ppx depending on dose monitor LFTs - not recommended for severe hepatic impairment monitor AUC in high-dose regimens - decr risk of hepatic sinusoidal obstructive syndrome other AEs - skin pigmentation changes - pulmonary fibrosis

Answer 60

BBW - myelosuppression - pulmonary tox monitor pulmonary function (lung CO2 diffusion capacity) pre-chemo and during tx - delayed risk of ILD, dose-related pulmonary tox monitor SCr - requires renal adjustment - renal tox monitor LFTs - not recommended for severe hepatic impairment - hepatotox HIGH risk of N/V if dose > 250 mg/m2, MODERATE risk for lower doses other A/Es - infertility - teratogenic

Answer 61

BBW - myelosuppression not recommended for severe hepatic impairment other AEs - infertility - teratogenic - seizures - pulmonary tox - RARE skin reactions - secondary malignancies

Answer 62

monitor SCr + urinalysis - requires renal adjustment monitor LFTs - not recommended for severe hepatic impairment - hepatotox monitor Na - risk of hypoNa or SIADH other AEs - cardiotox - infertility - hemorrhagic cystitis - alopecia - immunosuppression - pulmonary tox - secondary malignancies

Answer 63

BBW - myelosuppression - hepatic effects - carcinogenic & teratogenic requires renal adjustment monitor LFTs - not recommended for severe hepatic impairment - hepatotox HIGH risk of N/V DDIs - major CYP1A2 substrate

Answer 64

BBW - myelosuppression - hemorrhagic cystitis (monitor urinalysis) - nephrotox monitor neurologic assessments - risk of acute CNS tox monitor SCr - nephrotox (BBW) - requires renal adjustment monitor LFTs - not recommended for severe hepatic impairment - hepatotox HIGH risk of N/V if dose > 2 m/m2/dose other AEs - alopecia - cardiotox - pulmonary tox

Answer 65

BBW - myelosuppression requires renal adjustment monitor LFTs - not recommended for severe hepatic impairment - hepatotox MODERATE/HIGH risk of N/V other AEs - ILD and dose-related pulmonary tox

Answer 66

moderate risk of N/V monitor LFTs - hepatotox

Answer 67

BBW - extravasation - highly toxic: corrosive, carcinogenic, mutagenic, teratogenic HIGH risk of N/V other AEs - tumor lysis syndrome - immunosuppression - infertility - teratogenic - secondary malignancies

Answer 68

BBW - myelosuppression - secondary malignancy - hypersensitivity (injection product) REMS program for Hepazto kit (IV/hepatic delivery system) - potential severe peri-procedural complications (hemorrhage, hepatocellular injury, thromboembolic events) requires renal adjustment HIGH risk of N/V if IV dose ≥ 140 mg/m2, minimal/low risk of N/V if PO other AEs - diarrhea - mucositis - hepatotox - fertility effects - pulmonary tox

Answer 69

requires renal adjustment MODERATE/HIGH risk of N/V other AEs - CNS depression - hypersensitivity - disulfiram-like reaction - infertility - secondary malignancies

Answer 70

BBW - drug toxicities - secondary malignancy monitor SCr - requires renal adjustment - renal tox monitor LFTs - hepatotox HIGH risk of N/V other AEs - diarrhea - CNS effects - glucose intolerance

Answer 71

requires renal adjustment monitor LFTs - hepatotox MODERATE/HIGH risk of N/V if PO dose > 75 mg/m2/day, MODERATE risk if IV other AEs - photosensitivity

Answer 72

BBW - myelosuppression - carcinogenicity requires renal adjustment monitor LFTs - not recommended for severe hepatic impairment - risk of hepatic sinusoidal obstructive syndrome LOW risk of N/V other AEs - mucositis - diarrhea - CNS effects (incl encephalopathy) - skin tox

Answer 73

monitor LFTs - requires hepatic adjustment - not recommended for severe hepatic impairment monitor CPK - rhabdo MODERATE risk of N/V other AEs - capillary leak syndrome - cardiomyopathy DDIs - major CYP3A4 substrate

Answer 74

seizure ppx (phenytoin, BZD, Keppra) - evidence may NOT support routine ppx depending on busulfan dose monitor AUC to optimize exposure and reduce tox, incl sinusoidal obstructive syndrome

Answer 75

Giladel wafer = carmustine implant in brain monitor for: - seizures - impaired wound healing - intracranial hypertension

Answer 76

drug excreted in sweat follow skin protocol during tx and for 48 hrs after: - bathe at least 2x/day - don't wear tight fitting clothing - change bedsheets daily - no occlusive dressings on skin (or must change twice daily)

Answer 77

to prevent hemorrhagic cystitis at doses ≥ 50 mg/kg/dose: - coadminister with mesna

Answer 78

coadminister with mesna to prevent hemorrhagic cystitis - intermittent v continuous v PO encephalopathy - 10-30% neurotox: confusion, lethargy, hallucination, seizure - risk factors: renal dysfunction, hypoalbuminemia - REVERSIBLE within 3 days of stopping ifos - TREAT if severe/symptomatic: methylene blue, thiamine, albumin - SECONDARY PPX for later cycles with methylene blue, thiamine, or albumin [minimal data for primary ppx]

Answer 79

coadministra􀆟on of mesna is necessary with high-dose cyclophosphamide (≥ 50 mg/kg/dose) and ifosfamide to prevent hemorrhagic cystitis mesna conjugates active toxic metabolite (acrolein) to reduce bladder tox various protocols exist for dosing/frequency

Answer 80

INTERMITTENT dosing - 60% of daily ifos dose, give bolus 15 min before, 4 hours after, 8 hours after ifos CONTINUOUS dosing (with ifos continuous infusion): - 20% of total ifos dose as bolus followed by 40% as continuous infusion for 12-24 hrs after ifos PO dosing: - first dose IV as 20% of total ifos dose when starting ifos, then give PO as 40% of total dose at 2 hours and 6 hours after ifos [total dose = 100% ifos] - if pt vomits within 2 hours of dose, repeat dose (IV or PO)

Answer 81

for SEVERE or SYMPTOMATIC ifosfamide-induced encephalopathy (10-30%): - confusion, lethargy, hallucination, seizure methylene blue 50 mg IV or PO q6-8h otherwise, symptoms generally spontaneously reverse within 3 days after d/cing ifos

Answer 82

alkylating agent > platinum analog - inter- or intra-strand DNA crosslinks inhibit DNA synthesis - primary binding site = guanine N7 cell cycle non-specific - cells are most susceptible in G1/S [cisplatin, carboplatin, oxaliplatin]

Answer 83

- DNA damage repair - reduced cellular uptake - inactivation by glutathione, metallothioneins, or thiol-containing proteins if resistant to cisplatin or carboplatin d/t mismatch repair defects --> NOT cross-resistant to oxaliplatin [cisplatin, carboplatin, oxaliplatin]

Answer 84

no oral formulations available

Answer 85

varies per protocol - duration 30 min to 8 hrs - fixed rate 1 mg/min - continuous infusion

Answer 86

varies per protocol - 15 min to 24 hrs

Answer 87

varies per protocol: - 2 to 6 hrs

Answer 88

N/V neurotox

Answer 89

BBW - myelosuppression - N/V - renal tox - peripheral neuropathy monitor CBC, SCr, K, Mg - requires renal adjustment - renal tox (BBW) HIGH risk of N/V pretx hydration and adequate urinary output required +/- amifostine to prevent nephrotox and neutropenia +/- mannitol to prevent nephrotox +/- STS to reduce ototox effects other AEs - hypersensitivity rxns - TLS - neurotox - ocular tox (less common) - secondary malignancies avoid aluminum needles or infusion sets - poss reaction and loss of potency

Answer 90

BBW - myelosuppression - vomiting - hypersensitivity rxns monitor SCr - requires renal adjustment - poss renal tox (less than cis) monitor CBC, lytes, LFTs - hepatotox HIGH risk of N/V if AUC ≥ 4, MODERATE if lower +/- STS to reduce ototox effects other AEs - neurotox (less than cis) avoid aluminum needles or infusion sets - poss reaction and loss of potency

Answer 91

BBW - hypersensitivity rxns monitor CBC, SCr, LFTs - requires renal adjustment - hepatotox MODERATE risk of N/V cold-induced peripheral neuropathy and oropharyngeal dysesthesia - avoid cold beverages - avoid ice chip mucositis ppx +/- STS to reduce ototox effects other AEs - peripheral neuropathy - neurologic sx can be dose-limiting avoid aluminum needles or infusion sets - poss reaction and loss of potency INCOMPATIBLE WITH NS - flush line with D5W before and after infusion - if giving with 5-FU, give oxali FIRST

Answer 92

cross-allergy between agents in this class varies - skin testing - potential rechallenge with alt agent may be done under close supervision desens may be indicated to continue tx after anaphylaxis (thought to be IgE-mediated) - varied protocols, often 4 or 12 steps - allows for TEMPORARY tolerance --> must be performed with each dose desens NOT recommended if: - severe skin rxn (SJS, TEN) - severe serum sickness rxn

Answer 93

use Calvert formula carbo dose = AUC x (GFR + 25) dose capping recommended at max GFR 125 mL/min - consider 24-hr urine creatinine or ethylene diamine tetraacetic acid for patients with AUC > 6 or if using UNCAPPED GFR consider caadjBW for pts with BMI > 25 consider min SCr 0.7 mg/dL for pts with abnormally low SCr (eg. elderly, cachexic)

Answer 94

doses > 100 mg/m2 per tx course NOT recommended may be given intraperitioneally (off-label)

Answer 95

may be used to prevent CISPLATIN nephrotox and neutropenia - alt strategies = dose mods and growth factors MOA = chemoprotectant of healthy cells - scavenges free radicals - minimizes strand breaks - promotes proliferation - stimulates DNA repair - inhibits apoptosis SELECTIVE because healthy cells have the following properties vs tumor cells: - higher capillary alk phos activity - high pH - better vascularity 910 mg/m2 IV over 15 minutes, give 30 minutes before cisplatin - monitor for hypoTN

Answer 96

910 mg/m2 IV over 15 minutes, give 30 minutes before cisplatin - monitor for hypoTN [chemoprotectant for healthy cells]

Answer 97

may be used to prevent CISPLATIN nephrotox proposed MOA - diuretics may decr urinary conc of cisplatin by incr water excretion AND blocking chloride reabsorption dose may vary by cisplatin dosage (eg 12.5 – 25 g)

