Angela's Chemotherapy Flashcards

Question

Which drug cannot be given as IP chemotherapy? - cyclophosphamide - 5-FU - doxorubicin - paclitaxel

Answer 1

cyclophosphamide because it requires activation by liver P450 microsomal oxidase system Not 5FU - it can be used in IP and discussed as such in Chi Others that require liver activation CANNOT: Ifosfamide (also requires activation by P450 system) Excess toxicity given IP (per Chi): - mitoxantrone - doxorubicin

Answer 2

cardiomyocyte necrosis

Answer 3

Cyclophosphamide

Answer 4

Cimetidine (weak inhibitor of CP450, may worsen myelotoxicity by increasing concentrations of cyclophos/ifos)

Answer 5

Sedation and possible accumulation of toxic metabolites Barbiturates are CY450 INDUCERS —> increased metabolism of cyclophos/ifos, which increases the rate of these drugs to their toxic metabolites Cyclophosphamide may block metabolism of barbiturates, increasing their sedative effects

Answer 6

1. Metabolism? Hepatic 2. Main toxicity? Myelosuppression 3. Excretion? Urinary 4. When do you dose-reduce? Hemorrhagic cystitis (also renal impairment) 5. Prodrug? YES - 4-hydroxycyclophosphamide. Peripheral tiss convers to toxic phosphoramide mustard and acrolein) FYI: During hepatic metabolism of both cyclophosphamide and ifosfamide, acrolein is generated, filtered by the kidneys, and concentrated in the bladder--> Hemorrhagic cystitis. Acrolein is a reactive, unsaturated aldehyde that causes cell death through upregulation of reactive oxygen species, and that activates inducible nitric oxide synthase, leading to the production of nitric oxide.

Answer 7

Alkylating agent that prevents cell division by cross-linking DNA strands (Intra>interstrand) and decreasing DNA synthesis (DNA adducts). **Cell cycle phase nonspecific** but causes arrest and death in G2. Also possesses potent immunosuppressive activity.

Answer 8

Cyclophosphamide Ifosfamide

Answer 9

Prodrug - requires hepatic metabolism for an active metabolite

Answer 10

1. Metabolism? Hepatic 2. Excretion? Urine 3. Prodrug? YES - acrolein, chloracetaldehyde 4. Major toxicity? Myelosuppression

Answer 11

1. Hepatic 2. Urinary 3. Yes - acrolein, chloracetaldehyde 4. Myelosuppresion

Answer 12

Alkylating agent. Causes cross-linking of strands of DNA by binding with nucleic acids and other intracellular structures, resulting in cell death. Inhibits protein synthesis and DNA synthesis. **Cell cycle non-specific**

Answer 13

- Hypoalbuminemia or elderly - Chloracetaldehyde, methylene blue

Answer 14

Acrolein, Mesna (sodium-2-mercaptoethane sulfonate/ 2-**M**ercapto**E**thane **S**ulfonate **Na**) Mesna is oxidized to dimesna in blood, which in turn is reduced in the kidney back to mesna, supplying a free thiol group which binds to and inactivates acrolein

Answer 15

66% if >150 mg/kg

Answer 16

INCREASE - CY450 inhibition

Answer 17

DECREASE - CY450 inducer It causes faster accumulation of toxic byproducts. may block metabolism of barbs leading to greater neurotoxicity/sedating effects of phenobarbital

Answer 18

Nothing, it is activated in the liver Remember vesicants DAMN TV Doxorubicin (also Epirubicin/ idarubicin/ daunorubicin) ActinomycinD Mitomycin C Nitrogen mustard Trabectedin vincas (Vinblastine, vincristine, vinorelbine)

Answer 19

Yes Most common here are: microtubule agents (taxanes), anthracyclanes, topoisomerase inhibitors, and alkylating agents

Answer 20

More slowly. Resulting in more chloracetaldehyde and neurotoxicity

Answer 21

Prolonged myleosuppression with nadir at 30 days and 40 day recovery *alkylating agent.

