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Health 32 > Cancer (treatment) > Flashcards

Cancer (treatment) Flashcards

1
Q

Drug treatment of cancer….

main treatment of cancer?

A

cytotoxics (chemotherapy) - most abundant in BNF

also have:
- targeted therapies
- antibodies
- immune therapies
- hormonal therapies

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2
Q

3 types of cytotoxic chemo?

A

alkylating agents and nitrosureas
antimetabolites
natural products

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3
Q

ifosfamide, cyclophosphamide, melphalan, chlorambucil, cisplatin, carmustine
are all examples of what type of chemo drugs?

A

alkylating agents and nitrosureas

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4
Q

How do alkylating agents work?

A

Cross-link DNA strands and inhibit protein synthesis and DNA synthesis

though addition of alkyl group to nucleic acids/proteins/DNA
= inaccurate DNA replication = increase mutations or cell death at any time of cell cycle

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5
Q

2 types of cross linking reactions that may be a result of alkylating agents/ nitrosureas, that will -> strand breaking or substitution reactions?

A

inter (within)
intrastrand (between strands)

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6
Q

why can alkylating agents + nitrosureas act at any point of cell cycle?

A

as targeting DNA directly

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7
Q

what are the 2 main side effects of alkylating agents and nitrosureas?

A

teratogenic and carcinogenic

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8
Q

most alkylating agents are bi or monofunctional?

A

bifunctional (2 alkylation products)

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9
Q

(name 5 sub classes of alkylating agents)

A

a) Nitrogen mustards
b) Alkyl sulfonates (e.g. busulfan)
c) Triazines (e.g. dacarbazine, temozolomide)
d) Nitrosoureas (e.g. carmustine, lomustine)
e) Metal salts

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10
Q

what is mechlorethamine?
state its properties (PK, problems)

A

a nitrogen mustard aka Mustine

rarely used
short half life
very corrosive = toxic
tissue damage: give IV fast
nausea and vomiting SE

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11
Q

whats mechlorethamine used to treat?

A

hodkins lymphoma

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12
Q

Why are nitrogen mustards rarely used for cancer therapy? 3 SE

A

myelosuppressive

corrosive

toxic

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13
Q

What is melphalan (hows it diff to mechlorethamine)?

A

2x Cl groups on end instead of CH3.

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14
Q

How is melphalan administered and why?

A

IV and oral as stable
as preconditioning pre-transplant

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15
Q

What is melphalan used to treat?

A

Multiple myeloma
cancer of plasma cells: mature B cell that produces antibodies

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16
Q

What is the risk with prolonged use of melphalan?

A

myelodysplasia

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17
Q

What is cyclophosphamide? type of drug, MoA

A

alkylating agent produg that is converted to its active form in the liver.

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18
Q

the 2 cytotoxic metabolites of cyclophosphamide?

A
  1. aldophosphamide
  2. phosphamide mustard (+ acrolien)
    (carboxyphosphamide)
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18
Q

with cyclophosphamide, px at risk of haemmorhagic cystitis (bladder inflamm and bleeding) why?

A

acrolein a bladder irritant is produced as metabolite

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19
Q

What is bendamustine used to treat?

A

chronic lymphocytic lymphoma

Non-hodgkin’s lymphoma

(CLL, indolent NHL) better tolerated than R-CHOP

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20
Q

Give 3 examples of metal salts

A

Cisplatin

Carboplatin

Oxaliplatin

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21
Q

How do metal salts work?

A

They inhibit DNA synthesis, through the formation of intra- and inter- strand cross links.

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22
Q

cisplatin has severe SEs, name 3

A

nephrotox
neurotox
ototox

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23
Q

What do metal salts bind to in DNA?

A

guanine groups

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24
Q

cisplatin t1/2 short or long?

A

long terminal t1/2 of 60h

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25
Q

How do antimetabolites work?

A

Works by inhibiting DNA synthesis and protein synthesis.

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26
Q

antimetabolites exert cytotoxic effect through structural + functional similarity to natural metabolites in nucleic acid synth. cell mistakes them for normal metabolites resulting in what 2 possible outcomes?

A

inhibition of critical enz in nucleic acid synth
or
incorporated into nucleic acid -> incorrrect codes, cell death

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27
Q

what is the antidote for acrolein? and how?

A

MESNA
mops up the acrolein

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28
Q

What phase in the cell cycle do antimetabolites target?

A

S phase
as both mechanisms -> inhibition of DNA synth + cell death

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29
Q

examples of anti-metabolites?

A

folate antagonists
pyrimidine analogues
purine analogues
ribonucleotide reductase inhibitors

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30
Q

MOA of 5-FU drug?

A

= pyrimidine analogue that can be misincorporated into RNA and DNA in place of uracil or thymine

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31
Q

what enzyme does 5FU inhibit?

A

activated in vivo + inhib
thymidylate synthase (important for pyrimidine synth. dUMP -> dTMP)

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32
Q

what enzyme does MTX inhibit?

A

DHFR
important in folate cycle: DHF -> THF

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33
Q

What happens to folate in normal cells?

A

Reduced to dihydrofolate and then tetrahydrofolate needed for thymidine and purine synthesis.

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34
Q

How do folate antagonists work?

A

Competitively inhibit DHFR and therefore inhibit thymidine and purine (nucleotide) synthesis.

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35
Q

Mechanism of action for methotrexate? simple

A

Inhibits dihydrofolate reductase, leading to the inhibition of DNA and RNA synthesis.

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36
Q

name 3 examples of folate antagonists?

A

MTX
pemetrexed
raltitrexed

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37
Q

MTX affinity for DHFR enz is 100,000x that of what?

A

folic acid

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38
Q

How can the block caused by methotrexate be overcome?

A

Folinic acid

(form of THF, bypasses the block. given w MTX in practise as rescue for healthy cells)

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39
Q

What is the consequence of the production of excess dihydrofolate reductase?

How can it be overcome?

A

methotrexate resistance

increase the dose (escalation, seen in practise)

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40
Q

4 Clinical indications of methotrexate in cancer

A

osteosarcoma

breast cancer

lymphoma

acute lymphoblastic leukaemia ALL

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41
Q

What toxicities can MTX use cause? 3 MTX SEs

A

Myelosuppression
Mucositis
Renal

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42
Q

how is MTX cleared?

A

renally (up to 80% unchanged in urine)

so urine pH checked by nurses before admin.

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43
Q

when is folic acid prescribed w MTX?

A

alternate days to MTX dose
one per day or once a week

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44
Q

esp w higher doses of MTX, why do we need alkalisation of urine (pH>7) and vigorous hydration?

A

in neutral/ acidic env, MTX will crystallise out in renal tubules can -> kidney damage :(

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45
Q

what the terminal t1/2 of MTX?

A

8-10h but may inc to 24-36h if 3rd space accumulation (pleural/peritoneal effusion) :(

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46
Q

What drug interactions must be considered when prescribing MTX?

A

aspirin/ciprofloxacin/NSAIDs reduce tubular secretion of MTX, can inc MTX levels and tox

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47
Q

what is leucovorin/folinic acid? and role?

A

form of THF
maintain normal cell functions - reverses MTX toxicity

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48
Q

Why is folinic acid given to patients?

A

so healthy cells have enough folate to maintain normal cell functions.
reverses mucositis and myelosuppression

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49
Q

leucovorin/folinic acid may be given to reverse toxic effects of MTX, preferentially in healthy cells over cancer cells as cancer cells commonly have what?

A

lower levels of RFC- reduced folate carrier, needed for cell uptake

  • lower conc will accumulate in cancer cells v healthy tissue
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50
Q

why do you need less folinic acid to neutralise MTX in cancer cells (vs healthy)?

A

cancer cells have less RFC = less effective at taking up folinic acid so need less

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51
Q

if giving rescue treatment (leucovorin/folinic acid) after chemo, wont it rescue cancer cells too?