Answer 98

improved 5-FU efficacy when given with leucovorin - 5-FU inhibits thymidylate synthase (TS) - leucovorin is precursor of reduced folate cofactor that stabilizes binding to TS > prolonged enzyme inhibition vs 5-FU alone leucovorin rescue for HD-MTX (500 mg/m2 or greater) - leucovorin is reduced folate, which allows DNA synthesis in the presence of MT - leucovorin preferentially rescues healthy cells; does NOT eliminate MTX

Answer 99

- diarrhea - mucositis or stomatitis

Answer 100

cladribine clofarabine fludarabine mercaptopurine nelarabine pentostatin thioguanine

Answer 101

azacitidine capecitabine cytarabine decitabine gemcitabine fluorouracil floxuridine trifluridine(/tipiracil)

Answer 102

antiapoptotic mechanisms DNA repair processes

Answer 103

all have minimal to low emetogenicity

Answer 104

5-FU prodrug, 80% bioavailable take in 2 divided doses swallow whole within 30 min of a meal

Answer 105

oral tablet NOT available in the US available in Canada

Answer 106

tablets and suspensions available take on an empty stomach avoid "6-MP" nomenclature, risk of overdose allopurinol DDI - mercaptopurine metabolized to inactive metabolite by xanthine oxidase (XO) - allopurinol inhibits XO > incr mercaptopurine activity/toxicity > NEED DOSE REDUCTION TPMT or NUDT15 deficiency - results in incr mercaptopurine activity/toxicity

Answer 107

take once daily oral suspension can be compounded TPMT or NUDT15 deficiency - results in incr thioguanine activity/toxicity

Answer 108

take twice daily with food swallow whole

Answer 109

results in incr mercaptopurine or thioguanine activity/toxicity HIGH RISK of severe myelosuppression because of overexposure for - ALL TPMT homozygotes - 30%–60% of TPMT heterozygotes

Answer 110

results in incr mercaptopurine or thioguanine activity/toxicity NUDT15 loss-of-function alleles can be common in Asian or Hispanic pts

Answer 111

intermittent or continuous infusion subQ (off-label)

Answer 112

intermittent infusion

Answer 113

intermittent or continuous infusion subQ injection available MAY BE GIVEN INTRATHECALLY - 25-100 mg - must be compounded with PRESERVATIVE-FREE product

Answer 114

intermittent infusion

Answer 115

usually 30 min infusion - infusions > 60 min associated with higher tox (off label) fixed dose rates have been recommended (off label) intravesical bladder irrigation

Answer 116

IV undiluted

Answer 117

IV bolus or intermittent infusion

Answer 118

may aid in recovery after fluorouracil/capecitabine overdose or toxicity

Answer 119

myelosuppression GI tox

Answer 120

monitor SCr - requires renal adjustment - not recommended for severe renal impairment - may cause dehydration, renal failure monitor diarrhea monitor hands/feet - hand-foot syndrome monitor LFTs - hepatotox MINIMAL to LOW risk of N/V other AEs - fetal harm - cardiotox DDIs - weak CYP2C9 inhibitor, monitor warfarin/INR closely

Answer 121

BBW - myelosuppression - IV: neurotox, renal tox - PO: malignancy, teratogenicity monitor CBC - myelosuppression (BBW) - not recommended for severe renal impairment monitor LFTs - not recommended for hepatic impairment - hepatotox monitor for infection - immunosuppression MINIMAL risk of N/V other AEs - hypersensitivity reaction - cardiotox - neurotox, rare progressive multifocal leukoencephalopathy (PML)

Answer 122

monitor CBC - myelosuppression - infection, enterocolitis monitor SCr - requires renal adjustment - not recommended for severe renal impairment monitor LFTs - not recommended for hepatic impairment - hepatotox monitor BP - hypoTN MODERATE risk of N/V other AEs - capillary leak syndrome (CLS) - systemic inflammatory response syndrome (SIRS) - skin tox - bleeding

Answer 123

monitor CBC - myelosuppression (BBW) monitor SCr - requires renal adjustment monitor LFTs - requires hepatic adjustment [for HiDAC] monitor ocular and CNS effects - cerebellar tox - ocular tox - acute pulmonary tox DOSE-DEPENDENT risk of N/V - MODERATE if > 200 mg/m2 (> 1000 mg/m2 per ASCO) - LOW if 100-200 mg/m2 - MINIMAL if < 100 mg/m2 other AEs - mucositis

Answer 124

BBW - myelosuppression - neurotox - autoimmune effects (hemolytic anemia, immune thrombocytic purpura) monitor CBC and for infection - myelosuppression (BBW) - immunosupression monitor SCr - requires renal adjustment - not recommended for severe renal impairment monitor LFTs MINIMAL risk of N/V for IV; MINIMAL to LOW risk of N/V for PO other AEs: - neurological effects

Answer 125

monitor CBC and for signs of infection - myelosuppression LOW risk of N/V other AEs - GI (diarrhea, mucositis) - neurotox - hyperammonemic encephalopathy - hand–foot syndrome - cardiotox - fetal harm DDIs - weak CYP2C9 inhibitor, monitor warfarin/INR closely

Answer 126

monitor CBC - myelosuppression monitor LFTs - requires hepatic adjustment - hepatotox LOW risk of N/V other AEs - hypersensitivity - rare CLS - rare hemolytic uremic syndrome (HUS) - rare posterior reversible encephalopathy syndrome (PRES) - pulmonary tox - radiation recall - fetal tox

Answer 127

monitor CBC - myelosuppression monitor LFTs - not recommended for hepatic impairment - hepatotox monitor skin - rash - photosensitivity MINIMAL to LOW risk of N/V other AEs - secondary malignancies - rare MAH - rare hemophagocytic lymphohistiocytosis (HLH) DDIs - avoid allopurinol: XO inhibition leads to mercaptopurine accumulation > toxicity - avoid azathioprine: metabolized to mercaptopurine, duplicate effects - avoid TPMT inhibitors

Answer 128

monitor CBC - myelosuppression - requires concomitant hydration MINIMAL to LOW risk of N/V other AEs - neurotox

Answer 129

BBW - do NOT give with fludarabine, incr risk of fatal pulmonary tox monitor CBC and for infection - myelosuppression - infection - requires renal adjustment - not recommended for severe renal impairment - rare renal tox - requires concomitant hydration LOW risk of N/V other AEs - rare tox: CNS, skin, liver, pulmonary tox

Answer 130

TPMT/NUDT15 genotyping monitor CBC - myelosuppression monitor LFTs monitor uric acid - hyperuricemia other AEs - photosensitivity - secondary malignancies MINIMAL to LOW risk of N/V

Answer 131

monitor CBC - myelosuppression monitor SCr - requires renal adjustment - not recommended for severe renal impairment monitor LFTs - requires hepatic adjustment MINIMAL to LOW risk of N/V (MODERATE to HIGH per ASCO)

Answer 132

ANC > 1.5 Plt > 100

Answer 133

ANC > 0.75 dose adjustments vary by indication, refer to product label

Answer 134

pentostatin nelarabine

Answer 135

if dihydropyrimidine dehydrogenase (DPD) activity is low or absent, risk of tox increases - hold or d/c tx if unusually severe side effects occur diarrhea - hold tx until resolves to at least gr 1 - use routine antidiarrheal agents - may warrant fluids or lyte repletion

Answer 136

if dihydropyrimidine dehydrogenase (DPD) activity is low or absent, risk of tox increases - hold or d/c tx if unusually severe side effects occur diarrhea - hold tx for gr 3+ until resolves to at least gr 1, then resume with dose reduction - use routine antidiarrheal agents - may warrant fluids or lyte repletion

Answer 137

high-dose cytarabine 1.5 - 3 g/m2

Answer 138

(high-dose cytarabine) ocular tox - presentation: corneal tox, conjunctivitis - ppx with steroid eye drops QID and for 24 hours after last HiDAC dose neurotox - presentation: acute cerebellar tox, personality change, seizure, coma - generally reversible - monitor CNS tox (nystagmus, changes in speech or coordination) before each dose - risk factors: age, renal impairment, high dosage, prior CNS disease

Answer 139

*capillary leak syndrome (CLS) or systemic inflammatory response syndrome (SIRS)* s/sx: - rapid-onset respiratory distress (tachypnea, pulmonary edema) - hypoTN - tachycardia - organ failure reduce risk with prophylactic steroids - hydrocortisone 100 mg/m2 on days 1–3 treatment - hold chemo - give supportive care, steroids, diuretic, albumin CLS or SIRS warrants dose reduction for future doses *INTERMEDIATE risk for infection --> infection ppx per NCCN* antibacterial - FQ while neutropenic antifungal - agent/duration depends on indication - generally during mucositis and while neutropenic anti-Pneumocystis jirovecii (PCP/PJP) - bactrim - continue until CD4 > 200 cells/uL antiviral - acyclovir - while neutropenic, longer depending on risk

Answer 140

(fludarabine, cladribine, clofarabine) INTERMEDIATE risk for infection --> infection ppx per NCCN antibacterial - FQ while neutropenic antifungal - agent/duration depends on indication - generally during mucositis and while neutropenic anti-Pneumocystis jirovecii (PCP/PJP) - bactrim - continue until CD4 > 200 cells/uL antiviral - acyclovir - while neutropenic, longer depending on risk

Answer 141

INTERMEDIATE risk for infection --> infection ppx per NCCN antibacterial - FQ while neutropenic antifungal - agent/duration depends on indication - generally during mucositis and while neutropenic anti-Pneumocystis jirovecii (PCP/PJP) - bactrim - continue until CD4 > 200 cells/uL antiviral - acyclovir - while neutropenic, longer depending on risk

Answer 142

INTERMEDIATE risk for infection --> infection ppx per NCCN antibacterial - FQ while neutropenic antifungal - agent/duration depends on indication - generally during mucositis and while neutropenic anti-Pneumocystis jirovecii (PCP/PJP) - bactrim - continue until CD4 > 200 cells/uL antiviral - acyclovir - while neutropenic, longer depending on risk

Answer 143

methotrexate pemetrexed pralatrexate

Answer 144

- decreased cellular update via reduced folate carrier - decreased polyglutamation - altered target or binding to target - MDR transporter expression