Answer 22

Alkylating agent Not cell cycle specific

Answer 23

1. Metabolism? Enzymatic inactivation by bleomycin-hydrolase, found in most normal tissues **except lungs and skin** 2. Excretion? Urinary 3. Prodrug? No 4. Main acute toxicity? Mucocutaneous - rash, striae, pruritis, hyperpigmentation. Pulmonary fibrosis. —> bc bleomycin-hydrolase not in lungs and skin, this is where toxicity is!

Answer 24

Pulmonary fibrosis when > 400 units | Per SGO handbook, max cumulative dose should be capped at 270u

Answer 25

Gold standard: Carbon monoxide diffusing capacity (DLCO) - needs to be done **with each cycle of bleo** Cheapest is physical exam (crackles)

Answer 26

G2 phase Chi: G1, G2, S

Answer 27

- Iron chelators enter cells, bind free iron, and remove it from the body - Doxorubicin and bleomycin (chelation causes free-radical formation that results in cardiac or pulmonary toxicity)

Answer 28

Binds to DNA leading to **single** and double strand breaks --> inhibits synthesis of DNA, RNA, and protein synthesis. Binds to guanosine-cytosine-rich portions of DNA via association of the "S" tripeptide and by partial intercalation of the bithiazole rings Also is an iron chelator which results in ROS | Angela's says single-strand breaks, UpToDate says single and double

Answer 29

Skin, lungs

Answer 30

Cumulative cardiac toxicity PharmD: Risk for cardiomyopathy increases at cumulative dose 550 over 18. Test answer on pharmacy exams is usually 550 but no one ever pushes that high since the recommendation to start dexrazoxane is at 300mg/m2 which is probably why you’re seeing that range! SGO states some centers limit the lifetime cumulative dose to no more than 450 mg/m2.

Answer 31

1. Hepatic (think: Hepatic metabolism for Heart toxicity) 2. Cardiac - CHF 3. 450mg/m2 (there is conflicting info between 400-550) From PharmD: Risk for cardiomyopathy increases at cumulative dose 550 over age 18. Incidence is 1 to 20% from 300mg/m2 to 500mg/‘m2 if given every 3 weeks. Test answer on pharmacy exams is usually 550 but no one ever pushes that high since the recommendation to start dexrazoxane is at 300mg/m2 which is probably why you’re seeing that range!

Answer 32

Dexrazoxane but if not available, then DMSO DMSO and cold packs Dimethylsulfoxide (DMSO) Dmso for Doxorubicin (D for D)

Answer 33

dactinomycin (Actinomycin D), doxorubicin, gemcitabine

Answer 34

increases hepatic clearance of doxorubicin and decreases serum concentration by inducing P450 system

Answer 35

No, but it is most active in S-phase

Answer 36

1) Inhibits DNA and RNA synthesis by intercalation between DNA base pairs 2) Inhibition of topoisomerase II 3) Steric obstruction - intercalates at points of local uncoiling of the double helix 4) Iron chelator - produces free radicals that cleave the DNA and cell membranes.

Answer 37

Neutropenia (nadir day 10-12)

Answer 38

Taxol first then cis - avoids increased myelosuppression

Answer 39

24h - increased myelosuppression 3h - increased neurotoxicity

Answer 40

1) Promotes microtubule assembly by enhancing action of tubulin dimers, then stabilizes and inhibits disassembly at G2-M transition --> inhibits cell replication 2) Can distort mitotic spindles, resulting in the breakage of chromosomes 3) May also suppress cell proliferation and modulate immune response **M-phase specific**

Answer 41

1) Hepatic - highly protein-bound 2) Hypersensitivity (urticaria, angioedema) - usually due to solvent castor oil [Cremaphor]), alopecia, peripheral neuropathy (cumulative dose-dependent), **bradycardia**

Answer 42

1) Inhibits DNA synthesis by forming DNA cross-links (inter-strand and intra-strand by binding two adjacent guanines) --> strand breakage 2) Denatures the double helix 3) Covalently binds to DNA bases and disrupts DNA function; may also bind to proteins