A

no bc of differentials in uptake of folinic acid ! (RFC)

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52
Q

What are pyramidine analogues?

A

“fradualent” nucleotides
cytosine, thymine, uracil

-> mimic thus interfere w DNA synth

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53
Q

3 examples of pyrimidine analogues?

A

5-fluorouracil (5-FU),
gemcitabine,
capecitabine - erratic oral absorption

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54
Q

what is the prodrug of 5FU?

A

capecitabine

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55
Q

how does 5-FU work?
(pyrimidine analogue)

A

Activated to 5-F-dUMP, which inhibits thymidylate synthase!

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56
Q

How can the activity of 5-FU be enhanced?

A

Co-administer folinic acid to stabilise the complex

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57
Q

What is 2nd activated form of 5-FU and what does it do?

A

5-FUTP which inhibits RNA synthesis

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58
Q

How is 5-FU given?

A

prolonged IV infusions due to short half life (15mins)

also as its working in S phase

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59
Q

what PK parameter of 5FU led to interest in oral analogues eg capecitabine?
(IV preferred)

A

v erratic oral absorption (3-90%)

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60
Q

What were the 5 principal uses of 5-FU?

A

colorectal

breast

stomach

oesophagus

head and neck

(anything GIT)

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61
Q

for phase specific drugs, what type of infusions more beneficial?

A

LONG infusions as it maximises exposure.
if alkylating agents (target cells @ any point in cell cycle) doesnt matter how u give it

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62
Q

What is capecitabine?

A

oral prodrug of 5-FU
undergoes enz conversions to 5-FU in liver and tumour cells

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63
Q

clinical uses of capecitabine?

A

CRC
breast
gastric
pancreatic cancer
biliary

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64
Q

What toxicity can capecitabine cause?

A

Palmar Plantar Erythema PPE

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65
Q

is capecitabine or 5-FU better?

A

capecitabine better tolerated
but experience more hand and foot syndrome: SE

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66
Q

How is capecitabine activated? ()

A

3 step enzymatic conversion to 5-FU.

First 2 steps in liver

Last step in tumor by enzyme thymidine phosphorylase !!

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67
Q

Apart from capecitabine, name two other pyrimidine analogues

A

Gemcitabine

Cytarabine

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68
Q

gemcitabine is converted to gemcitabine triphosphate which in incorporated into DNA in place of deoxycytidine triphosphate.

how often given and for what cause?

A

weekly
pancreatic, NSCLC, bladder, breast cancer

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69
Q

Cytarabine = analogue of cytidine and is converted to active form, ara-CTP which inhibits DNA polymerase.

May also be directly incorporated into DNA chain, preventing replication and making it more susceptible to degradation.

what cancers is it used it?

A

Most useful in tumours with high growth fraction, and mainly used for AML, ALL and certain lymphomas.

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70
Q

2 examples of purine analogues?

A

6-mercaptopurine

fludarabine

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71
Q

purine analogues can be incorporated into growing DNA chain in place of what?

A

natural nucleotides: A, G

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72
Q

what does 6 mercaptopurine do?

A

It blocks de novo purine synthesis

(inhibits various metabolic reactions including purine biosynthesis)

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73
Q

6-mercaptopurine is given orally as maintenance therapy for what cancer?

A

ALL

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74
Q

How is 6-mercaptopurine metabolized?

What caution must be considered?

A

Metabolised to its inactive form in liver by xanthine oxidase.

Caution with allopurinol

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75
Q

What is a prodrug of 6-mercaptopurine

A

Azathioprine

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76
Q

what is fludarabine?

A

active triphosphate, 2F-ara-ATP
inhibits variety of enzymes involved in DNA synthesis

ORAL

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77
Q

what is an example of ribonucleotide reductase inhibitor?

A

hydroxycarbamide

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78
Q

What does do hydroxycarbamide do?

A

Inhibits ribonucleotide reductase

Prevents manufacture of the purines and pyrimidines -> decrease in cellular levels of DNA

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79
Q

ribonucleotide reductase = enzyme essential for what?

A

generation of deoxyribonucelotides

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80
Q

hydroxycarbamide may also have what A. effects on DNA?

A

damage DNA directly, and inhibit DNA repair

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81
Q

What is hydroxycarbamide used to treat?

A

Haematological malignancies
- CML, polycythaemia, thrombocythaemia

oral 500mg capsules- dose tailored to response

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82
Q

antimetabolites work best in S phase why?

A

where high cell turnover - GI, haematological cancers

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83
Q

main 2 types of tox with antimetabolites?

A

GI and bone marrow

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84
Q

What are the two main drug classes in mitotic inhibitors?

A

Vinca alkaloids

Taxanes

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85
Q

How do mitotic inhibitors work?

A

Act on microtubules in the cell nucleus and by arresting metaphase, can inhibit mitosis.

M phase specifically

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86
Q

Microtubules are hollow rod like structures made of what?

A

protein tubulin, and they maintain a cells shape.

major part of mitotic spindle thus essential for distributing genetic material in cell division

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87
Q

MICROTUBULE is in dynamic eqm with intracellular pool of TUBULIN.
what drugs inhibit breakdown of microtubules -> tubulin?

A

taxanes

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88
Q

what drugs prevent assembly of microtubules from tubulin

A

vinca alkaloids

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89
Q

Give 2 examples of a vinca alkaloid

A

Vincristine

Vinblastine

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90
Q

How do vinca alkaloids work?

A

Bind to tubulin and prevent microtubule assembly

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91
Q

What dose is vincristine capped at? and why?

A

2mg regardless of weight due to neurotoxic effects

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92
Q

what is vincristine used in?

A

haematology and sarcoma and neuroblastoma

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93
Q

Where is vincristine metabolised? and why to be cautious?

A

liver - caution in liver impairment and w drugs metab via cyp450 system

.. and 70% elim in faeces

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94
Q

How is vincristine administered and why?

A

highly vesicant but IV infusion due to risk of intrathecal admin !!!

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95
Q

main toxicity w vincristine? and what is it caused by?

A

neurotox (typically cumulative) fatal if admin intrathecal!

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96
Q

What is brentuximan vedotin?

A

novel conjugate of anti-CD30 mab and MMAE (vincristine)

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97
Q

role of MMAE? context of brentuximab vedotin

A

inhibits polymerisation of tubulin

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98
Q

Taxanes are poorly water soluble and is formulated with cremaphor oil - what is the risk associated with this?

A

hypersensitivity reactions
(need pre medication)

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99
Q

What cancers are taxanes licensed for?

A

ovarian and advanced breast cancer

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100
Q

What main tox is associated with the use of taxanes?

A

Neutropenia
may be less if given weekly rather than 3 weekly

(also neurotox, alopecia, cardiotox)

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101
Q

Examples of taxanes apart from paclitaxel

A

docetaxel

abraxane

cabazitaxel

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102
Q

what taxane req pre-med with dexamethasone to minimise risk of hypersensitivity reacs and fluid retention?

A

docetaxel

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103
Q

Why is abraxane less likely to cause hypersensitivity?

A

because it is albumin-bound
.. used in pancreatic cancer

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104
Q

what taxane used for metastatic hormone refractory prostate cancer post docetaxel?

A

cabazitaxel

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105
Q

what 2 cancers is trabectedin licensed for?

A

advanced soft tissue sarcoma
relapsed ovarian cancer

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106
Q

topoisomerases are nuclear enzymes that cause what effect to DNA?

A

DNA strand breaks and therefore allows it to unwind during cell division

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107
Q

difference between topoisomerase I and II?

A

Topoisomerase I - causes single nick in DNA

Topoisomerase II - cleaves both strands

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108
Q

What do topoisomerase inhibitors do to the enzyme-DNA complex?