Answer 145

IV, intrathecal, IM, subQ, or PO dosage and infusion duration (slow push, short or 24-hour infusion) vary by indication and regimen - always double check intended dosage, route, and frequency with indication high-dose methotrexate (HD-MTX) is 500–1000 mg/m2 IV or more for adults and 2 g/m2 or more for pediatric patients high-dose regimens should be compounded with PF products to avoid excessive benzyl alcohol intrathecal should be compounded with PF products - 12–15 mg intrathecally for CNS disease via lumbar puncture or Ommaya reservoir (6 mg) ** do NOT give leucovorin intrathecally IM or subQ for noncancer indications (Crohn's, psoriasis)

Answer 146

high-dose methotrexate 500–1000 mg/m2 IV or more for adults and 2 g/m2 or more for pediatric patients

Answer 147

500 mg/m2 IV over 10 minutes on day 1 of 21-day cycle if in combo regimens, give BEFORE platinum or AFTER pembrolizumab

Answer 148

15-30 mg/m2 IV push over 3-5 minutes once a week dose/duration varies by indication

Answer 149

myelosuppression renal impairment GI tox

Answer 150

- myelosuppression - renal impairment - hepatotoxicity - pneumonitis - GI tox - secondary malignancy - TLS - skin tox - opportunistic infections - embryo–fetal toxicity - pregnancy

Answer 151

BWW = many!! monitor CBC - myelosuppression (BBW) + opportunistic infections (BBW) monitor renal function - need renal adjustment - NOT recommended in severe renal impairment - acute renal failure, renal impairment (BBW) monitor LFTs - NOT recommended in severe hepatic impariment - hepatotox (BBW) monitor GI tox (BBW) - diarrhea - stomatitis for HD-MTX, also monitor - MTX levels - urine pH LOW to MODERATE risk of N/V other AEs - CNS effects / neurotox (incl after intrathecal admin) - pneumonitis (BBW) - secondary malignancy (BBW) - TLS (BBW) - embryo-fetal tox (BBW) DDIs - avoid NSAIDs, PPIs, folate-containing vitamins, penicillins, trimethoprim, probenecid, P-glycoprotein/ABCB1 inhibitors

Answer 152

monitor CBC - myelosuppression monitor renal function - need renal adjustment - NOT recommended in severe renal impairment - renal tox - NOT recommended in severe hepatic impairment monitor GI tox - mucositis LOW risk of N/V other AEs - interstitial pneumonitis - hand-foot syndrome - skin tox + radiation recall DDIs - ibuprofen/NSAIDs can reduce clearance --> caution with renal dysfunction; avoid concomitant use

Answer 153

monitor CBC - myelosuppression monitor renal function - need renal adjustment - NOT recommended in severe renal impairment monitor LFTs - hepatotox MINIMAL to LOW risk of N/V other AEs - mucositis - skin tox DDIs - sulfamethoxazole/trimethoprim, NSAIDs, or probenecid --> delayed pralatrexate clearance

Answer 154

ALL - methotrexate, pemetrexed, pralatrexate - all require renal adjustment - NONE recommended in renal impairment

Answer 155

pralatrexate NOT recommended with severe hepatic impairment: - methotrexate - pemetrexed

Answer 156

errors, including deaths, have occurred from inadvertent daily dosing of intended weekly regimens ISMP advises using WEEKLY as default for electronic orders clear patient education concerning specific admin instructions is needed

Answer 157

WBC ≥ 1.5 Plt ≥ 75 TBili =/< 1.2 resolution of mucositis or effusions

Answer 158

1. evaluate renal/hepatic function + fluid status (ascites, effusions) before each cycle - decr elimination in renal/hepatic impairment or with fluid accumulation - risk of delayed clearance and incr tox - consider holding for AKI, severe hepatic dysfunction, or presence of effusions or anasarca 2. evaluate for DDIS and drug-food interactions - avoid NSAIDs, PPIs, folate-containing vitamins, penicillins, trimethoprim, probenecid, P-glycoprotein/ABCB1 inhibitors - avoid acidic beverages (soda, fruit juice) and products (vitamin C) that counteract alkalinization protocols - consider avoiding other con meds that incr risk of renal tox or hepatotox (e.g., azoles)

Answer 159

(at least 500–1000 mg/m2 IV for adults) (at least 2 g/m2 for peds) 1. requires leucovorin (reduced folate) rescue - preferentially rescues healthy cells to allow DNA synthesis in presence of MTX but does not eliminate MTX - DO NOT give intrathecally - usually starts 24 hrs after end of HD-MTX - adjust dose per 1977 Bleyer nomogram (inputs = time after MTX start (x) and plasma [MTX] (y)) 2. requires urine alkalinization - sodium bicarbonate IV or PO - 2024 systematic review/meta-analysis --> no difference in clinical outcomes for IV vs PO although frequency of diarrhea and number of instances of urine pH <7 were higher in those receiving oral - may use acetazolamide IV or PO, particularly during bicarb shortage or if fluid restricted or overloaded 3. evaluate for individual hydration needs to ensure adequate elimination 4. monitor urine pH and MTX levels - goal urine pH 7+ - goal [MTX] < 0.05–0.1 μM at 72 hours 5. manage delayed MTX clearance in setting of renal dysfunction - glucarpidase recommended when plasma [MTX] rises 2 standard deviations above the expected mean per mtxpk.org/simulation model - alternative: if the level is > 30 μM at 36 hours, >10 μM at 42 hours, or > 5 μM at 48 hours

Answer 160

enzyme hydrolyzes MTX into inactive metabolites - approved for patients with delayed MTX clearance due to renal impairment high cost product $$$

Answer 161

50 units/kg IV as single dose; do not redose within 48 hours give within 60 hours of HD-MTX --> delayed initiation may NOT improve clinical outcomes no leucovorin 2 hours before or after glucarpidase may be administered intrathecally (off-label) immunoassay result may overestimate [MTX] after glucarpidase, because it cannot distinguish metabolites --> chromatographic evaluation needed for accurate reading if level drawn < 48 hours of glucarpidase dose high cost product $$$

Answer 162

ANC ≥ 1.5 Plt ≥ 100 CrCl ≥ 45 mL/min adjust dose for: - myelosuppression - mucositis - diarrhea - renal dysfunction

Answer 163

1. decr myelosuppression with: - folic acid 400–1,000 mcg daily continuously - vitamin B12 1,000 mcg IM before then q3cycles start 1 week before chemo and continue through 21 days after last dose 2. decr skin tox with dexamethasone 4 mg PO BID starting day before chemo x3 days each cycle 3. hand-foot syndrome can be managed with steroids

Answer 164

ANC ≥ 1 Plt ≥ 50 (≥ 100 for first dose) mucositis less than gr 2 adjust dose for: - mucositis - hepatotox

Answer 165

1. decr myelosuppression with: - folic acid 1,000-1,250 mcg daily continuously - vitamin B12 1,000 mcg IM before then q8-10wks start 10 days before chemo and continue through 30 days after last dose

Answer 166

anthracyclines - daunorubicin - doxorubicin - idarubicin - epirubicin anthracenediones - mitoxantrone epipodophyllotoxins - etoposide - teniposide

Answer 167

daunorubicin doxorubicin liposomal doxorubicin - also in Vyxeos (liposomal doxorubicin + cytarabine) idarubicin epirubicin mitoxantrone (anthracenedione - structurally similar to anthracyclines)

Answer 168

(Vyxeos = liposomal formulation of daunorubicin in combination with cytarabine) NOT interchangeable with conventional daunorubicin or cytarabine products product is a fixed 1:5 daunorubicin to cytarabine molar ratoo to provide synergistic impact on cellular killing dosed in daunorubicin component and administered IV MAO: side effects (including prolonged cytopenia) and monitoring are related to individual components; see individual drug info

Answer 169

DNA intercalation in nucleus - blocks DNA/RNA synthesis topo II inhibition forms drug–DNA–enzyme cleavable complex - prevents resealing of DNA breaks and leads to double-stranded breaks - inhibits ability of helicases from dissociating DNA into single strands, blocking DNA replication generation of semiquinone and oxygen free radicals - one-electron reduction leads to reactive compounds, causing widespread damage to DNA and cell membrane - resulting anthracycline–iron complex binds and cleaves DNA to generate free radicals, which damage DNA and cell membranes. - results in incr damage to cells (e.g., cardiac tissue) with fewer enzymes that convert radicals to less reactive compounds other MOAs - altered cell membrane and plasma membrane-associated events, such as fluidity and ion transport - activate signal transduction pathways

Answer 170

efflux out of cell via MDR pumps (eg. P-gp) reduced topoisomerase II activity BCL-2 overexpression TP53 mutation DNA repair mechanisms defenses against free radicals

Answer 171

IV push or infusion lower doses at more frequent intervals or prolonged infusions can reduce toxicity (nausea, cardiotoxicity) continuous infusion may increase mucositis

Answer 172

IV push or infusion lower doses at more frequent intervals or prolonged infusions can reduce toxicity (nausea, cardiotoxicity) continuous infusion may increase mucositis

Answer 173

IV infusion over 60 minutes - first dose may be given at 1 mg/min to reduce infusion reaction lower doses at more frequent intervals or prolonged infusions can reduce toxicity (nausea, cardiotoxicity) continuous infusion may increase mucositis

Answer 174

IV slow push or intermittent infusion over 15 minutes lower doses at more frequent intervals or prolonged infusions can reduce toxicity (nausea, cardiotoxicity) continuous infusion may increase mucositis

Answer 175

IV slow push or intermittent infusion over 15 minutes lower doses at more frequent intervals or prolonged infusions can reduce toxicity (nausea, cardiotoxicity) continuous infusion may increase mucositis

Answer 176

IV infusion over 5-15 minutes lower doses at more frequent intervals or prolonged infusions can reduce toxicity (nausea, cardiotoxicity) continuous infusion may increase mucositis

Answer 177

BBW for ALL - myelosuppression - cardiotox / cardiomyopathy - extravasation (all except liposomal doxorubicin) secondary malignancies radiation sensitizers

Answer 178

- CBC - LFTs - cardiac function only for daunorubicin + idarubicin: - renal function

Answer 179

monitor CBC - myelosuppression (BBW) monitor renal function - requires renal adjustment - renal tox (BBW) monitor LFTs - requires hepatic adjustment - hepatotox (BBW) monitor cardiac function - cardiotox (BBW) monitor infusion - extravasation (vesicant) (BBW) MODERATE risk of N/V other AEs - red urine - alopecia DDIs - P-gp substrate

Answer 180

monitor CBC - myelosuppression (BBW) monitor LFTs - requires hepatic adjustment - NOT recommended in severe hepatic impairment - hepatotox (BBW) monitor cardiac function - cardiotox (BBW) monitor infusion - extravasation (vesicant) (BBW) MODERATE/HIGH risk of N/V other AEs - red urine - radiation recall - fertility impairment - secondary malignancies (BBW) DDIs - major CYP3A4 and CYP2D6 substrate - P-gp substrate