Answer 43

1) Nonenzymatic - inactivated by glutathione and thiosulfate 2) Urine 3) Neurotoxicity, nausea/vomiting, nephrotoxicity, ototoxicity, dose-dependent ovarian failure

Answer 44

1) **Decreased uptake**: Downregulation of CTR1 (Copper transporter 1) 2) **Inactivation by glutathione**: Elevated levels of enzymes involved in GSH synthesis (gamma-glutamylcystein synthestase) and glutathione S transferase (binds to platinum inactivating it) 3) **Nuclear excision repair (NER) pathway** : expression of ERCC1 leads to increased repair of platinum-DNA adducts (THIS most common) 4) **DNA MMR**: loss of function of MMR contributes to developing DNA damage tolerance 5) loss of pro apoptotic factors or over expression of anti-apoptotic factors Increased damage tolerance, decreased drug accumulation, increased glutathione levels, enhanced DNA repair, May be related to ERCC1 (excision repair cross complementation group 1)

Answer 45

Hypomagnesemia Hyponatremia

Answer 46

Cisplatin (30%)

Answer 47

Stocking-glove neuropathy, focal encephalopathy, cortical blindness

Answer 48

The process by which chloride is displaced by H2O, activating cis and carboplatinum

Answer 49

Electrical-like pain or shock with neck flexion. Is seen with RT to the spine and some chemo (platinum). (Lhermitte’s *syndrome* is eye issues).

Answer 50

Nephrotoxicity

Answer 51

Interfere with loop of henle and distal convoluted tubule

Answer 52

Thrombocytopenia

Answer 53

Better in predicting myelosuppression than BSA

Answer 54

Usually after 6+ cycles

Answer 55

1) Alkylating agent which covalently binds to DNA 2) Interferes with the function of DNA by producing interstrand DNA cross-links **not cell-cycle specific**

Answer 56

1) Minimally hepatic - aquation 2) Urine 3) Myelosuppression esp thrombocytopenia, nephrotoxicity, electrolyte disturbance (decreased Ca, Mg, K, Na), nausea/vomiting

Answer 57

Causes single strand DNA breaks followed by religation Topoisomerase I: cleaves ONE DNA strand and pass either one or two strands through the break before resealing it Topoisomerase II: cleaves TWO DNA strands in concert and pass another double strand through the break followed by religation of the double strand break

Answer 58

Causes double strand DNA breaks followed by religation Topoisomerase I: cleaves ONE DNA strand and pass either one or two strands through the break before resealing it, Topoisomerase II: cleaves TWO DNA strands in concert and pass another double strand through the break followed by religation of the double strand break

Answer 59

Inhibition of topoisomerase-1, stabilizing the cleavage complex so that re-ligation of DNA breaks cannot occur --> accumulation of ssDNA breaks (topoteCan Cleavage Complex) **S phase specific** I thought it specific to G2 and S - Jenny Megan: Chi says S

Answer 60

Myelosuppression

Answer 61

1) Metabolism? Renal —> 35% protein bound DECIM TDP 2) Excretion? Renal and hepatic - dose reduce only for renal impairment 3) Best pH to function? Acidic (low pH) 4) Water soluble? Yes

Answer 62

Topo-2 inhibitor causing dsDNA strand breaks Forms a complex with topoisomerase II and DNA. Etoposide Poisons topoisomerase II by stabilizing an otherwise transient form of topoisomerase II by covalent linking to DNA. normal topoisomerase II activity is blocked. This causes protein linked DNA strand breaks May also generate O2 free radicals **G2-phase specific**

Answer 63

1) Hepatic - highly protein bound —> DECIM TDP 2) Urine (requires renal dosing) —> A BICC THE MMP 3) NO - it’s an IRRITANT - If extravasation - but treat with HEAT and hyaluronidase Irritants: TICE Taxol, ifosfamide, cisplatin, etoposide