A

stabilise it and prevent re-ligation causing irreversible DNA strand breaks

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109
Q

What stage in the cell cycle do topoisomerse inhibitors target?

A

late S or early G2

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110
Q

what can inhibit topoisomerase II?

A

etoposide

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111
Q

Why is etoposide usually given IV?

A

oral absorption is erratic and BA only approx 50%

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112
Q

etoposide indications?

A

SCLC, testicular tumours, lymphomas
gen reserved for palliative ie advanced lymphoma

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113
Q

as well as standard tox, whats the risk that may occur 2-3yrs after treatment with etoposide?

A

secondary AML

etoposide similar to alk agents but not -> cell death, just mutations

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114
Q

what are 2 examples of topoisomerase I inhibitors?

A

topotecan
irinotecan

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115
Q

what topoisomerase I inibitor is licensed for:
oral: ovarian + cervical canver
IV: SCLC

A

topotecan

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116
Q

what topoisomerase I inibitor is licensed for advanced colorectal carcinoma?

A

irinotecan

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117
Q

What risk is associated with Irinotecan use?

A

Acute cholinergic syndrome (diarrhea, cramping, emesis)
pre-med w atropine: anticholinergic. given to prevent it

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118
Q

major class of antitumour antibiotics?

A

anthracyclines

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119
Q

4 moas of anthracycliens?

A

inhibit topoisomerase II
DNA intercalation
free radical formation
alkylation

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120
Q

what drug class are:
- doxorubicin
- daunorubicin
- idarubicin
- epirubicin ?

A

anthracyclines

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121
Q

What causes cardiotoxicity/ heart failure with the use of anthracyclines?
main SE

A

the formation of free radicals

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122
Q

Why is mitoxantrone (anti-tumour antibiotic) safer to use than anthracyclines?

A

structurally related but
Does not produce free radicals so is less cardiotoxic

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123
Q

mitoxantrone indicated for use in what 3

A

AML
breast
prostate cancers

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124
Q

What is actinomycin D?

How does it work?

A

anti-tumour antibiotic

binds to DNA and inhibits DNA-dependent RNA synthesis. Also inhibits topoisomerase 2.

sarcomas

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125
Q

What is mitomycin C?

How does it work?

A

anti-tumour antibiotic

causes cross-links between complementary DNA strands, which inhibits replication

lung/ intravesically for bladder cancer

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126
Q

why can you only give mitomycin C every 4-6 weeks?

A

causes delayed myelosuppression

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127
Q

What is bleomycin?

How does it work?

A

anti-tumour antibiotic

causes DNA strand scission resulting in fragmentation of DNA

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128
Q

what antitumour antibiotic indicated for testicular cancer, hodkins, NHL and can be gievn pleurally?

A

bleomycin

but risk of cumulative pulmonary tox

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129
Q

What is gemtuzumab ozogamicin?

A

a novel immunoconjugate of an anti-tumour antibiotic and an anti CD33 antibody

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130
Q

How does gemtuzumab ozogamicin work?

A

Binds to cells expressing the CD33 antigen.

Internalization of the conjugate.

Release of the calicheamicin moiety by acid hydrolysis within lysosomes.

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131
Q

Cancer screening…

currently there are screening programmes in the uk for what 3 cancers?

A

breast, cervical and colorectal

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132
Q

cancer screening can be opportunistic or?

A

population based

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133
Q

what is meant by cancer screening?

A

testing healthy people for signs of disease

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134
Q

why is screening done?

A

find cancer at an early stage or prevent deveopment to save lives

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135
Q

are cancer screening programmes the same as the tests a person might have when doctors are making a diagnosis of cancer?

A

no

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136
Q

true or false; cancer screen tests are there to diagnose cancer?

A

false

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137
Q

what makes a cancer suitable for screening?

A

-common, well understood natural history,
-high sensitivity + specificity,
-test acceptable to population,
-healthcare system should be able to cope with downstream impact of positive results,
-**must improve survival **

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138
Q

give one example of a physical test that might be included in a cancer screen?

A

checking skin moles

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139
Q

give one example of a lab test that might be included in screens?

A

PSA measurement
prostate specific antigen

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140
Q

give one example of an immaging procedure that might be part of a screen?

A

breast mammography

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141
Q

give one example of a genetic test that might be part of a screen?

A

BRCA testing
if family hx of breast cnacer

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142
Q

give 4 components that can be included in screening tests?

A

physical exam, lab tests, imaging and genetic tests

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143
Q

usually we should screen people who are at increased risk of disease. list 4 factors that might put someone at an increased risk?

A

family history, genetic mutation, exposure to carcinogens, age

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144
Q

what is the most important driver that increases someones risk of disease?

A

advancing age

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145
Q

true or false: the risk benefit ratio of screening very elderly people may not be clinically worthwhile therefore must be assessed?

A

true

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146
Q

Advantages of cancer screening?

A

Better outcomes.

Less radical therapy needed.

Reassurance .

Savings because therapy is less complex.

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147
Q

Disadvantages of cancer screening?

A

Over-treatment of borderline abnormalities.

False reassurance for pts with false negative results.

Resource costs of screening systems.

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148
Q

what type of trial is ideal to assess a screening programme?

A

large RCT with long follow up

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149
Q

how long is sufficient to adequately assess a screening programme?

A

at least 10 years

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150
Q

what are 3 possible pitfalls from looking at registry data?

A

lead time bias, overdiagnosis, health screenee bias

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151
Q

what is meant by lead time bias?

A

screened patients appear to live longer because survival calculation includes time preceding when cancer would have been picked up clinically

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152
Q

what is understood by overdiagnosis in the context of skewing survival rates?

A

screening picks up cancers that would not have clinically manifested

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153
Q

what is understood by healthy screenee bias?

A

people attending screening may be more likely to display healthy lifestyle behaviours

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154
Q

What aged women are offered breast cancer screening in the UK? and how often?

A

50-70 every 3 years

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155
Q

high risk patients may be eligible for earlier breast cancer screening. What factors might render them high risk?

A

family history, previous chemotherapy for cancer

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156
Q

what x ray is used in breast cancer screens?

A

mammogram

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157
Q

true or false; breast cancer screens do not carry an increased risk of over diagnosis?

A

false

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158
Q

What aged women are offered cervical cancer screening in the UK? and how often?

A

25-64

every 3 years until 49 years then every 5 years

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159
Q

Why is cervical cancer screening not offered for women less than 25?

A

it is rare under this age

might lead to unecessary treatment, abormal cell changes often become normal

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160
Q

the incidence of cervical cancer in the UK is expected to decrease further due to the implenatation of what vaccination programme?

A

HPV

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161
Q

HPV causes the majority of cervical cancer cases with the majority being due to what 2 subtypes?

A

16 and 18

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162
Q

why are women above 65 not routinely offered cervical cancer screens?

A

unlikely to get it

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163
Q

what is the exception which means that women above 65 would be invited to a cervical cancer screen?

A

1 of last 3 tests was abnormal

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164
Q

the screening procedure for cervical cancer involves a small sample of cells being taken from the cervix. What is it first checked for?

A

HPV
if not found, no further tests taken

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165
Q

if certain types of HPV are found in a cervical cancer screen what are the next steps?

A

sample checked for any changes in cervix cells using liquid based cytology

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166
Q

if changes are identified in the cells of the cervix after using liquid based cytology, what procedure are patients invited for?

A

colposcopy

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167
Q

currently in england people between what age range are sent a home bowel cancer test kit every 2 years?

A

60-74

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168
Q

why is the faecal immunochemical test (FIT) to screen for bowel cancer instead of the faecal occult blood test (gFOBT) now?

A

more accurate and easier to use

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169
Q

true or false: NHSE are hoping to lower the bowel screening age to 50 in the future?

A

true

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170
Q

the FIT kit to screen for bowel cancer was introduced in 2019. What does it use to detect human blood in stool?