Answer 181

monitor CBC - myelosuppression (BBW) monitor LFTs - requires hepatic adjustment - NOT recommended in severe hepatic impairment - hepatotox (BBW) monitor cardiac function - cardiotox (BBW) monitor infusion - infusion reactions (irriitant) (BBW) LOW risk of N/V (unique to liposomal formulation, otherwise moderate/high) other AEs - red urine - radiation recall - fertility impairment - secondary malignancies - palmar–plantar erythrodysesthesia (unique to liposomal formulation) DDIs - major CYP3A4 and CYP2D6 substrate

Answer 182

monitor CBC - myelosuppression (BBW) monitor renal function - requires renal adjustment - renal tox (BBW) monitor LFTs - requires hepatic adjustment - NOT recommended in severe hepatic impairment - hepatotox (BBW) monitor cardiac function - cardiotox (BBW) monitor infusion - extravasation (vesicant) (BBW) MODERATE risk of N/V DDIs - P-gp substrate

Answer 183

monitor CBC - myelosuppression (BBW) monitor LFTs - requires hepatic adjustment - NOT recommended in severe hepatic impairment monitor cardiac function - cardiotox (BBW) monitor infusion - extravasation + tissue necrosis (vesicant) (BBW) MODERATE to HIGH risk of N/V other AEs: - alopecia - thrombotic events - radiation recall - secondary malignancies (BBW)

Answer 184

monitor CBC - myelosuppression (less than anthracyclines) (BBW) - requires hepatic adjustment monitor cardiac function - cardiotox (BBW) monitor infusion - extravasation (BBW) - hypersensitivity reaction LOW risk of N/V other AEs - secondary malignancies (BBW) - blue-green urine, tears, saliva, eyes - alopecia - mucositis

Answer 185

temporary urine discoloration (red) signs of extravasation symptoms of cardiotoxicity myelosuppression

Answer 186

temporary urine discoloration (red) signs of extravasation symptoms of cardiotoxicity myelosuppression

Answer 187

temporary urine discoloration (red) symptoms of cardiotoxicity myelosuppression **(risk of infusion reaction as an irritant, not an extravasation risk since not a vesicant)

Answer 188

signs of extravasation symptoms of cardiotoxicity myelosuppression

Answer 189

signs of extravasation symptoms of cardiotoxicity myelosuppression

Answer 190

temporary urine, tears, saliva, and eye discoloration (blue/green) signs of extravasation symptoms of cardiotoxicity myelosuppression

Answer 191

primary concern = cardiotoxicity pre-tx - LVEF should be > 50% acute s/sx (transient, usually < 3 days of chemo) - may be asymptomatic - acute arrhythmia, conduction abnormalities, pericarditis, myocarditis - monitor EKG chronic s/sx (months to years after chemo) - dilated cardiomyopathy, heart failure - caused by oxygen free radicals - dose-dependent tox monitoring: - LVEF via ECHO/MUGA - prior or cumulative anthracycline dose limit risk with lifetime max dose: - doxorubicin up to 500 mg/m2 - daunorubicin up to 550 mg/m2 - epirubicin up to 900 mg/m2 - idarubicin up to 150 mg/m2 (not well established). lower weekly dosages or continuous infusion may reduce risk in adults

Answer 192

preexisting heart disease HTN / dyslipidemia / diabetes smoking obesity concurrent cardiotoxic chemotherapy administration before or concurrent with irradiation to chest > 65 years old or young children

Answer 193

up to 500 mg/m2

Answer 194

up to 550 mg/m2

Answer 195

up to 900 mg/m2

Answer 196

(not well established) up to 150 mg/m2

Answer 197

may be used for antracycline extravasation or to prevent anthracycline cardiotox chemoprotectant - exact mechanism is not well known - displaces iron from anthracycline (iron chelator) peds - dexrazoxane may be added based on total cumulative dose of anthracycline being given all patients - if high-dose anthracycline, consider cardioprotectant, liposomal doxorubicin, or continuous-infusion doxorubicin - ESMO recommends dexrazoxane if > 300 mg/m2 anthracycline, esp if preexisting cardiomyopathy is present balance risk of cardiotox v risk of secondary neoplasms

Answer 198

FDA indicated to prevent doxoubicin-induced cardiomyopathy given as 10:1 dexrazoxane:doxorubicin IV - 50% dose reduction if CrCl < 40 mL/min (5:1) primarily studied in advanced or metastatic disease and high-dose anthracycline use - ASCO guideline does NOT make recommendation for low-dose anthracyclines

Answer 199

if s/sx - ECHO, cardiac MRI, or MUGA - serum cardiac biomarkers (eg. troponins, BNP) if concerning results found - refer to cardiologist - start cardioprotective agents if evidence of cardiac sx, even if asymptomatic (eg. ACE-I, beta blocker) consider adjusting chemo regimen (risk of ongoing cardiotox vs. maintaining efficacy of cancer tx)

Answer 200

no consensus! - may consider ECHO/MUGA as routine surveillance, esp if high risk ESMO recs for asymptomatic pts: - screen cardiac biomarkers (troponin, BNP) - image at 6-12 mos, then 2 yrs post-tx, then periodically thereafter NCCN recs: - image within 1 yr of completing tx if high dose and 1+ risk factors present

Answer 201

etoposide teniposide

Answer 202

etoposide enzyme inhibitor > topo II inhibitor (epipodophyllotoxin)

Answer 203

topo II inhibition forms drug–DNA–enzyme cleavable complex - prevents resealing of DNA breaks and leads to double-stranded breaks - inhibits ability of helicases from dissociating DNA into single strands, blocking DNA replication cell cycle-specific > G1/S-phase

Answer 204

MDR + P-gp overexpression --> reduced accumulation in cells altered target (topo II) expression mutations in target (topo II) altered DNA repair processes

Answer 205

IV over 30-60 minutes - contains polysorbate-80 --> administer via non-PVC tubing - concentration must be < 0.4 mg/mL; may give undiluted (in dextrose or NS) - consider use of in-line filter - certain plastics, acrylic, or ABS may crack/leak when used with undiluted etoposide - irritant PO once daily - if 200 mg+, may give in two divided doses - 50% bioavailable - may use IV product to compound oral formulation

Answer 206

ANC > 0.5 Plt > 50

Answer 207

IV over 30-60 minutes prepare with non-DEHP sets

Answer 208

monitor CBC - myelosuppression (BBW) monitor renal function + LFTs - adjust dose for renal or hepatic dysfunction monitor BP - hypoTN monitor infusion - hypersensitivity LOW risk of N/V if IV; MODERATE to HIGH risk of N/V if PO other AEs - dose-related mucositis - alopecia - secondary malignancies DDIs - major CYP3A4 substrate - P-gp substrate

Answer 209

monitor CBC - myelosuppression (BBW) - NOT recommended in severe hepatic dysfunction monitor BP - hypoTN monitor infusion - hypersensitivity (BBW) other AEs - mucositis DDIs - major CYP3A4 substrate - P-gp substrate

Answer 210

risk of hypersensitivity higher with: - IV product - undiluted product - rapid administration - formulations with polysorbate-80 or benzyl alcohol

Answer 211

monitor for hypoTN and hypersensitivity risk of secondary malignancies if PO, adherence

Answer 212

monitor for hypoTN and hypersensitivity risk of secondary malignancies

Answer 213

camptothecins - irinotecan - topotecan

Answer 214

topo I inhibition via formation of stable cleavable complexes --> interferes with DNA replication and formation of ssDNA breaks --> cell cycle arrest

Answer 215

(topo I inhibitors = irinotecan, topotecan) topo I mutation decreased drug accumulation in cells (not d/t MDR/P-gp, but variable expression of carboxylesterases) DNA repair mechanisms

Answer 216

liposomal irinotecan is NOT interchangable with conventional irinotecan conventional IV over 90 minutes liposomal is given q2w irritant

Answer 217

IV or PO IV over 30 minutes, irritant PO +/- food - swallow whole - IV solution may be given orally with acidic juice (1 mg/mL in up to 30 mL juice)

Answer 218

(irinotecan and topotecan = topo I inhibitors) myelosuppression GI effects: nausea, diarrhea, mucositis

Answer 219

monitor CBC - myelosuppression (BBW) monitor renal function and LFTs - requires renal adjustment - renal tox - requires hepatic adjustment - hepatotox monitor GI sx - diarrhea (BBW) - cholinergic syndrome, incl acute diarrhea MODERATE risk of N/V other AEs: - hypersensitivity - pulmonary tox - alopecia UGT1A1*28 - increased active metabolite (SN-38) if polymorphism present (homozygous or heterozygous)

Answer 220

monitor CBC - myelosuppression (BBW) - requires renal adjustment monitor LFTs - NOT recommended in severe hepatic impairment - hepatotox monitor GI sx - stomatitis, mucositis - mild diarrhea monitor adherence (if PO) LOW risk of N/V in adults; MODERATE risk of N/V if PO in peds other AEs - rash - neutropenic enterocolitis - hypersensitivity - pulmonary tox

Answer 221

irinotecan is a prodrug that is activated via carboxylesterases to potent active metabolite SN-38 increased SN-38 levels if UGT1A1*28 polymorphism is present --> greater tox

Answer 222

ANC ≥ 1.5 Plt ≥ 100 resolved diarrhea (if tx-related)

Answer 223

diarrhea --> can be dose-limiting and FATAL (BBW) acute - usually within 1 hr of completion (or within 24 hrs) - likely r/t cholinergic effects - ppx w/ atropine 0.25 - 1 mg IV or subQ delayed (> 24 hrs after) - more common w/ q3w than weekly regimens - treat with antimotility agents (loperamide 4 mg x1 then 2-4 mg q2-4 hrs until diarrhea resolved for at least 12 hrs) --> ma 48 hours of use - if refractory: octreotide or tincture of opium - if fever, severe neutropenia or ileus: may need abx monitor hydration / lytes

Answer 224

anticholinergic agent that counteracts cholinergic effects of irinotecan infusion (cramping, diaphoresis, salivation, rhinitis, lacrimation, flushing) use as prophylaxis for acute diarrhea following irinotecan infusion 0.25 - 1 mg IV or subQ

