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HEME > Drugs for Heme Malignancies > Flashcards

Drugs for Heme Malignancies Flashcards

1
Q

induction therapy

A

high dose combination chemotherapy

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2
Q

consolidation therapy

A

repetition of induction therapy during remission - induction therapy only works against cells that are proliferating, consolidation therapy is to catch any cells that may have been in G0 at the time of induction

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3
Q

maintenance therapy

A

long term, lower dose therapy during remission

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4
Q

Hormesis

A

CTX designed to kill tumor cells, but the biphasic dosing typical of traditional regimens can cause stimulation of tumor cell proliferation at the low dose phase

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5
Q

metronomic dosing and effect on hormesis

A

may avoid the effects of hormesis

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6
Q

metronomic dosing definition

A

daily admin of much lower drug doses (as opposed to dosing intermittently w/ high drug doses - traditional regimens)

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7
Q

metronomic dosing methodology

A

try to increase the amount of time that the drug is putting pressure on the tumor - help counter continued proliferation of tumor cell population - also has effect on immune system

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8
Q

Metronomic dosing effect on tumor microenvironment

A

metronomic dosing has effect on immune system as well as some decrease of vasculature - so in addition trying to kill the tumor cells, you make the environment around the tumor shitty so it is hard for the tumor to live

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9
Q

adaptive therapy

A

gradually decreasing metronomic dosing - induce lifetime-control rather than complete eradication

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10
Q

drugs that have effects on Treg cells

A

anthracycline, taxanes, cyclophosphamide

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11
Q

what are the effects of these drugs on Treg cells

A

anthracyclines, taxanes, cyclophosphamide –> decrease numbers and inhibit the suppressive functions of Treg cells

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12
Q

potential problems with metronomic dosing with regards to infancy

A

angiogenesis - very important to growing infant b/c neovascularization of growing organ is vial fo full development of organ

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13
Q

metronomic dosing - potential problems with long term use (2)

A

long term use could cause
dose related toxicities
treatment related secondary malignancies

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14
Q

metronomic dosing most common problems

A

grade 1 N/V, grade 1 and 2 anemia, neutropenia, leukopenia, and lymphopenia

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15
Q

metronomic dosing - 1 unusual problem

A

subdural hematoma

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16
Q

most common drug regimen for AML (3 part combo)

A

ARA-C + Daunorubicin + Thioguanine

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17
Q

difference for use indication of doxorubicin vs daunorubicin

A

doxorubicin - solid tumors

daunorubicin - blood cancers

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18
Q

AML post remission therapy

A

ARA-C

radiation + autologous transplant - sometimes

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19
Q

Acute Promyelocytic Leukemia indicated treatment

A

ATRA and/or arsenic

not sure if both together or either or

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20
Q

remission and consolidation therapy for APML

A

ATRA + anthracycline + cytarabine

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21
Q

common theme of combination chemotherapy

A

anthracycline (doxo, etc) + cytarabine (can add others)

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22
Q

can complete remission of APML occur w/ ATRA alone?

A

yup

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23
Q

maintenance therapy for APML

A

ATRA + 6-mercaptopurine + MTX

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24
Q

arsenic trioxide - adv effects

A

CV toxicities –> AV block (this is bad.. and unusual side effect for anticancer drugs)

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25
Q

induction therapy for ALL

A

corticosteroids + vincristine + anthracycline

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26
Q

IT MTX

A

injecting methotrexate into the CNS compartment

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27
Q

why do you use IT MTX for ALL?

A

cancer drugs cannot access the CNS compartment (“sanctuary”) –> CNS prophylaxis

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28
Q

consolidation therapy for ALL

A

MTX + mercaptopurine

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29
Q

Imatinib

A

tx of ph chromosome 9;22

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30
Q

indications for Imatinib

A

ALL and CML

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31
Q

MOA of Imatinib

A

tyrosine kinase inhibitor –> prevents proliferative signaling from this receptor

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32
Q

Imatinib toxicities

A

GI (nausea), elevation in hepatic enzyme levels, carious cytopenias

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33
Q

Imatinib resistance

A

mutation in ATP binding site of tyrosine kinase

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34
Q

CML chronic phase - 1st line tx

A

Imatinib

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35
Q

cute phase

A

classical CTX agents

36
Q

2nd generation TKIs

A

nilotinib, dasatinib

37
Q

advantage of 2nd generation TKIs

A

nilotinib, dasatinib - retain activity in mutant clones (TK) that have alterations in ATP binding site

38
Q

methods of resistance (besides ATP bidning site mutation)

A

MDR-1 - pushes out small molecular drugs, TKIs can be substrates for this efflux pump
downstream mutation, past receptor (drug won’t work)