A

specific antibodies

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171
Q

for people with positive detection of human blood in stool after a FIT test, what will be they offered?

A

colonscopy

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172
Q

give 2 reasons that might explain the significant increase in the incidence of prostate cancer in the past 10 years?

A

ageing population and earlier detection using PSA screening

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173
Q

what improvement is required of the PSA test?

A

help distinguish between aggressive and indolent cancers

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174
Q

Why is prostate cancer not screened for yet? regularly

A

PSA test needs development.

Lack of quality trial data is available.

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175
Q

what may increase PSA levels (above 5) other than prostate cancer?

A

UTI
rigorous exercise before test
drug that interferes w PSA levels

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176
Q

there is no lung cancer screen in the UK however it is recommended in the USA for current or former smokers. What test is used for this screen?

A

annual low dose CT scan

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177
Q

what is rhe role of the pharmacist in cancer screening?

A

encourage people to attend, provide information and reassurance about the process

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178
Q

name some barriers to cervical screening

A

women embarrassed about having smear test
worried about result
concerned about procedure and pain
dont think at risk
unaware of screening

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179
Q

Novel therapies for cancer…

biologic agents/ immuno therapies may be non-specific such as..

A

cytokines like interferon/ immunomodulators like thalidomide

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180
Q

biologic agents/ immuno therapies may be more targeted such as…

A

mabs: rituximab

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181
Q

When might a chronic myeloid leukaemia patient be given extra lymphocytes?

A

after an allogenic stem cell transplant, the patient may relapse and the pt can be given donor lymphocytes to prevent this.

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182
Q

IL2 and interferon a are both examples of what type of biologic?

A

cytokines

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183
Q

which cells produce il2?

A

activated t cells

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184
Q

what is the moa of il 2?

A

stimulates t cell proliferation and activates nk cells

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185
Q

what two types of cancer has il 2 been used in the treatment of?

A

renal cell and melanoma

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186
Q

interferon a have a number of immunomodulatory effects, give some of these?

A

activation of nk cells,
modulation of antibody production,
inducing antigen presentation on tumour cells

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187
Q

list some of the indications, of interferon a other than CML?

A

NHL, renal cell carcinoma and multiple myeloma

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188
Q

why are cytokines given as drug therapy?

A

substances alr part of IS, give in drug form to strengthen IS and have anticancer effect

(rarely used in practaise tho)

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189
Q

thalidomide is an immunomodulator and has a role in the treatment of what type of cancer?

A

multiple myeloma

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190
Q

Drug class of thalidomide?

A

immunomodulator

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191
Q

how does thalidomide work to help treat cancers such as multiple myeloma?

A

inhibits angiogenesis to prevent tumour spread

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192
Q

true or false: newer varients of thalidomide such as lenalidomide and pomalidomide are now being used in the clinic?

A

true

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193
Q

binding of mabs to tumour associated antigens can result in the destruction of tumour cells by what 2 processes?

A

complement activation or ADCC

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194
Q

pembrolizumab and nivolumab are active in many cancers. What do they block to release an immune system ‘break’?

A

PD1 receptor

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195
Q

what is the rationale behind attaching antibodies such as mabs to cytotoxic radioisotopes, toxins or drugs?

A

targeting effect

196
Q

pembrolizumb
nivolumab
atezolizumab
ipilumumab
abatacept

all examples of what class of drug?

A

checkpoint blockade

.. activating IS

197
Q

pembrolizumb and nivolumab inhibit PD1 to treat what cancers..

A

melanoma
lung
bladder
..

198
Q

what does atezolizumab inhibit and treat?

A

PD1
bladder and lung

199
Q

what does ipilumumab inhibit and treat?

A

CTLA4
advanced melanoma

200
Q

abatacept enhances ctla4, true or false?

A

true

201
Q

give two uses for abatacept?

A

RA and kidney transplant rejection

202
Q

where is the CTLA4 receptor found?

A

on T cells

203
Q

effect of antibody binding to CTLA4?

A

(on T cells)
switches off T cell activation

204
Q

2 ways to get negative regulation during effector phase?

A

use mab to block pd1 or pdl1

205
Q

What mab is licensed for:

follicular lymphoma
high grade B cell lymphoma
CLL

A

rituximab/ mabthera

206
Q

rituximab is a monoclonal antibody specific for X and expressed on the surface of mature b cells

A

CD20

207
Q

cd20 is expressed on the surface of which mature cells?

A

B cells

208
Q

give the 3 different ways by which rituximab binding causes cell death?

A

apoptosis induction,
px immune system activation
sensitisation of resistant lymphoma cells to conventional chemo

209
Q

the most common side effects of rituximab are infusion related, give some examples?

A

fevers, chills and rigors

210
Q

why is it important to premedicate prior to giving rituximab? rare SE

A

danger of cytokine release syndrome

211
Q

what drugs can you use to premedicate with before giving rituximab? 3

A

antihistamine, paracetamol, steroids

212
Q

the her-2/ neu antigen is overexpressed on some breast cancer cells. name one antibody drug and brand name that can be used to target this?

A

trastuzumab/ herceptin

213
Q

What cancers is trastuzumab used for?

A

HER +ve breast cancers

214
Q

trastuzumab can be used as monotherapy or in combination with paclitaxel or what other drug, to treat metastatic breast cancer?

A

docetaxel

215
Q

what is the only uk licensed indication for alemtuzumab/ mabcampth?

A

MS

216
Q

what relatively specific antigen for lymphocytes does alemtuzumab (MabCampath) target?

A

CD52

217
Q

What is CAR T cell therapy?

A

Immune therapy against cancer, where the patients own T-cells are harvested, transformed outside the body to express a cancer specific receptor and then rein fused into the patient to target the cancer.

218
Q

(CAR-T)
kymriah, yescarta and tecartus are available in the UK to treat B-ALL, advanced non -hodgkins and mantle cell lymphoma. What protein expressed on b cells do they all target?

A

CD19

219
Q

what is there a very high risk of with kymriah, yescarta and tecartus use?
CAR T therapy

A

cytokine release syndrome CRS
(+ neurological complications)

220
Q

what is the name given to hollow cylindrical structures made from a number of different proteins?

A

proteosomes

221
Q

2 locations where proteosomes are found?

A

nucleus and cytoplasm

222
Q

proteosomes play a key role in the cell and degrade a number of protein substrates. Why is this important?

A

accumulation of proteins is toxic to the cell

223
Q

proteosome inhibitors have become standard treatment for what type of cancer?

A

multiple myeloma

224
Q

what is the drug class of bortezomib?

A

proteosome inhibitor

225
Q

what is the first line drug used to treat multiple myeloma?

A

bortezomib

226
Q

give 3 side effects that are associated with bortezomib?

A

neuropathy, thrombocytopenia and fatigue

227
Q

bortezomib is only licensed for IV bolus admin, true or false?

A

false

SC better, easier and lower risk of neuropaty

228
Q

carfilzomib is a newer proteosome inhibitor and is given as an IV infusion, but is associated with what type of toxicity?

A

cardiac

229
Q

can ixazomib be given orally, yes or no?

A

yes

230
Q

true or false: ixazomib is NICE approved as part of an all oral combination with lenalidomide and dexamethasone?

A

true

231
Q

what class of drugs are known as nibs?

A

protein kinase inhibitors

232
Q

what do nibs target that is different from traditional chemo agents?

A

growth factors and their receptors on individual cancer cells

(instead of DNA -> cell damage)

233
Q

how do nibs differ in their toxicity profiles to traditional chemo agents?

A

less nausea and myelosuppression

234
Q

give a drug class that can be used as a targeted therapy whereby, individual targets mean that there are individual toxicities?

A

protein kinase inhibitors nibs

235
Q

CML is characterised by the 9;22 translocation, what is this chromosome known as?