Answer 225

baseline - ANC ≥ 1.5 - Plt ≥ 100 later cycles - ANC ≥ 1 - Plt ≥ 100 - Hgb ≥ 9

Answer 226

docetaxel paclitaxel nab-paclitaxel cabazitaxel

Answer 227

antimicrotubule agent > taxane - bind polymerized tubulin to enhance polymerization - interferes with microtubule disassembly and blocks mitosis also disrupt endothelial cells and inhibit angiogenesis cell cycle-specific > M-phase

Answer 228

altered tubulin or tubulin-binding sites P-gp overexpression - cabazitaxel is a poor P-gp substrate

Answer 229

hypersensitivity reactions - usually within first 10 minutes of first infusion - 1-3% incidence with premedication myelosuppression

Answer 230

monitor CBC - neutropenia (BBW) monitor infusion - hypersensitivity (BBW) - usually within first 10 minutes of first infusion - 1-3% incidence with premedication LOW risk of N/V other AEs - diarrhea - rare pulmonary tox DDIs - major 3A4 substrate - adjust dose for STRONG CYP3A4 inhibitor

Answer 231

monitor CBC - neutropenia (BBW) monitor infusion - hypersensitivity (BBW) - usually within first 10 minutes of first infusion - 1-3% incidence with premedication LOW risk of N/V other AEs - fluid retention (BBW) - may be cumulative, give dex premed, may resolve when tx stopped - hepatotox (BBW) - alopecia - skin tox - neurotox - secondary malignancies - weakness/fatigue DDIs - major 3A4 substrate - avoid OR adjust dose for STRONG CYP3A4 inhibitor

Answer 232

monitor CBC - myelosuppression (BBW) monitor infusion - hypersensitivity (BBW) - usually within first 10 minutes of first infusion - 1-3% incidence with premedication LOW risk of N/V other AEs - hypoTN - cardiac tox, arrhythmias - alopecia - neurotox (mainly neuropathy)

Answer 233

monitor CBC - neutropenia (BBW) less hypersensitivity that conventional paclitaxel - lack of Cremophor excipient less neuropathy than conventional paclitaxel

Answer 234

20 mg/m2 IV q3w IV over 1 hr via filter avoid polyurethane or PVC infusion sets premeds (for hypersensitivity) - antihistamine, H2RA, + steroid at least 30 min before may contain polysorbate-80 and alcohol

Answer 235

ANC > 1.5 adjust dose for myelosuppression or diarrhea

Answer 236

IV over 1 hr through non-DEHP tubing product may contain alcohol premeds (to reduce hypersensitivity + fluid retention) - if treating prostate cancer with docetaxel + prednisone --> dexamethasone 8 mg PO 12 hours, 3 hours, 1 hour before chemo - otherwise.. dexamethasone 8 mg BID starting day before infusion x3 days

Answer 237

ANC > 1.5 adjust dose for myelsuppression, skin tox, diarrhea, and stomatitis (may vary per indication)

Answer 238

IV over 1, 3, or 24 hrs - 3 hrs most commonly use non-PVC infusion set with filter premeds (for hypersensitivity) - diphenhydramine, H2RA, + dexamethasone product contains Cremophor (polyethoxylated castor oil) - do NOT use if history of severe hypersensitivity to drug or excipient product may contain alcohol

Answer 239

ANC ≥ 1.5 (≥ 1 for Kaposi sarcoma)

Answer 240

30 minute infusion low risk of hypersensitivity d/t lack of Cremophor excipient premedication may be needed if prior mild/mod hypersensitivity reaction occurred

Answer 241

ANC ≥ 1.5 (less myelosuppression than paclitaxel, but similar neuropathy)

Answer 242

vincristine vinblastine vinorelbine

Answer 243

antimicrotubule agent > vinca alkaloid binds tubulin, inhibits polymerization, disrupts microtubule assembly --> cell cycle arrest (mitotic inhibitor) vinorelbine may also block glutamic acid utilization > disrupts nucleic acid synthesis proteins cell cycle-specific > M-phase (neurons have a lot of tubulin = mechanism of neurotox side effects)

Answer 244

alteration in tubulin subtypes or tubulin expression P-gp / MDR > prevents intracellular accumulation

Answer 245

IV ONLY DO NOT administer INTRATHECALLY --> pain, paralysis, ascending motor/sensory neuropathy, encephalopathy, and DEATH NEVER dispense any vinca alkaloid in a syringe, use minibags

Answer 246

no renal adjustment hepatic adjustment required for all (vincristine, vinblastine, vinorelbine) ALL are major CYP3A4 substrates - prodrugs are metabolized to active drugs

Answer 247

- myelosuppression - constipation - peripheral neuropathy - syndrome of inappropriate antidiuretic hormone secretion (SIADH) - jaw pain - vesicants - neurotox (neuropathy, autonomic dysfunction incl orthostatic hypoTN, constipation, paralytic ileus, urinary retention) MINIMAL risk of N/V

Answer 248

neutropenia is a DLT for vinblastine and vinorelbine higher incidence of neuropathy with vincristine

Answer 249

monitor CBC - myelosuppression monitor LFTs - hepatic adjustment required (major CYP3A4 substrate, prodrugs are metabolized to active drugs) monitor infusion - extravasation (BBW) - IV use only (BBW) MINIMAL risk of N/V other AEs: - alopecia - neurotox (neuropathy, autonomic dysfunction incl orthostatic hypoTN, constipation, paralytic ileus, urinary retention) DDIs: - major CYP3A4 substrate, prodrugs are metabolized to active drugs

Answer 250

monitor LFTs - hepatic adjustment required (major CYP3A4 substrate, prodrugs are metabolized to active drugs) - hepatotox monitor peripheral neuropathy - dose-related, cumulative monitor constipation monitor infusion - extravasation (BBW) - IV use only (BBW) MINIMAL risk of N/V other AEs: - alopecia - myelosuppression DDIs: - major CYP3A4 substrate, prodrugs are metabolized to active drugs

Answer 251

monitor CBC - myelosuppression (BBW) monitor LFTs - hepatic adjustment required (major CYP3A4 substrate, prodrugs are metabolized to active drugs) - hepatotox monitor constipation and neuropathy MINIMAL risk of N/V DDIs: - major CYP3A4 substrate, prodrugs are metabolized to active drugs

Answer 252

usually 1.4 mg/m2 cap at 2 mg to minimize neuropathy aggressive bowel regimen may be necessary to prevent ileus all vinca alkaloids require dose adjustment for: - hematologic tox - neuropathy - hepatic dysfunction

Answer 253

dose varies by indication all vinca alkaloids require dose adjustment for: - hematologic tox - neuropathy - hepatic dysfunction

Answer 254

dose varies by indication all vinca alkaloids require dose adjustment for: - hematologic tox - neuropathy - hepatic dysfunction

Answer 255

ixabepilone

Answer 256

not affected by overexpression of P-gp or tubulin mutations

Answer 257

not affected much by P-gp

Answer 258

40 mg/m2 IV over 3 hours q3w - cap dose at 2.2 m2 (88 mg) IV only - MUST be reconstituted with diluent provided by manufacturer - use non-DEHP infusion set with filter premeds (1 hour before) - H1 blocker (diphenhydramine) - H2 blocker (famotidine, ranitidine) - [only if history of reaction] add dexamethasone contains - ethanol (may experience cognitive dysfunction or discoordination - Cremophor (do NOT give if prior reaction to drug or excipient) no oral formulation

Answer 259

1.4 mg/m2 IV on days 1,8 q3w IV only - infuse over 2-5 min - may be administered undiluted - INCOMPATIBLE with dextrose no oral formulation

Answer 260

no renal adjustment not recommended in severe hepatic impairment do NOT give in combination with capecitabine if - AST/ALT > 2.5 x ULN or - TBili > ULN

Answer 261

no renal adjustment not recommended in severe hepatic impairment

Answer 262

monitor CBC - myelosuppression (mostly neutropenia) monitor LFTs - hepatotox (BBW) other AEs - neurotoxicity (sensory and motor) - hypersensitivity reaction DDIs - major CYP3A4 substrate (recommended to avoid concomitant strong CYP3A4 inhibitors or inducers)

Answer 263

monitor CBC - myelosuppression monitor LFTs - NOT recommended for severe hepatic impairment monitor SCr - renal adjustment required monitor QT prolongation LOW risk of N/V other AEixas - neurotox - alopecia

Answer 264

contraindicated with capecitabine if - AST/ALT > 2.5 x ULN or - TBili > ULN - ANC < 1.5 - Plt < 100 - history of severe hypersensitivity reaction to drug or excipient (Cremophor) modify dose for - myelosuppression - hepatotox - concurrent strong CYP3A4 inhibitors/inducers

Answer 265

- ANC > 1 - Plt > 75 - non-heme tox < grade 3 modify dose for - renal or hepatic impairment

Answer 266

epigenetic modifier > histone deacetylase (HDAC) inhibitor > leads to accumulation of acetylated histones > apoptosis HDAC enzymes usually catalyze removal of acetyl groups from lysine - pro-oncogenic effect = allows apoptosis genes to be transcriptionally quiescent

Answer 267

epigenetic modifier > histone deacetylase (HDAC) inhibitor > leads to accumulation of acetylated histones > apoptosis HDAC enzymes usually catalyze removal of acetyl groups from lysine - pro-oncogenic effect = allows apoptosis genes to be transcriptionally quiescent

Answer 268

epigenetic modifier > histone deacetylase (HDAC) inhibitor > leads to accumulation of acetylated histones > apoptosis HDAC enzymes usually catalyze removal of acetyl groups from lysine - pro-oncogenic effect = allows apoptosis genes to be transcriptionally quiescent

Answer 269

epigenetic modifier > histone deacetylase (HDAC) inhibitor > leads to accumulation of acetylated histones > apoptosis HDAC enzymes usually catalyze removal of acetyl groups from lysine - pro-oncogenic effect = allows apoptosis genes to be transcriptionally quiescent

Answer 270

belinostat dose adjustment is needed for reduced UGT1A1 activity (homozygous for UGT1A1*28 allele)

Answer 271

cardiac events (ECG changes, QT prolongation) - monitor for concomitant QT-prolonging agents gastrointestinal notably, minimal myelosuppression

Answer 272

monitor CBC - minimal myelosuppression monitor LFTs - hepatotox monitor cardiac events - EKG/QT changes - limit QT prolonging drugs (DDI) monitor GI sx - diarrhea LOW risk of N/V genetic testing - dose adjustment needed for reduced UGT1A1 activity (homozygous for UGT1A1*28 allele) - belinostat is UGT1A1 substrate