39
Q

Interferon alfa 2

A

acts on endogenous receptors, MOA of anticancer function not well known,

40
Q

CLL therapy

A

fludarabine + cyclophosphamide + rituximab

41
Q

Bendamustine

A

antimetabolite and alkylating agent

42
Q

MOA of Bendamustine

A

DNA cross linking - single and double strand breaks

43
Q

Bendamustine advantges

A

seems less susceptible to resistance

44
Q

CLL treatment complications (3)

A

opportunisitic infections, anemia (from hemolysis) and hyperuricemia

45
Q

tx for opportunistic infections

A

prophylactic antibiotics

46
Q

tx for anemia

A

EPO

47
Q

tx for hyperuricemia

A

allopurinol

48
Q

tx for Hodgkin lymphoma

A

treated by combinations of drugs - anthracycline (doxo), mitotic spindle inhibitor (vincristine), and alkylating agent (cyclo or bleomycin) and DHFR inhibitor

49
Q

do you ever use just one drug for Hodgkin?

A

no - always combos of drugs, more than 2

50
Q

what rule of combinations does Sweatman love?

A

diff MOAs from drugs in combo –> decrease likelihood of resistance

51
Q

Non-Hodgkin lymphoma - low stage disease - tx

A

COMP - cyclo + vincristine + MTX + prednisone –> admin for 6 mos

52
Q

adv effects of non-Hodgkin tx (delayed tx effects)

A

treatment induce secondary malignancy (always a possibility) - others that we didn’t really talk about in class

53
Q

two other drugs for CD20 targeted theray

A

Tositumomab, Ibritumomab

54
Q

additional function of Tositumomab, Ibritumomab

A

MAbs that carry radioactivity to CD20 positive cells - local delivery

55
Q

I131 labeled anti-CD20 Ab

A

Tositumomab

56
Q

Y90 labeled anti-CD20 antibody

A

Ibritumomab

57
Q

Tositumomab

A

I131 labeled anti-CD20 antibody

58
Q

Ibritumomab

A

Y90 labeled anti-CD20 antibody

59
Q

side effects of Tositumomab

A

iodine labeled Ab –> thyroid problems

60
Q

side effects of both Tositumomab, Ibritumomab

A

generally well tolerated except for expected heme toxic - thrombocytopenia, neutropenia, anemia

61
Q

Chemo and Pregnancy

A

in utero drug exposure can have number of consequences - teratogenic - structural malformations or in utero death

62
Q

chemo fog

A

decrease CNS functionality following long term chemo –> drugs cause release of cytokines from periphery that produce CNS deficits

63
Q

Pegasparagase - potential thypersensitivity

A

product of Erwinia - ppl w/ Erwinia hypersensitivity cannot receive it

64
Q

Pegasparagase other side effects

A

affects protein C and protein S - problems with bleeding - secondary adverse effect

65
Q

corticosteroids

A

jekyl and hyde drugs - best anti-inflammatory we have, but metabolic problems

66
Q

corticosteroids metabolic problems

A

weight gain, water retention, inc blood sugar levels, inc some other blood levels

67
Q

bleomycin

A

lung/pulmonary toxicity

68
Q

platinum drugs

A

kidney toxicity

69
Q

chlorambucil

A

secondary malignancies, aplastic anemia, bone marrow suppression, infertility

70
Q

Anthracyclines - big red flag

A

cardiotoxicity - dose limiting

71
Q

vincas

A

peripheral neurotoxicity - drugs acting on microtubules - stocking glove

72
Q

arsenic trioxide

A

APML differentiation syndrome, AV block, cardiac arrhythmias, leukocytosis

73
Q

ATRA

A

APML differentiation syndrome, leukocytosis

74
Q

busulfan

A

bone marrow suppression, secondary malignancies

75
Q

carboplatin

A

anemia, infection, pregnancy

76
Q

dacarbazine

A

hepatic disease, secondary malignancy, pregnancy

77
Q

all the rubicins (anthracyclines)

A

heart disease, hepatic disease, extravasational necrosis

78
Q

Fludarabine

A

coma, seizures, don’t give w/ pentostatin

79
Q

Interferon Alfa-2b

A

dont give with autoimmune disease, cardiac disease; increased suicidal ideation, depression

80
Q

MTX

A

ascites, diarrhea, exfoliative dermatitis, pulmonary problems, renal impairment, stomatitis

81
Q

vincas

A

extravasation, IT admin = fatal, neuropathic toxicity

82
Q

nilotinib

A

contraindicated in hypokalemia and hypomagnesemia; QT prolongation

83
Q

Ibritumomab,

A

bone marrow suppression, exfoliate dermatitis, infusion reaction

84
Q

Tositumomab

A

iodine hypersensitivity, thrombocytopenia, neutropenia

85
Q

rituximab

A

exfoliate dermatitis, infusion rxn, progressive multifocal leukoencephalopathy

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