A

philadelphia

236
Q

the philadephia chromsome on chromosome 22 results in the production of a new fusion gene known as?

A

BCR-ABL

237
Q

what is rhe product of the BCR-ABL fusion gene and why is this a problem?

A

bcr-abl tyrosine kinase which is leukaemogenic

238
Q

name one drug which is used in CML and is a selective inhibitor of bcr-abl kinase?

A

imatinib

239
Q

Mechanism of action of imatinib in chronic myeloid leukaemia

A

binds to BCR-ABL kinase domain by preventing the transfer of a phosphate group to tyrosine on the protein substrate and the subsequent activation of phosphorylated protein.

Blocks proliferative signals to the nucleus, inducing cell apoptosis

240
Q

Common toxicities associated with imatinib

A

haematological, diarrhoea, rash, oedema, nausea, cramps, headache

241
Q

Imatinib is metabolised by CYP3A4 and therefore has many DDIs with what drug type?

A

enzyme inducers

242
Q

name some enzyme inducers that would have DDI with imatinib (cyp3a4 metabolism)

A

itraconazole, clarithrimycin, phenytoin, rifampicin, warfarin, ciclosporin

243
Q

give one mutation which occurs commonly in AML?

A

FLT3

244
Q

how do FLT3 mutations benefit cancer cells?

A

constitutive kinase activation,
promotes growth, survival and anti apoptotic signalling

245
Q

Give an example of a first gen FLT-3 inhibitor - protein kinase inhibitor

A

Midostaurin

246
Q

is midostaurin a first or second generation FLT3 inhibitor?

A

furst

247
Q

what are 3 PARPi that are currently licensed for use in the UK in some capacity to treat ovarian cancer?

A

olaparib, niraparib and rucaparib

248
Q

what are parp enzymes important for?

A

DNA repair

249
Q

what are olaparib and talazoparib licensed for?

A

breast cancer

250
Q

generally PARPi require the prescence of what mutation to exert their action?

A

BRCA

251
Q

What is the role of BCL-2?

A

anti-apoptotic factor

inhibits Bax/Bak

252
Q

BCL-2 is a protein that has key roles in apoptosis and is overexpressed in a variety of cancers, give an example of one where this is the case?

A

CLL

253
Q

cell damage leads to the release of pro apoptotic proteins such as BAX, BID and BAK. How do these proteins lead to apoptosis?

A

promote release of cytochrome c from mitochondria, triggers release of caspase enzymes, drives apoptosis

254
Q

What protein inhibits the following pro apoptotic factors:

BAX, BID, BAK?

A

BCL-2

255
Q

what is the only currently licensed BCL-2 inhibitor?

A

venetoclax

256
Q

what two cancers is the treatment of venetoclax approved for?

A

CLL, AML

257
Q

why is important that venetoclax is started at a low dose and slowly titrated upwards?

A

high risk of tumour lysis syndrome TLS

258
Q

why is venetoclax given with posconazole in AML patients?

A

beneficial DDI

very expensive, posconazole increases exposure so a lower dose can be used

259
Q

VEGF is a key growth factor that promotes what process?

A

angiogenesis

260
Q

why might we want to inhibit angiogenesis of cancer cells in cancer patients by VEGF?

A

can halt tumour growth and spread

261
Q

name a modified antibody that can be used to target/inhibit VEGF in order to stop angiogenesis?

A

afilbercept

262
Q

name a mab that can be used to target VEGF in order to prevent angiogenesis?

A

bevacizumab, ramucirumab

263
Q

name a TKI that can be used to target VGEF and inhibit it in order to stop angiogeneis (commonly in kidney cancer)?

A

sunitinib , axitinib

264
Q

3 types of drugs that can target VEGF? inhibiting angiogenesis

A

MABs
TKIs
modified antibody

265
Q

What is CPX-351?

How does it improve “old” chemo drugs?

A

lipososmal delivery system

enhances uptake
longer half life

266
Q

cpx-351 is a liposomal delivery system that contains what 2 drugs?

A

cytarabine and daunorubicin 5:1 molar ratio

267
Q

why might it be more beneficial to use CPX-351 liposomal formulations to enhance older chemo agents?

A

enhanced marrow conc and improved uptake into AML blasts

268
Q

Drug treatment: clinical and economic…..

Describe the absorption characteristics of most anticancer drugs.

A

poor oral absorption

unstable in gastric acid

269
Q

name one 5FU derivative drug that is given orally?

A

capecitabine

270
Q

what advice would you give to patients taking etoposide or uftoral capsules with regards to food?

A

take before food

271
Q

what advice would you give to patients in relation capecitabine and food?

A

with or after food

prodrug of 5FU

272
Q

why might fat/ water solubuility and degree of protein binding be an important determinant of distribution and therefore have implications for the management of CNS disease?

A

small lipophilic drugs have to be able to cross bbb

273
Q

how are most anticancer drugs metabolised? and where?

A

cytochrome P450 in liver

274
Q

examples of small lipophilic drugs used in CNS disease?

A

MTX!!
cytarabine
BCNU

can cross BBB

275
Q

wherever possible what bw should be used to dose obese patients to ensure that toxicity does not occur?

A

actual bw

276
Q

why might px with liver disease be at risk of increased tox of anti cancer drugs?

A

commonly metabolised by p450 enzymes in liver

277
Q

active drug or metabolites are usually excreted by what organ?

A

kidneys

278
Q

name 3 drugs/ drug classes that can interefere with renal excretion of cytotoxic drugs?

A

mtx, penicillins, nsaids

279
Q

What key cancer drugs need dose reductions in renal impairment?

A

cisplatin
methotrexate

.. carboplatin, bleomycin

280
Q

What key cancer drugs can be nephrotoxic?

A

cisplatin

methotrexate

mitomycin C

281
Q

cisplatin is a nephrotoxic drug, what is it important that is adequate in patients?

A

hydration

282
Q

name 2 drugs where adequate hydration in patients is essential?

A

cisplatin and ifosamide

283
Q

what should be done to a patients urine if they are using high doses of mtx?

A

alkalinse

284
Q

true or false: mitocycin c is a nephrotoxic drug and is associated with haemolytic uremic syndrome?

A

true

285
Q

What key cancer drugs need dose reductions in HEPATIC impairment?

A

doxorubicin

vincristine

paclitaxel

286
Q

What 4 key cancer drugs can be hepatotoxic?

A

nitrosoureas

methotrexate

cytarabine

6-mercaptopurine

287
Q

mtx is hepatoxic, list 2 things that might occur to the liver due to use?

A

fibrosis and cirrhosis

288
Q

why would you see elevated liver enzymes in nitrosoureas and cytarabine?

A

hepatotoxic

289
Q

true or false 6MP is associated with cholestasis and necrosis due to its hepatic toxicity?

A

true

290
Q

what 3 groups can the factors that determine the success of chemotherapy be divided into?

A

objective of treatment,
px factors,
factors related to tumour

291
Q

what type of treatment objective: curing disease or focusing on symptom palliation as adjuvant to surgery, is likely to have aggressive chemo involved?

A

curative on own as best chance of eradicating disease

if adjuvant on top of surgery, be careful as dont want to give highly toxic

292
Q

list 3 patient factors?

A

general medical condition, age, motivation

293
Q

PS is a well known prognostic factor in the treatment of many tumours and stands for performance status, is a good value 0 or 4?

A

0

294
Q

would patients with PS scores of 3-4 be given chemo?

A

no

295
Q

give one reason why children and young adults might tend to respond better to chemo compared to elderly patients?

A

link to decreased organ function (kidneys, bone marrow…) in elderly

296
Q

give 2 things that can determine compliance in patients?

A

psychological status and motivation for treatment

297
Q

list some factors that are related to the tumour that might influence whether chemo is given to patients or not?