Answer 273

monitor CBC - minimal myelosuppression - infection (HBV, EBV, pneumonia) - consider antiviral ppx if history of HBV infection monitor EKG, K, Mg - arrythmia - EKG/QT changes - limit QT prolonging drugs (DDI) MODERATE risk of N/V DDIs - monitor INR with concurrent warfarin

Answer 274

monitor CBC / thrombosis - minimal myelosuppression - DVT, pulmonary embolism monitor glucose - hyperglycemia monitor EKG - EKG/QT changes - limit QT prolonging drugs (DDI) monitor GI sx - diarrhea MINIMAL/LOW risk of N/V DDIs - monitor INR with concurrent warfarin

Answer 275

1000 mg/m2 IV on days 1-5 q3w - 30 min infusion - needs in-line filter

Answer 276

ANC >/= 1 Plt >/= 50

Answer 277

14 mg/m2 IV on days 1,8,15 q4w - 4 hour infusion

Answer 278

ANC >/= 1.5 Plt >/= 75

Answer 279

400 mg PO daily with food swallow whole may be compounded into a suspension

Answer 280

azacitidine and decitabine also antimetabolites (pyrimidine analogs)

Answer 281

1. ANTIMETABOLITE, PYRIMIDINE ANALOG - azacitidine incoporated into DNA/RNA - decitabine incorporated into DNA only 2. EPIGENETIC MODIFIER - inhibit DNA methylation - methylation silences gene expression and hypomethylation allows gene reactivation (altered regulation of tumor suppressor/driver genes) cell cycle-specific (S phase)

Answer 282

(azacitidine, decitabine) deletion of uridine-cytidine kinase, which ACTIVATES the drug increase in cytidine deaminase, which INACTIVATES the drug

Answer 283

monitor CBC - myelosuppression monitor LFTs, renal function - hepatotox - renal tox monitor injection site reactions (subQ) LOW/MODERATE risk of N/V for IV; MODERATE/HIGH risk of N/V for PO

Answer 284

monitor CBC - myelosupression monitor LFTs, renal function LOW/MINIMAL risk of N/V

Answer 285

monitor CBC - myelosupression monitor LFTs, renal function MINIMAL/LOW risk of N/V - GI tox is mild/transient

Answer 286

IV or subQ or PO - PO and IV/subQ are NOT interchangable use not recommended if albumin < 30 g/L or advanced malignant hepatic tumor present IV - 10 - 40 min infusion - 1 hr stability of reconstituted vials - polysorbate 80 may be in some formulations, monitor for reaction - treat for at least 4 cycles to assess response PO - daily on days 1-14 q4w - give predose antiemetic before each dose for at least first 2 cycles

Answer 287

IV - 1 - 3 hour infusion depending on indication and regimen - if admin will be > 15 min later, dilute with cold NS or D5W to final concentration - treat for at least 4 cycles to assess response subQ has been used off-label with lower responses

Answer 288

PO combination product - take tablet daily on empty stomach monitor CBC before each treatment - may need to delay or reduce dose for myelosuppression

Answer 289

bortezomib carfilzomib ixazomib

Answer 290

proteasomes regulate intracellular protein degradation via the ubiquitin–proteasome pathway - ubiquitin marks proteins for degradation by the 26S proteasome (19S + 20S subunits) bortezomib and ixazomib reversibly, and carfilzomib irreversibly, bind the 26S proteasome - blocks degradation of IκB → IκB accumulates and inhibits NF-κB - NF-κB remains sequestered in the cytoplasm, preventing transcription of pro-survival and pro-proliferation genes

Answer 291

proteasomes regulate intracellular protein degradation via the ubiquitin–proteasome pathway - ubiquitin marks proteins for degradation by the 26S proteasome (19S + 20S subunits) REVERSIBLY binds the 26S proteasome - blocks degradation of IκB → IκB accumulates and inhibits NF-κB - NF-κB remains sequestered in the cytoplasm, preventing transcription of pro-survival and pro-proliferation genes

Answer 292

proteasomes regulate intracellular protein degradation via the ubiquitin–proteasome pathway - ubiquitin marks proteins for degradation by the 26S proteasome (19S + 20S subunits) IRREVERSIBLY binds the 26S proteasome - blocks degradation of IκB → IκB accumulates and inhibits NF-κB - NF-κB remains sequestered in the cytoplasm, preventing transcription of pro-survival and pro-proliferation genes

Answer 293

proteasomes regulate intracellular protein degradation via the ubiquitin–proteasome pathway - ubiquitin marks proteins for degradation by the 26S proteasome (19S + 20S subunits) REVERSIBLY binds the 26S proteasome - blocks degradation of IκB → IκB accumulates and inhibits NF-κB - NF-κB remains sequestered in the cytoplasm, preventing transcription of pro-survival and pro-proliferation genes

Answer 294

poorly defined; gene expression and mutations may contribute if resistant to bortezomib, may use carfilzomib or ixazomib after

Answer 295

neuropathy - bortezomib >> carfilzomib/ixazomib - cumulative, dose-limiting - management: (a) IV to subQ, (b) decrease dose, (c) twice weekly to once weekly, (d) treat with gabapentin, pregabalin, TCA, or SNRI herpes zoster reactivation - antiviral ppx recommended rare: - posterior reversible encephalopathy syndrome (PRES) - thrombotic microangiopathy - hepatotox

Answer 296

monitor CBC - myelosuppression monitor LFTs - hepatotoxicity monitor blood pressure - hypotension monitor for neuropathy - high risk (dose-limiting; cumulative) monitor for herpes reactivation - antiviral ppx recommended LOW risk of N/V other AEs - tumor lysis syndrome - rare cardiopulmonary effects DDIs CYP3A4/2C19 substrate (avoid strong inducers)

Answer 297

monitor CBC - myelosuppression monitor LFTs - not recommended in severe hepatic impairment monitor SCr - rare renal toxicity monitor blood pressure - HTN - cardiotox (higher in older adults, screen BEFORE tx start) monitor for infusion reaction - especially early in treatment monitor for neuropathy - lower incidence than bortezomib monitor for herpes reactivation - antiviral ppx recommended LOW risk of N/V other AEs - cardiopulmonary toxicity - tumor lysis syndrome

Answer 298

monitor CBC - myelosuppression monitor LFTs, SCr - requires dose adjustment for both monitor for neuropathy - lower risk than bortezomib monitor for herpes reactivation - antiviral ppx recommended LOW risk of N/V other AEs - rash - peripheral edema DDIs CYP3A4 & P-gp substrate (avoid strong inducers)

Answer 299

IV or subQ - subQ preferred (lower incidence of neuropathy than IV) - IV and subQ are reconstituted differently (use caution) doses must be separated by at least 72 hours do NOT give intrathecally, death has occurred

Answer 300

modify dose for myelosuppression, neuropathy, or hepatic impairment

Answer 301

IV - 10 - 30 min infusion - dose cap at BSA 2.2 m2 (per PI) - no dose adjustment if weight change is 20% or less (per PI) premeds before each dose in cycle 1 and prn to decrease infusion reaction risk - dexamethasone 4 mg IV (or PO if monotherapy) hydration recommended before each cycle 1 dose, then prn after and for subsequent cycles

Answer 302

modify dose for - myelosuppression - cardiac or pulm tox - neuropathy - hepatic or renal dysfunction

Answer 303

4 mg PO weekly (d1,8,15 q4w) - take 1 hr before/2 hrs after meal - swallow whole - skip missed dose if next dose within 72 hours

Answer 304

subQ bortezomib

Answer 305

modify dose for - myelosuppression - neuropathywh - rash - hepatic or renal dysfunction

Answer 306

bleomycin dactinomycin mitomycin trabectedin

Answer 307

antitumor antibiotic - binds iron → forms bleomycin–iron complex - generates free radicals → causes single- & double-strand DNA breaks - DNA damage occurs via oxidation of DNA–bleomycin–iron complex - inactivated by aminohydrolase (low in skin/lung → toxicity) cell cycle non-specific

Answer 308

antitumor antibiotic - inhibits RNA and protein synthesis - prevents transcription of single-stranded DNA cell cycle non-specific

Answer 309

antitumor antibiotic - Alkylates DNA → causes cross-links - inhibits DNA replication - most effective in hypoxic tumor environments cell cycle non-specific

Answer 310

antitumor antibiotic - alkylates DNA - binds guanine to form adducts - triggers apoptosis via DNA damage response pathways cell cycle non-specific

Answer 311

monitor CBC - minimal myelosuppression monitor LFTs - hepatotoxicity (infrequent) monitor pulmonary function tests - pulmonary fibrosis, pneumonitis (BBW) LOW risk of N/V other AEs - dermatologic effects (e.g., hyperpigmentation, rash) - idiosyncratic reactions: fever, chills, hypotension, wheezing inactivated by bleomycin hydrolase (low in skin/lung → toxicity)

Answer 312

monitor CBC - myelosuppression - secondary malignancies monitor LFTs - hepatotoxicity (e.g., veno-occlusive disease) MODERATE risk of N/V other AEs - dermatologic effects - radiation recall

Answer 313

monitor CBC - myelosuppression (BBW) monitor SCr - avoid if CrCl < 30 mL/min or dialysis monitor for HUS - hemolytic uremic syndrome (BBW) LOW risk of N/V other AEs - pulmonary effects - cardiac tox DDIs P-gp substrate

Answer 314

monitor CBC - myelosuppression monitor LFTs - hepatotoxicity (dose-limiting) monitor creatine phosphokinase - rhabdomyolysis risk → check before each dose monitor cardiac function - cardiotox - pulmonary embolism MODERATE risk of N/V other AEs - capillary leak syndrome - embryo–fetal toxicity DDIs - major CYP3A4 & P-gp substrate

Answer 315

IV - 5 - 30 units/m2 IV over 10 min, frequency varies per indication test dose may be given IM, IV, or subQ as 2 units or less - wait at least 1 hr before giving rest of dose - false negatives may occur also IM, subQ, or intrapleural - may be given intrapleurally for malignant pleural effusion as 60 units in 50–100 mL of NS

Answer 316

monitor diffusing capacity of lung for CO2 - if less than 35% of baseline --> discontinue monitor diffusing capacity of lung for CO2 corrected for Hgb - if decrease more than 25% from baseline --> discontinue

Answer 317

IV or isolated limb infusion protocol (solid tumors) dose and schedule vary per indication - may be in mg or mcg dose adjustment recommended for concomitant radiation