Answer 64

Binds to the guanine portion of DNA intercalating between guanine and cytosine base pairs --> inhibiting DNA and RNA synthesis and protein synthesis G1 max killing, but non-cell cycle specific

Answer 65

Vesicant - potential to cause tissue necrosis with a more severe and/or lasting injury Irritants - inflammation but rarely result in direct toxicity to the tissue Apply COLD to promote vasoconstriction EXCEPT vinca alkaloids, taxanes and etoposide - apply HEAT Vesicants: DAMN TV Doxorubicin (Anthracyclines - dexrazoxane > DMSO), ActinomycinD, no treatment Mitomycin C, DMSO Nitrogen mustard, Trabectedin, vincas (Hyaluronidase) Irritants: TICE Taxol, Hyaluronidase ifosfamide, Hyaluronidase cisplatin, Sodium thiosulfate etoposide Hyaluronidase

Answer 66

11q22-23 Etoposide caused therapy-related leukemia is a chromosomal rearrangement involving the MLL gene on chromosome 11q23 ## Footnote Total cumulative Dose above 2.0g/m2 associated with Leukemia

Answer 67

Hotflashes and osteoporosis Anastrazole-asthenia Letrozole-hot flashes, arthralgias

Answer 68

CHF - need echo before treatment

Answer 69

Bind tubulin, preventing microtubule polymerization during assembly of the mitotic spindle apparatus --> resulting in mitotic arrest “spindle poison” UTD: **M and S phase specific** Chi: M and G2

Answer 70

Notes say: Constipation Chi: Nausea 38%, constipation 31% DLT: BM suppression

Answer 71

1) Hepatic 2) Vesicant - HEAT and hyaluronidase

Answer 72

Selective 5HT3 antagonist (blocks serotonin)

Answer 73

1) Neurokinin-1 antagonist 2) Hepatic cp450

Answer 74

These drugs are also metabolized by cp450: Warfarin - increased INR Cyclophosphamide - increased toxicity Steroids - increased corticosteroid levels (need to reduce dose if premedicating)

Answer 75

* blocks dopaminergic receptors in the brain * alpha-adrenergic blocking effect * competes with histamine for the H1-receptor * muscarinic-blocking effect may be responsible for antiemetic activity

Answer 76

1) Dopamine antagonist 2) Extrapyramidal symptoms (EPS) [akathisia, dystonia, tardive dyskinesia, Parkinsonism] - treat with benadryl Also enhances response to acetylcholine of upper GI tract causing enhanced motility and accelerated gastric emptying

Answer 77

SERM - binds estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects

Answer 78

Osteoporosis - tamoxifen is protective for BMD for post-menopausal patients

Answer 79

Increased LDL Ovarian cysts - 3% **Decreased** LDL [increases HDL and triglycerides. Lowers LDL vs AI, which raises LDL!] Uterine neoplasm < 1% VTE < 1%

Answer 80

Decreases phosphorylation of MTOR, so it is not activated. Prevents subsequent overexpression of oncogenes.

Answer 81

Rapamycin, Temsirolimus, Everolimus **G1 phase specific**

Answer 82

Vincristine Highly emetic (>90%) - Cisplatin - Anthracycline and cyclophosphamide - Cyclophosphamide >=1500 mg/m² Minimally emetic (<10%) - Bev - Bleo - Nivo, pembro - Trastuzumab - Vinblastine, vincristine, vinorelbine

Answer 83

High >90% Moderate 30-90% Low 10-30% Minimal < 10%

Answer 84

Cisplatin, high-dose cyclophosphamide (>1500mg/m2), dacarbazine, anthracycline/cyclophos combo | Angela's listed doxorubicin and ifos but these are moderate risk

Answer 85

Carbo, anthracyclines (doxo, dauno, epi-rubicin), ifosfamide, oxaliplatin, temozolamide, trabectidin | Angela also says: ACT-D, megadoses of MTX, melphalaln