A

sensitivity to chemo,
clinical stage and size,
growth characteristics

298
Q

do less differentiated cells tend to be more or less aggressive?

A

more

299
Q

do less differnetiated cells tend to be more or less sensitive to chemotherapy?

A

more

300
Q

true or false: with each new cancer treatment introduced to a patient benefit and chances of success decrease?

A

true

301
Q

is adjuvant chemo for some cancers like breast given before or after surgery or radiotherapy?

A

after

302
Q

What cancers are often curative?

A

ALL and AML (especially in children)

NHL

303
Q

What cancers are more than 30% responsive?

A

breast cancer

small cell lung cancer

multiple myeloma

CLL

304
Q

What cancers are usually highly resistant?

A

non-small cell lung cancer

renal cell carcinoma

pancreatic cancer

305
Q

What is the aim of adjuvant chemotherapy?

A

eradicate micrometastases

(diagnosis of primary cancer but also have other deposits elsewhere, too small to be picked up on scan)

306
Q

why might tumour cell kinetics favour an adjuvant chemo approach to eradicate micrometasteses?

A

higher growth fraction and shorter cell cycle times when tumour burden is low

307
Q

why should the regimen of adjuvant chemo ideally have low tox ?

A

proportion of patients will be cured already

308
Q

is neoadjuvant chemo given before or after surgery is performed?

A

before

309
Q

what is the principle that neoadjuvant chemo is based on?

A

px likely to have undetectable micrometastatic disease at presentation

310
Q

What is neo-adjuvant chemotherapy?

A

Chemo given before surgery to shrink tumour.

311
Q

what are the 3 potential advantages of neo adjuvant therapy?

A

earlier exposure to cytotoxic drugs,
can measure objective response to primary lesion to see likely success,
tumour regression may allow for less extensive surgery

312
Q

what might be the disadvantage of giving neoadjuvant chemo?

A

increased infection risk if become unwell before chemo,
if chemo doesnt work tumour may grow and make surgery harder or impossible

313
Q

why might combination chemo be more successful than a single chemo agent? 3 reasons

A

prevent resistant clones, cytotoxicity to resting and dividing cells, biochemical enhancement of effect

314
Q

true or false: combination chemo should choose individually active drugs?

A

true

315
Q

TRUE OR FALSE: for combination chemo drugs with overlapping toxicities should be chosen?

A

false

316
Q

true or false: for combination chemo agents with different modes should be chosen?

A

true

317
Q

true or false: for combination chemo, drugs should be used at their optimal dose and schedule?

A

true

318
Q

for combination chemo, agents should be chosen that do/do not display cross resistance?

A

do not

esp w P glycoprotein pump- particular issue w natural products

319
Q

why should the treatment free interval be the shortest possible for patients who are on combination chemo regimens?

A

allow recovery of most sensitive host tissue

320
Q

cell cycle phases?

A

M
G1
S
G2

321
Q

cytarabine, 5fu and mtx are all phase specific and work in what phase of the cell cycle?

A

S

322
Q

what phase of the cell cycle does bleomycin work in?

A

G2

323
Q

what phase of the cell cycle does etoposide work in?

A

G2

324
Q

what phase of the cell cycle do vinca alkaloids work in?

A

M

325
Q

what phase of the cell cycle does paclitaxel work in?

A

M

326
Q

give an example (cytarabine) of how phase specifism leads to implications for scheduling?

A

cytarabine in AML given 12 hrly 8-10 days

327
Q

name 2 antibiotics that are cell cycle specific?

A

doxorubicin, epirubicin

328
Q

name 3 alkylating agents that are cell cycle specific drugs?

A

chlorambucil, cyclophosphamide, cisplatin

329
Q

2 types of cell cycle nonspecific drugs

A

nitrogen mustard
nitrosureas: carmusting, lomustine

330
Q

true or false, cytotoxic antibiotics and alkylating agents work at any point in the cell cycle?

A

true

331
Q

although not effective in patients, what is rhe theorectical benefit of nitrogen mustards and nitrosoureas such as carmustine and lomustine being cell cycle non specific drugs?

A

act on cells in and out of cycle so target resting and dividing cells

332
Q

BEP is a combination regimen for testicular cancer is made up of what 3 drugs?

A

bleomycin, etoposide and cisplatin

333
Q

what is the moa of bleomycin?

A

inhibits dna synthesis and arrests cell in G2

334
Q

does bleomycin induce or lack myelosuppression?

A

lack

335
Q

give 2 sites that belomycin is toxic to?

A

skin and mucous membranes

336
Q

which toxicity is most associated with bleomycin:

pulmonary, cardiovascular, renal, hepatic

A

pulmonary

337
Q

what is the drug class for etoposide and what does this mean ?

A

topoisomerase 2 inhibitor important for unwinding dna

338
Q

etoposide is myelosuppressive and can present in patients as?

A

alopecia

339
Q

is etoposide or bleomycin associated with moderate nausea and vomiting?

A

etoposide

340
Q

why is etoposide given slowly/ what is trying to avoided?

A

hypotension

341
Q

cisplatin is an alkyalting agent, what does this mean it does to DNA?

A

cross links

342
Q

which of the following is associated with cisplatin

nephrotox

hepatotox

ototox

neuropathy

cns tox

pulmonary tox

A

nephrotox, ototox, neuropathy

343
Q

is etoposide or cisplatin associated with severe nausea and vomiting?

A

cisplatin

344
Q

which of the following myeloma drugs is associated with neutropenia

thalidomide

bortezomib

lenalidomide

pomalidomide

A

lenalidomide and pomalidomide

345
Q

which of the following drugs is associated with thrombocytopenia

thalidomide

bortezomib

lenalidomide

pomalidomide

A

all except thalidomide

346
Q

which of the following drugs is associated with neuropathy?

thalidomide

bortezomib

lenalidomide

pomalidomide

A

thalidomide and bortezomib

(not L and P)

347
Q

3 of these drugs have a low risk of constipation. with which drug is constipation a definate side effect and more pronounced?

thalidomide

bortezomib

lenalidomide

pomalidomide

A

thalidomide

348
Q

from the following list of drugs diarrhoea is only associated with which drug ?

thalidomide

bortezomib

lenalidomide

pomalidomide

A

bortezomib

349
Q

somnolence is associated with drug from the following list?

thalidomide

bortezomib

lenalidomide

pomalidomide

A

thalidomide

350
Q

which of the following drugs is not associated with thrombotic risk ?

thalidomide

bortezomib

lenalidomide

pomalidomide

A

bortezomib

351
Q

Stem cell transplantation…

the first line treatment for this condition is treatment with ABVD, what is the condition?

A

hodgkins

352
Q

what drugs are part of the ABVD regimen for hodgkins?

A

adriamycin, bleomycin, vinblastine and dacarbazine

353
Q

hodgkins patients are given ABVD every 2 weeks for how many months?

A

4-6

354
Q

if patients relapse or there is no, or partial response to ABVD, what is the second line treatment for hodgkins?

A

different regimens such as IVE and ESHAP

355
Q

What is the 3rd line treatment for hodgkins for both patients who are in remission and those who have had partial or no response?

A

autologous SCT

356
Q

name 2 drugs that would be appropriate for 3rd or 4th line treatment for patients with hodgkins who have relapsed after autologous SCT?

A

brentuximab and nivolumab

357
Q

if a patient is fit enough after 3rd or 4th line treatment for hodgkins, what might be offered?

A

allogeneic SCT

358
Q

is autologous or allogeneic SCT associated with higher risks?

A

allogeneic
as stem cells are from a donor

359
Q

for autologous SCT haematopoetic SC are harvested from the patient and stored. Under general anasthetic, where might the SC be removed from?

A

bone marrow or peripheral blood

360
Q

process of an autologous SCT?

A

haematopoietic stem cells are harvested from the patient and stored.

pt is given high dose chemotherapy.

pt is ‘rescued’ by re-infusing stem cell after chemo.