Answer 318

IV, intravesicular, or transcatheter arterial chemoembolization (intra-arterial) dose varies per indication - usually IV push via central catheter (vesicant)

Answer 319

dose and schedule vary per indication - 3 hr or 24 hr infusion - infuse via central line using in-line filter premeds - dexamethasone 20 mg IV before every infusion

Answer 320

reduce dose for - myelosuppression - hepatotox - CPK elevation - decr LVEFw - cardiomyopathy

Answer 321

arsenic trioxide (As2O3) all-trans retinoic acid (ATRA; tretinoin)

Answer 322

differentiating agent - damages PML-RARA fusion protein → induces apoptosis in APL cells - causes DNA fragmentation and morphologic changes - also impacts apoptotic pathways and generates reactive oxygen species (ROS)

Answer 323

(ATRA; all-trans retinoic acid) differentiating agent - binds PML-RARA fusion protein - activates transcription → induces differentiation of APL cells - reduces proliferation by promoting leukemic cell maturation MOA for toxicity - rapid differentiation causes integrin expression on leukemia cells - leads to clogging of small vessels → risk of differentiation syndrome (e.g., pleural/pericardial effusions, dyspnea)

Answer 324

monitor QT interval (baseline & weekly ECG) - QT prolongation (BBW) - rare: torsades, ventricular tachycardia, sudden death monitor electrolytes (K⁺, Mg²⁺, Ca²⁺) - maintain: K⁺ > 4, Mg²⁺ > 1.8, Ca²⁺ WNL monitor LFTs - hepatotox monitor for differentiation syndrome (BBW) - fever, weight gain, effusions, renal changes monitor for encephalopathy (BBW) MODERATE risk of N/V - premeds recommended other AEs - leukocytosis - secondary malignancies - embryo–fetal toxicity - carcinogenic DDIs - monitor for additive QT prolongation risk

Answer 325

(ATRA, all-trans retinoic acid) monitor LFTs - hepatotox - monitor coags - DIC, especially early in therapy monitor for differentiation syndrome (BBW) - fever, weight gain, dyspnea, edema - may require steroid ppx or temporary discontinuation monitor for leukocytosis (BBW) - can require treatment interruption monitor for pseudotumor cerebri - particularly in pediatric patients LOW risk of N/V other AEs - teratogenic (BBW) → 2 forms of contraception & pregnancy testing required - ↑ cholesterol/triglycerides DDIs - CYP3A4 substrate

Answer 326

0.15 mg/kg IV over 1–2 hrs (up to 4 hrs if vasomotor symptoms) - Frequency/duration vary by induction vs. consolidation - IV only (no oral formulation) - does not require central line, but is a vascular irritant consider steroid ppx for differentiation syndrome (depends on pt-specific factors) - prednisone 0.5 mg/kg/day or dexamethasone 10 mg q12h - from day 1 to end of induction - taper is recommended adjust dose for CrCl < 30 mL/min or dialysis

Answer 327

45 mg/m²/day PO in two divided doses - duration varies by induction, consolidation, and maintenance protocols PO only - take with food - do not crush capsules - if needed, can be given sublingually or via NG tube (compounded liquid) hazardous drug: use PPE when handling start ATRA immediately if APL is suspected; don’t delay for genetic confirmation - discontinue if t(15;17)/PML-RARA is not confirmed

Answer 328

dexamethasone 10 mg IV q12h for at least 3 days and until s/sx resolve

Answer 329

if positive --> confirms APL diagnosis start ATRA immediately if APL is suspected; don’t delay for genetic confirmation - discontinue if t(15;17)/PML-RARA is not confirmed

Answer 330

peg-asparaginase (Oncaspar) calaspargase pegol-mknl (Asparlas) erwinia chrysanthemi–derived asparaginase (Erwinaze) asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze)

Answer 331

- catalyze conversion of L-asparagine (non-essential amino acid) in cancer cells → aspartic acid + ammonia - depletes extracellular L-asparagine → halts protein synthesis in lymphoid cancer cells - leads to apoptosis cell cycle specific (G1 phase)

Answer 332

asparaginase enzyme - catalyze conversion of L-asparagine (non-essential amino acid) in cancer cells → aspartic acid + ammonia - depletes extracellular L-asparagine → halts protein synthesis in lymphoid cancer cells - leads to apoptosis cell cycle specific (G1 phase)

Answer 333

asparaginase enzyme - catalyze conversion of L-asparagine (non-essential amino acid) in cancer cells → aspartic acid + ammonia - depletes extracellular L-asparagine → halts protein synthesis in lymphoid cancer cells - leads to apoptosis cell cycle specific (G1 phase)

Answer 334

asparaginase enzyme - catalyze conversion of L-asparagine (non-essential amino acid) in cancer cells → aspartic acid + ammonia - depletes extracellular L-asparagine → halts protein synthesis in lymphoid cancer cells - leads to apoptosis cell cycle specific (G1 phase)

Answer 335

asparaginase enzyme - catalyze conversion of L-asparagine (non-essential amino acid) in cancer cells → aspartic acid + ammonia - depletes extracellular L-asparagine → halts protein synthesis in lymphoid cancer cells - leads to apoptosis cell cycle specific (G1 phase)

Answer 336

arise from either immunologic sensitization (e.g., hypersensitivity reactions) or protein depletion (e.g., thrombotic events) hypersensitivity reactions (mild to anaphylaxis; IV > IM risk) pancreatitis hepatotoxicity coagulopathy → bleeding or thrombosis hyperglycemia, hypertriglyceridemia, hyperammonemia fatigue, neurotoxicity higher toxicity in adults

Answer 337

occurs in up to 30% of patients, usually within 30–60 minutes - consider splitting infusion (e.g., 10% over first hour, 90% in second hour) to detect early signs symptoms - urticaria, rash, fever, chills, flushing, somnolence, anaphylaxis monitor asparaginase activity levels - detects silent (subclinical) hypersensitivity (antibodies with no symptoms) - ~10% incidence; may require switch to Erwinia product risk - IV > IM premeds - APAP, antihistamines, steroids - may reduce risk but can mask clinical symptoms if hypersensitivity to peg-asparaginase, switch to Erwinia-based product - hypersensitivity can occur ANY TIME after switching - observe 1 hour post-dose do NOT interchange products

Answer 338

monitor CBC - myelosuppression monitor LFTs - hepatotox - consider L-carnitine/vitamin B for bilirubin > 3 mg/dL or LFTs > 3 × ULN monitor amylase/lipase - pancreatitis (discontinue if > 3 × ULN + symptoms or pseudocyst) monitor coags (fibrinogen, PT/INR, aPTT) - risk of coagulopathy, bleeding - give cryoprecipitate if fibrinogen < 80 monitor ATIII - thrombosis risk; replete if ≤ 50% monitor glucose, TGs - hyperglycemia, hypertriglyceridemia monitor ammonia prn - hyperammonemia, somnolence observe 1 hr post-dose - hypersensitivity (fever, rash, urticaria, anaphylaxis) other AEs - fatigue - neurotox

Answer 339

monitor CBC - myelosuppression monitor LFTs - hepatotox - consider L-carnitine/vitamin B for bilirubin > 3 mg/dL or LFTs > 3 × ULN monitor amylase/lipase - pancreatitis (discontinue if > 3 × ULN + symptoms or pseudocyst) monitor coags (fibrinogen, PT/INR, aPTT) - risk of coagulopathy, bleeding - give cryoprecipitate if fibrinogen < 80 monitor ATIII - thrombosis risk; replete if ≤ 50% monitor glucose, TGs - hyperglycemia, hypertriglyceridemia observe 1 hr post-dose - hypersensitivity (including delayed or masked by premedication) other AEs - neurotox - hyperammonemia - fatigue

Answer 340

monitor CBC - myelosuppression monitor LFTs - hepatotox - consider L-carnitine/vitamin B for bilirubin > 3 mg/dL or LFTs > 3 × ULN monitor amylase/lipase - pancreatitis (discontinue if > 3 × ULN + symptoms or pseudocyst) monitor coags (fibrinogen, PT/INR, aPTT) - risk of coagulopathy, bleeding - give cryoprecipitate if fibrinogen < 80 monitor ATIII - thrombosis risk; replete if ≤ 50% monitor glucose, TGs - hyperglycemia, hypertriglyceridemia monitor ammonia prn - hyperammonemia observe 1 hr post-dose - hypersensitivity (still possible despite switching) other AEs - N/V (higher risk at >20,000 IU/m² IV) - neurotox - fatigue

Answer 341

monitor CBC - myelosuppression monitor LFTs - hepatotox - consider L-carnitine/vitamin B for bilirubin > 3 mg/dL or LFTs > 3 × ULN monitor amylase/lipase - pancreatitis (discontinue if > 3 × ULN + symptoms or pseudocyst) monitor coags (fibrinogen, PT/INR, aPTT) - risk of coagulopathy, bleeding - give cryoprecipitate if fibrinogen < 80 monitor ATIII - thrombosis risk; replete if ≤ 50% monitor glucose, TGs - hyperglycemia, hypertriglyceridemia observe 1 hr post-dose - hypersensitivity reactions other AEs - hyperammonemia - neurotox - fatigue

Answer 342

do NOT interchange products dosing - ≤ 21 yrs: 2,500 IU/m² - > 21 yrs: 2,000 IU/m² - do not give more often than every 14 days - cap dose at 1 vial (3,750 IU) IV over 1–2 hrs or deep IM (separate injections if volume > 2 mL) - subQ used off-label hypersensitivity - consider premeds: APAP, diphenhydramine, steroid (but may mask hypersensitivity/inefficacy, prefer therapeutic drug monitoring) - may give 10% of dose over first hour, 90% over second hour

Answer 343

do NOT interchange products 2,500 IU/m² IV q3w - do not give more often than every 21 days hypersensitivity - consider premeds: APAP, diphenhydramine, steroid (but may mask hypersensitivity/inefficacy, prefer therapeutic drug monitoring) - may give 10% of dose over first hour, 90% over second hour

Answer 344

do NOT interchange products 25,000 IU/m² - 3x/week for 6 doses - IV over 1–2 hrs (with filter) or deep IM (separate injections if volume > 2 mL) - subQ used off label hypersensitivity - consider premeds: APAP, diphenhydramine, steroid (but may mask hypersensitivity/inefficacy, prefer therapeutic drug monitoring) - may give 10% of dose over first hour, 90% over second hour