Answer 86

Docetaxel, etoposide, 5FU, gemcitabine, methotrexate, nab-paclitaxel, paclitaxel, PLD, pemetrexed, temsiroliums, topotecan Skinny: Taxanes, folate antagonists / anti metabolites, Topoisomerase inhibitors, temsirolimus, doxil

Answer 87

Bleomycin, bevacizumab, vincas, trastuzumab, monoclonal antibodies (other -mabs)

Answer 88

Ifosfamide, cyclophosphamide, topotecan

Answer 89

Vinca (dose-limiting), taxol, cisplatin (dose-limiting) JS- Chi states cis DLT is nephrotoxicity

Answer 90

Dose-limiting neurotoxicity

Answer 91

mitomycin C, doxorubicin, dactinomycin, vinca alkaloids ## Footnote Can also use DAMN TV for Nitrogens and Trabectedin

Answer 92

Vincas and taxol | *only these per UTD label

Answer 93

cyclophosphamide, gemcitabine, mitomycin C, ifosfamide, capcitabine, irinotecan, 5-FU

Answer 94

Melphalan, etoposide, cyclophosphamide, nitrosureas, chlorambucil, alkylators **melphalan** is most leukemogenic | Etoposide - 11q23 mutation

Answer 95

Nitrosureas: CCNU, BCNU, DTIC (carmustine and lomustine) Also topotecan, niraparib, ipilimumab, nivolumab (ipi and nivo bind peripheral T cells and cross), cyclophos/ifosphamide, Bev, temezolamide

Answer 96

topotecan irinotecan

Answer 97

doxorubicin, mitoxantrone, etoposide, teniposide

Answer 98

Chi: Capecitabine > 5-FU, Doxil, pemetrexed Also Multitargeted tyrosine kinase inhibitors sorafenib, sunitinib

Answer 99

MTX, Adriamycin, cisplatin, etoposide "MACE"

Answer 100

Doxorubicin

Answer 101

Bone pain, followed by fever

Answer 102

cisplatin “MDR1 has at least three major areas where its activity impacts clinical outcomes and toxicity. First, MDR1 confers resistance to cancer chemotherapeutic agents and is a major cause of treatment failures. Because MDR1 transports a wide range of chemotherapy drugs, such as the anthracyclines, vinca alkaloids, taxanes, etoposide, mitoxantrone, bisantrene, and the histone deacetylase inhibitor depsipeptide”

Answer 103

P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs. Significance MDR1 has at least three major areas where its activity impacts clinical outcomes and toxicity. First, MDR1 confers resistance to cancer chemotherapeutic agents and is a major cause of treatment failures. Because MDR1 transports a wide range of chemotherapy drugs, such as the anthracyclines, vinca alkaloids, taxanes, etoposide, mitoxantrone, bisantrene, and the histone deacetylase inhibitor depsipeptide

Answer 104

Gemcitabine, Bleomycin

Answer 105

mTOR (everolimus, temserolimus), tamoxifen ## Footnote Act-D max kiling in G1 but NOT cell cycle specific

Answer 106

Etoposide, Bleomycin

Answer 107

5FU, capecitabine, MTX

Answer 108

Vincas, Taxol, (and Radiation) Vincas: both M and S

Answer 109

Actinomycin D, doxorubicin (Adria), gemcitabine Think: It was AAGonizing going through radiation once, I don’t want to recall it again!

Answer 110

PRA and PRB: Chromosome 11q22-23

Answer 111

Topotecan Etoposide Cyclophosphamide Ifosfamide Temozolamide Lomustine Carmustine Nivolumab (bound to T cells) Ipilimumab (bound to T cells)

Answer 112

Docetaxel has: - LESS neuropathy - MORE fluid retention / peripheral edema (must give extra steroids) - Caution in diabetics due to need for extra steroids

Answer 113

Nab-paclitaxel is albumin bound. It does not contain crempahor (also known as kolliphor - polyoxyethylated castor oil), which is the agent responsible for hypersensitivity reactions.

Angela's Chemotherapy Flashcards

(146 cards)