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Drugs for Heme Malignancies Flashcards

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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
induction therapy for ALL
corticosteroids + vincristine + anthracycline
26
IT MTX
injecting methotrexate into the CNS compartment
27
why do you use IT MTX for ALL?
cancer drugs cannot access the CNS compartment ("sanctuary") --> CNS prophylaxis
28
consolidation therapy for ALL
MTX + mercaptopurine
29
Imatinib
tx of ph chromosome 9;22
30
indications for Imatinib
ALL and CML
31
MOA of Imatinib
tyrosine kinase inhibitor --> prevents proliferative signaling from this receptor
32
Imatinib toxicities
GI (nausea), elevation in hepatic enzyme levels, carious cytopenias
33
Imatinib resistance
mutation in ATP binding site of tyrosine kinase
34
CML chronic phase - 1st line tx
Imatinib
35
cute phase
classical CTX agents
36
2nd generation TKIs
nilotinib, dasatinib
37
advantage of 2nd generation TKIs
nilotinib, dasatinib - retain activity in mutant clones (TK) that have alterations in ATP binding site
38
methods of resistance (besides ATP bidning site mutation)
MDR-1 - pushes out small molecular drugs, TKIs can be substrates for this efflux pump downstream mutation, past receptor (drug won't work)
39
Interferon alfa 2
acts on endogenous receptors, MOA of anticancer function not well known,
40
CLL therapy
fludarabine + cyclophosphamide + rituximab
41
Bendamustine
antimetabolite and alkylating agent
42
MOA of Bendamustine
DNA cross linking - single and double strand breaks
43
Bendamustine advantges
seems less susceptible to resistance
44
CLL treatment complications (3)
opportunisitic infections, anemia (from hemolysis) and hyperuricemia
45
tx for opportunistic infections
prophylactic antibiotics
46
tx for anemia
EPO
47
tx for hyperuricemia
allopurinol
48
tx for Hodgkin lymphoma
treated by combinations of drugs - anthracycline (doxo), mitotic spindle inhibitor (vincristine), and alkylating agent (cyclo or bleomycin) and DHFR inhibitor
49
do you ever use just one drug for Hodgkin?
no - always combos of drugs, more than 2
50
what rule of combinations does Sweatman love?
diff MOAs from drugs in combo --> decrease likelihood of resistance
51
Non-Hodgkin lymphoma - low stage disease - tx
COMP - cyclo + vincristine + MTX + prednisone --> admin for 6 mos
52
adv effects of non-Hodgkin tx (delayed tx effects)
treatment induce secondary malignancy (always a possibility) - others that we didn't really talk about in class
53
two other drugs for CD20 targeted theray
Tositumomab, Ibritumomab
54
additional function of Tositumomab, Ibritumomab
MAbs that carry radioactivity to CD20 positive cells - local delivery
55
I131 labeled anti-CD20 Ab
Tositumomab
56
Y90 labeled anti-CD20 antibody
Ibritumomab
57
Tositumomab
I131 labeled anti-CD20 antibody
58
Ibritumomab
Y90 labeled anti-CD20 antibody
59
side effects of Tositumomab
iodine labeled Ab --> thyroid problems
60
side effects of both Tositumomab, Ibritumomab
generally well tolerated except for expected heme toxic - thrombocytopenia, neutropenia, anemia
61
Chemo and Pregnancy
in utero drug exposure can have number of consequences - teratogenic - structural malformations or in utero death
62
chemo fog
decrease CNS functionality following long term chemo --> drugs cause release of cytokines from periphery that produce CNS deficits
63
Pegasparagase - potential thypersensitivity
product of Erwinia - ppl w/ Erwinia hypersensitivity cannot receive it
64
Pegasparagase other side effects
affects protein C and protein S - problems with bleeding - secondary adverse effect
65
corticosteroids
jekyl and hyde drugs - best anti-inflammatory we have, but metabolic problems
66
corticosteroids metabolic problems
weight gain, water retention, inc blood sugar levels, inc some other blood levels
67
bleomycin
lung/pulmonary toxicity
68
platinum drugs
kidney toxicity
69
chlorambucil
secondary malignancies, aplastic anemia, bone marrow suppression, infertility
70
Anthracyclines - big red flag
cardiotoxicity - dose limiting
71
vincas
peripheral neurotoxicity - drugs acting on microtubules - stocking glove
72
arsenic trioxide
APML differentiation syndrome, AV block, cardiac arrhythmias, leukocytosis
73
ATRA
APML differentiation syndrome, leukocytosis
74
busulfan
bone marrow suppression, secondary malignancies
75
carboplatin
anemia, infection, pregnancy
76
dacarbazine
hepatic disease, secondary malignancy, pregnancy
77
all the rubicins (anthracyclines)
heart disease, hepatic disease, extravasational necrosis
78
Fludarabine
coma, seizures, don't give w/ pentostatin
79
Interferon Alfa-2b
dont give with autoimmune disease, cardiac disease; increased suicidal ideation, depression
80
MTX
ascites, diarrhea, exfoliative dermatitis, pulmonary problems, renal impairment, stomatitis
81
vincas
extravasation, IT admin = fatal, neuropathic toxicity
82
nilotinib
contraindicated in hypokalemia and hypomagnesemia; QT prolongation
83
Ibritumomab,
bone marrow suppression, exfoliate dermatitis, infusion reaction
84
Tositumomab
iodine hypersensitivity, thrombocytopenia, neutropenia
85
rituximab
exfoliate dermatitis, infusion rxn, progressive multifocal leukoencephalopathy

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