Answer 345

do NOT interchange products 25 mg/m² IM q48h OR 25 mg/m² IM Mon/Wed AM and 50 mg/m² IM Fri PM IM only; no IV formulation - separate injections if volume > 2 mL hypersensitivity - consider premeds: APAP, diphenhydramine, steroid (but may mask hypersensitivity/inefficacy, prefer therapeutic drug monitoring) - may give 10% of dose over first hour, 90% over second hour

Answer 346

used to detect silent inactivation or subclinical hypersensitivity measure nadir serum asparaginase activity (NSAA) - suggested target: ≥ 0.1 IU/mL - NSAA is especially important in patients with prior hypersensitivity or using Erwinia products

Answer 347

DEXAMETHASONE - asparaginase depletion in hepatic proteins may reduce dex metabolism - patients with asparaginase allergy may have lower asparaginase, resulting in higher dex clearance METHOTREXATE - for about 10–14 days after dose of asparaginase, inhibits efficacy by depleting protein synthesis --> cells are unable to enter S phase where MTX is efficacious - asparaginase can inhibit MTX polyglutamation leading to lower retention in cellsen

Answer 348

altered influx or efflux - folate carriers - ABC proteins (incl MDR/P-gp, BCRP) altered metabolism altered target expression altered DNA repair altered cell division antiapoptotic mechanisms - mutated tumor suppressors (p53) - incr antiapoptotic proteins (BCL-2, FLIP)

Answer 349

assess frailty/functional status - use a systematic geriatric or frailty assessment why it matters - geriatric assessment can predict treatment-related adverse effects and survival - frailty may predict treatment-related morbidity/mortality - screening tools may have limited data on predicting short-term toxicities

Answer 350

assess barriers to care - transportation for infusions & follow-up (esp. homeless/rural) - avoid central IV access if IV drug use is suspected - caregiver availability is important supportive care - palliative care can start at diagnosis and run concurrently with treatment - involve social work and psycho-oncology

Answer 351

educate at appropriate level - use verbal + written formats - confirm understanding with teach-back method monitor oral adherence - consider cognitive ability - use adherence tools: calendars, pillboxes, alarms, apps resource - Oncology Nursing Society’s (ONS) Oral Adherence Toolkit

Answer 352

evaluate financial burden - screen for financial assistance programs - complete precertification for medications when possible resource - Oncology Nursing Society’s (ONS) Toolkit includes links to financial support programsihch

Answer 353

"azoospermia", per ASCO: alkylating agents: cyclophosphamide, chlorambucil procarbazine cisplatin

Answer 354

"permanent amenorrhea", per ASCO: alkylating agents in general high-risk regimens: - Bu/Cy (busulfan + cyclophosphamide) - Cy/total body irradiation for HCT - CMF (cyclophosphamide, methotrexate, fluorouracil)

Answer 355

refer interested patients (male and female) for fertility counseling assess risks and benefits of delaying chemo for fertility preservation follow ASCO guidelines for specific fertility preservation strategies

Answer 356

obtain pregnancy test in all women of childbearing potential - do not rely on absence of menstruation as a marker of infertility counsel both sexes on need for effective contraception - requirements vary by agent

Answer 357

alkylating agents (e.g., mechlorethamine > cyclophosphamide) anthracyclines (topoisomerase II inhibitors) epipodophyllotoxins (etoposide, teniposide – topo II inhibitors)

Answer 358

alkylating agents risk of lung, breast, and skin cancers typically appears 10–20 years after initial exposure

Answer 359

SOLID TUMOR latency ~10–20 years - lung, breast, skin - - - MDS/AML latency ~5–7 years post-treatment risk factors - high cumulative doses - concomitant epipodophyllotoxin use genetic predispositions - Neurofibromatosis type 1 - Fanconi anemia (DNA repair defect) - glutathione transferase theta 1 polymorphism common cytogenetics - deletion of chromosome 5 or 7 prognosis - worse than de novo disease

Answer 360

monitor for leukemia: - associated with 11q23 translocation (MLL gene) - also: 11:20 translocation (NUP98 gene) - anthracenedione (e.g., mitoxantrone) carries higher risk than other anthracyclines common chromosomal abnormalities - 7q, 20q, 1q, 13q - not typically 11q23 with anthracenediones latency & prognosis - unclear impact of dose/schedule - prognosis may mirror de novo AML

Answer 361

etoposide, teniposide (topoisomerase II inhibitors) monitor for AML - latency ~2–3 years post-exposure (shorter than alkylators) - most commonly associated with AML chromosomal abnormalities - 11q23 translocation (MLL gene) - also changes in chromosomes 3, 8, 15, 16, 17, 21, or 22 risk factors - frequent administration - high cumulative dose (data conflicting) - concomitant medications - genetic polymorphisms prognosis - similar to de novo AML

Answer 362

back pain nausea, flushing hypoTN, tachycardia dyspnea feeling of impending doom

Answer 363

Immediate: - IgE-mediated - mast cell activation delayed (non-immediate): - exanthema - serum sickness (Type III) - sSCARs (e.g., SJS, TEN, DRESS) → DO NOT rechallenge

Answer 364

IgE-mediated degranulation direct mast cell/basophil activation nonimmune histamine release / cytokine storm mixed reactions possible

Answer 365

taxanes - mast cell/histamine-mediated - may have IgE-mediated component d/t Cremophor or taxane moeity platinum agents - often IgE-mediated after ≥ 6 doses others - etoposide - procarbazine - asparaginase - doxorubicin - 5-FU

Answer 366

reaction timing - during 1st or 2nd infusion presentation - flushing, dyspnea, urticaria - atypical pain (chest, back) - GI symptoms - hypoTN prevention - premedicate with antihistamines and corticosteroids reactions may be related to Cremophor or drug itself

Answer 367

reaction timing - occurs after ≥6 doses presentation - flushing, pruritus - dyspnea, hypotension, anaphylaxis - back/pelvic pain, fever, chills prevention - premeds not necessary skin testing - may help predict reaction - if positive: consider desensitization - if negative: still at risk, monitor closely

Answer 368

mild reactions - slow infusion rate - administer antihistamines (e.g., diphenhydramine) moderate/severe reactions - epinephrine, corticosteroids, bronchodilators, oxygen - stop infusion; consider desensitization for future doses

Answer 369

rapid drug desensitization = RDD goal - induce temporary tolerance to allow continued treatment protocol - 12-step serial dilution protocol - high success rate (e.g., Brigham and Women’s model) requirements - crash cart, ICU access, trained team - may pause/resume, extend or modify phases if symptoms occur

Answer 370

best evidence for platinum and taxane compounds positive test → proceed with rapid drug desensitization (RDD) if treatment required negative test → may follow with drug provocation test (DPT)

Answer 371

drug provocation test = DPT controlled re-challenge in low-risk patients - used to avoid unnecessary desensitization must include: - 1:1 nurse-to-patient ratio - allergist present - emergency meds & ICU access available

Answer 372

acute dermatologic reaction at the site of prior radiation - triggered by subsequent chemotherapy occurs >7 days after radiation, usually days to weeks - can occur years later - if < 7 days --> this is called radiation enhancement

Answer 373

dactinomycin doxorubicin taxanes gemcitabine capecitabine ( may occur with any agent )

Answer 374

localized rash, dry skin, pruritus, swelling maculopapular eruptions, vesicles, or papules usually mild, but ulcers or necrosis can occur if severe

Answer 375

withdraw causative agent educate patient: - avoid skin irritants - wear protective clothing - use sunscreen provide supportive care - topical steroids - NSAIDs - antihistamines surgery only for severe, nonhealing ulcers

Answer 376

no known prevention longer interval between radiation and chemotherapy may reduce risk may not recur with rechallenge

Answer 377

unintentional leakage of drug into surrounding tissue during IV administration causes direct cell death and progressive tissue damage can occur via peripheral or central lines (e.g., catheter migration, occlusion) ~7% of chemo-related AEs

Answer 378

pain or discomfort redness and swelling slowed infusion or resistance no blood return from IV line

Answer 379

exfoliants → peeling and inflammation inflammitants → inflammation or erythema without pain irritants → inflammation and pain without tissue necrosis vesicants → can cause tissue necrosis or blistering

Answer 380

extravasant - causes peeling and inflammation - cisplatin - docetaxel - mitoxantrone - oxaliplatin - paclitaxel

Answer 381

extravasant - causes inflammation or erythema without pain - 5-fluorouracil - bortezomib - methotrexate

Answer 382

extravasant - causes inflammation and pain without tissue necrosis - bendamustine - carboplatin - etoposide - bleomycin - arsenic trioxide

Answer 383

extravasant - causes tissue necrosis or blistering - cisplatin - oxaliplatin - mechlorethamine - anthracyclines - antitumor abx (bleomycin, dactino, mitomycin, mitoxantrone) - vinca alkaloids - docetaxel - paclitaxel

Answer 384

patient and provider education use of central lines for high-risk agents ensure appropriate vein selection and needle placement follow institutional chemotherapy administration guidelines

Answer 385

stop the infusion immediately aspirate any residual drug (do not flush the line) elevate the affected limb for 48 hours apply a compress (cool or warm based on agent) for 20 (15–30) minutes 4x/day for 24–48 hours - cool compress → vasoconstriction (most agents) warm compress → vasodilation (for vinca alkaloids only)

Answer 386

exfoliant - causes peeling and inflammation irritant (< 0.4 mg/mL) - causes inflammation and pain without tissue necrosis vesicant - causes tissue necrosis or blistering antidote = subQ sodium thiosulfate or topical DMSO cold compress

Answer 387

exfoliant - causes peeling and inflammation irritant - causes inflammation and pain without tissue necrosis vesicant - causes tissue necrosis or blistering antidote = hyaluronidase cold compress

Answer 388

exfoliant - causes peeling and inflammation vesicant - causes tissue necrosis or blistering antidote = DMSO cold compress

Answer 389

exfoliant - causes peeling and inflammation irritant - causes inflammation and pain without tissue necrosis vesicant - causes tissue necrosis or blistering antidote = sodium thiosulfate cold compress - may reduce local injury but may worsen neuropathy - but warm compress may incr drug removal but incr cellular uptake and injury

Answer 390

exfoliant - causes peeling and inflammation irritant - causes inflammation and pain without tissue necrosis vesicant - causes tissue necrosis or blistering antidote = hyaluronidase cold compress

Answer 391

inflammitant - causes inflammation or erythema without pain

Answer 392

inflammitant - causes inflammation or erythema without pain

Answer 393

inflammitant - causes inflammation or erythema without pain

Answer 394