361
Q

in order for peripheral SC harvest what endogenous hormone are patients given?

A

G-CSF

362
Q

G-CSF injections are given 3-4 days prior to peripheral SC harvest for autologous SCT. What is the rationale behind doing this?

A

drives proliferation of wbc, stimulates stem cells to leave bone marrow and enter peripheral circulation

363
Q

How might SC be removed from a patients peripheral blood for autologous SCT?

A

px hooked to apheresis machine, blood drawn out, enters machine, SC removed, blood returned to the patient

364
Q

after stem cell harvest a high dose of chemo is given to patients. What cancer is BEAM or LEAM used for?

A

lymphoma

365
Q

after stem cell harvest a high dose of chemo is given to patients. What cancer is melphelan used for?

A

myeloma

366
Q

why do most chemotherapy regimens have a ceiling dose?

A

myelosuppression puts the patient at risk of infection as wbc, platelets and rbc are destroyed

367
Q

after high dose chemo in the context of autologous SCT, patients are given rescue therapy. What is this?

A

reinfusing stem cells after chemo

368
Q

what is the rationale behind rescue therapy?

A

px given high dose chemo, to prevent tox px given fresh bone marrow in the form of SC, go from peripheral circulation -> bone marrow and repopulate

369
Q

what is the main difference between autologous and allogeneic SCT?

A

source of allogeneic SCT cells is donor

370
Q

there are different types of allogeneic SCT due to variability in terms of what 3 things?

A

SC source, donor and intensity

371
Q

list some different sources for SC for allogeneic SCT?

A

pb, bone marrow and umbilical cord

372
Q

name some different donors that would be suitable for allogeneic SCT?

A

sibling, stranger, parent, child

373
Q

full intensity is the strongest chemo that can be managed in the context of allogeneic SCT, patients above what age might recieve reduced intensity?

A

45

374
Q

what is the likelihood of a sibling being a suitable donor match for allogeneic SCT?

A

25% (punnett square)

375
Q

why is rejection rare to see in cases of autologous SCT?

A

immune system destroyed and not functioning therefore unable to reject transplant
WBCs wiped out

376
Q

What are the main complications of allogeneic SCT?

A

Graft vs Host disease

Infection

377
Q

what is GVHD?

A

new immune rejects patient and attacks host

378
Q

GVHD can be classed as acute or chronic, what is the difference between the two?

A

acute is 0-100 days and chronic is beyond 100 days

379
Q

3 areas that are commonly affected by GVHD?

A

skin, gut and liver

380
Q

true or false, GVHD affecting the liver is usually only picked up on blood tests, before there is a presenatation of jaundice?

A

true

381
Q

what family of cells drives GVHD?

A

T cells

382
Q

What is cytomegalovirus?

A

herpes virus that majority of theUK are seropositive for

383
Q

Why is allogenic SCT better than autologous SCT?

A

no risk of infusing malignant cells eg myeloma

immune mediated effects….

384
Q

whats the main cause of death in px not cured by allograft?

A

infection
GVHD
over prolonged period… relapse!!

385
Q

what can DLI donor lymphocyte infusions induce in px who relapse after an allograft?

A

remissions

386
Q

T/F
px who develop mild GVHD hane better outcome than px who dont develop it?

A

true

387
Q

are high or low ciclosporin levels associated with improved survival rates?

A

low

388
Q

What is the GVL effect?
graft vs leukemia

A

The new immune system after a SCT can attack and kill any residual cancer cells remaining after the transplant.

389
Q

What immunosuppressants are given to prevent GVHD?
suppress T cells

A

Ciclosporin/ tacrolimus

Methotrexate

Alemtuzumab

Mycophenolate

ATG

390
Q

What drugs are given to treat GVHD?

A

Corticosteroids

391
Q

ciclosporin is the mainstay of CVHD prophylaxis and is used in combination of low doses of what other drug?

A

MTX

392
Q

true or false: ciclosporin is widely used in both solid organ and SC transplants?

A

true

393
Q

how does ciclosporin work to prevent GVHD?

A

suppresses t cell activation via inhibition of calcineurin
(enz important in T cell activation)

394
Q

is ciclosporin usually start the day before or the day after SCT?

A

before -1

395
Q

the starting dose of ciclosporin is 5mg/kg/day as a continous infusion for one day and then, 2.5mg/kg BD over 4 hrs.

Patients might develop flushing, nausea or tremor. What can be done reduce this?

A

slow infusion

396
Q

at what point what you switch iv ciclosporin to oral?

A

once mucositis resolves

397
Q

nephrotox is associated with ciclosporin and may be made worse if used what other nephrotoxic drugs?

A

amphotericin, vancomycin and gentamicin

398
Q

Side effects of ciclosporin

A

nephrotoxicity

hypertension

hypomagnesaemia

hepatotoxicity

neurological syndromes

hirsutism

399
Q

ciclosporin may cause htn. name a drug, dose and its class that can be given to treat this?

A

CCB, amlodipine, 5-10mg

400
Q

hypomagnesaemia is very common with ciclosporin use. what 2 things can be given to patients to treat this?

A

mg aspartate sachets or mg citrate tablets

401
Q

ciclosporin is associated with neurological syndromes, give one way that this might manifest in patients?

A

fits

402
Q

what symptoms are common in patients with ciclosporin but if severe can suggest high levels?

A

anorexia, nausea, vomiting, tremor

403
Q

give 2 symptoms that are associated with prolonged use of ciclosporin?

A

hirsutism and gum hypertrophy

404
Q

How is ciclosporin metabolised?

A

by CYP450 in the liver

405
Q

enzyme inhibitors such as
azoles
clarithromycin
grapefruit juice

will increase/decrease levels of ciclosporin

A

increase

406
Q

enzyme inhibitors such as
phenytoin,
rifampicin,
carbamazepine,
st johs wort

will increase/decrease levels of ciclosporin

A

decrease

407
Q

what enzyme does tacrolimus inhibit to exert its moa?

A

calcineurin

408
Q

true or false: tacrolimus and ciclosporin levels are monitored in patients?

A

true

409
Q

T/F tacrolimus is interchangeable with ciclosporin?

A

true
works in same way

410
Q

mtx is a conventional chemo agent but used in high or low doses to prevent GVHD?

A

low

411
Q

gave one adverse effect that is commonly associated with mtx use?

A

mucositis

412
Q

what is the rationale of giving 3 doses of folinic acid 15mg, starting 12 hrs after mtx?

A

reduce the risk of mucositis SE

413
Q

what 2 actions would be recommended to patients on mtx for GVHD prevention who develop mucositis?

A

consider omitting day 12 dose if severe
or prescribe folinic acid mouthwash

414
Q

what is the moa of mycophenolate?

A

inhibits dna production in lymphocytes

415
Q

true or false: mycophenolate is commonly used in solid organ transplantation?

A

true

416
Q

give 3 side effects associated with mycophenolate use?

A

GI, increased risk of infection, reduced blood count

417
Q

what is alemtuzumab used for in the context of allogeneic SCT?

A

prophylaxis and treatment of GVHD in steroid refractory periods

418
Q

alemtuzumab is a monoclonal antibody against CD?

A

CD52

419
Q

pre medication is required for alemtuzumab and is given slowly over 4 hrs. Why might this be the case?

A

risk of infusion related reactions

420
Q

alemtuzumab dose: 10mg daily from day -5 to -1
or 30mg od from -2 and -1.

why is it given before transplant as well?

A

long t1/2
will hang around for few weeks

421
Q

true or false: alemtuzumab has an increased risk of bacterial, viral and fungal infections

A

true

422
Q

ATG/ALG is anti lymphocyte immunoglobulin and is used to prevent GVHD, What does it do to the number of circulating lymphocytes?

A

reduces

423
Q

true or false: ATG/ALG is derived from rabbits that have been injected with human lymphocytes?

A

true

424
Q

there is also an equine form of ATG/ALG used tot reat what?

A

aplastic anaemia

425
Q

corticosteroids are the first line treatment in GVHD, name 3 suitable agents?

A

prednisolone, methylprednisolone, dexamethasone

426
Q

What are the side effects of corticosteroids?

A

Adrenal suppression

Musculoskeletal effects

427
Q

give 2 muscloskeletal effects associated with corticosteroids?

A

muscle wasting and increased fracture risk

428
Q

give one gi side effect associated with corticosteroids?

A

GI bleeding

429
Q

give 2 mood changes that might occur with use of corticosteroids?

A

more energy or psychosis

430
Q

true or false: it is important to try and ensure that patients are on corticosteroids to treat GVHD for the
shortest term,high dose at start then rapidly taper over 1-2 months

A

true

431
Q

name one newer agent which may be used for refractory GVHD?

A

rituximab
..
infliximab
etanercept..

432
Q

Managing SEs of chemo…..

what drugs exert their effects on rapidly dividing cells: cancer and some helathy (bone marrow, GI mucosa, skin)..

A

cytotoxic
thus many SEs

433
Q

What side effect of chemotherapy would a HCP be most concerned about

A

myelosuppression

434
Q

Which 2 side effects of chemotherapy are patients most concerned about?

A

Nausea and vomiting

Hair loss

435
Q

bone marrow = organ most commonly affected by chemo and
myelosuppression = dose limiting tox for most chemo drugs, 2 exceptions

A

vincristine
bleomycin

436
Q

Why does neutropenia, thrombocytopenia and anaemia occur with chemotherapy?

A

Chemo kills immature cells so when mature cells die, there aren’t enough new cells to replace them.

happens wuick as EBC lower t1/2 than RBC, so will die off naturally

437
Q

predisposing factors to neutropenia and infection (most important haematological tox due to risk of life threatening infection)?

A
  • depth + duration of neutropenia
  • loss of cell-mediated and humoral immunity
  • mucosal damage
438
Q

What does a longer nadir duration mean?

A

Greater risk of developing serious infection.

439
Q

Why is G-CSF given before SCT?
management of neutropenia

A

to stimulate new stem cells

440
Q

How is neutropenia managed?

A

G-CSF

prophylactic antibiotics or anti-fungals

441
Q

if px presents with neutropenia and fever, need prompt treatment with what?

A

broad spec antibiotics

442
Q

what drugs may be given as prophylaxis for px going through chemo?

A

antibiotics

443
Q

3 effects of cytotoxic drugs on GI tract?

A

nausea and vomiting
oral mucositis
diarrhea

444
Q

How are nausea and vomiting categorised in 3?

A

Acute (first 24 hours)

Delayed (24 hours onwards)

Anticipatory

445
Q

nausea and vom management through which 2 drug classes?

A

5HT3 receptor antagonists
NK1 antagonists

446
Q

Give 2 examples of dopamine antagonist anti-emetics?

A

metoclopramide

domperidone

447
Q

Give an example of a 5-HT3 antagonist anti-emetic?

A

ondansetron

448
Q

Give an example of an antihistamine anti-emetic?

A

cyclizine

449
Q

Give an example of an NK1 antagonist anti-emetic?

A

aprepitant

450
Q

Give an example of anticholinergic anti-emetic?

A

hyoscine hydrobromide

451
Q

Give an example of a corticosteroid anti-emetic?

A

dexamethasone

452
Q

4 divisions of emetogenicity of chemo regimens?

A

high emetogenic risk
moderate
low
minimal

453
Q

4 divisions of emetogenicity of chemo regimens?

A

high emetogenic risk
moderate
low
minimal

454
Q

What chemotherapy regimens are highly emetogenic?

A

SCT schedules
cisplatin based

455
Q

What chemotherapy regimens are minimal emetogenic?

A

vincristine
bleomycin

456
Q

What risk factors make pts more prone to nausea and vomiting?

A

young age

female

previous motion/morning sickness

457
Q

metoclopramide + dexamethaone = example of what division of emetogenicity?

A

moderately

458
Q

symptoms of oral mucositis

A

pain

dry mouth

altered taste

ulceration

459
Q

how is oral mucositis treated?

A

mouthwashes
topical steroids
sucralfate
mucaine
lignocaine gel

sucking ice cubes: lower blood supply

460
Q

5FU
MTX
anthracyclines
cytarabine

are common culprits of what SE?

A

oral mucositis

461
Q

How is chemotherapy associated diarrhoea managed?

A

loperamide: may need to exceed usual max dose
codeine
octreotide if v severe

462
Q

what 2 drugs often -> diarrhea?

A

5FU
irinotecan

also occurs with majority of nibs

463
Q

main concern with conventional chemo: alopecia.
how is this prevented?

A

scalp cooling

464
Q

alopecia often seen with
T
A
E
B
I

A

taxanes
anthracyclines
etoposide
bleomycin
ifosfamide/ cyclophosphamide

465
Q

3 Symptoms of PPE/ hand-foot syndrome?

A

tenderness

tingling

peeling skin

466
Q

how is PPE managed?

A

dose interruption and reduction
chiropody
cushion based footwear

467
Q

How is tumor lysis syndrome prevented with allopurinol?

A

Allopurinol prevents the formation of uric acid
but no effect on existing urate

468
Q

Why might (rasburicase) recombinant urate oxidase be given in tumour lysis syndrome?

A

breaks down uric acid that has already been made.

Humans do not naturally produce urate oxidase so a recombinant form is used in practice

  • high risk px: high presenting WCC, v bulky, chemo sensitive disease
469
Q

What class of cancer drugs can cause temporary infertility in men?

A

Alkylating agents

470
Q

What service is offered to men who undergo chemotherpy prior to it?

A

Sperm banking

471
Q

What are the two main effects chemotherapy has on ovaries?

A

amenorrhoea

menopausal symptoms

472
Q

What strategies are used to maintain fertility in women receiving chemotherapy treatment?

A

IVF

egg freezing

ovarian tissue freezing

473
Q

Pulmonary toxicity is most commonly seen with what cancer therapy drug?

A

bleomycin

474
Q

Nephrotoxicity is most commonly seen with what cancer therapy drugs?

A

Cisplatin

Ifosfamide

Methotrexate

475
Q

pukmonary tox is more likely with IV bolus or long infusion?

A

IV bolus

476
Q

busullfuran, MTX, carmustine are 3 other drugs that can damage what?

A

lungs

477
Q

nephrotox can cause renal tox and …

A

electrolyte disturbances

478
Q

for high dose MTX alkalinise urine to prevent what?

A

drug precipitating in renal tubules

479
Q

Neurotoxicity is most commonly seen with what cancer therapy drugs?

A

Cisplatin

Oxaliplatin

Vinca alkaloids

Thalidomide

480
Q

neurotox may cause what 2 types of neuropathy?

A

peripheral: pins and needles

autonomic: constipation

481
Q

Which vinca alkaloid is most likely to cause neurotoxicity?

A

Vincristine

482
Q

neurotox likely associated with high doses and long term usage so doses capped at what?

A

2mg

483
Q

Cardiotoxicity is most commonly seen with what cancer therapy drugs?

A

antharacyclines

484
Q

cardiotox main concern is HF, related to what?

A

cumulative tox

485
Q

dexrazoxane (free radical scavenger) is used to try and prevent cardiotox via long infusions or alt drugs such as

A

mitoxantrone

486
Q

side effects of novel therapies?

A

infusional tox with mabs
rash with EGFR
HTN with VEGF targets
immun e related w CPI

487
Q

What do the side effects of checkpoint inhibitors usually affect?

How long do they take to appear?

A

Skin

GI tract

weeks to months

Health 32 (11 decks)

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