Cancer (treatment) Flashcards
(488 cards)
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
2
Q
3 types of cytotoxic chemo?
A
alkylating agents and nitrosureas
antimetabolites
natural products
3
Q
ifosfamide, cyclophosphamide, melphalan, chlorambucil, cisplatin, carmustine
are all examples of what type of chemo drugs?
A
alkylating agents and nitrosureas
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
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)
6
Q
why can alkylating agents + nitrosureas act at any point of cell cycle?
A
as targeting DNA directly
7
Q
what are the 2 main side effects of alkylating agents and nitrosureas?
A
teratogenic and carcinogenic
8
Q
most alkylating agents are bi or monofunctional?
A
bifunctional (2 alkylation products)
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
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
11
Q
whats mechlorethamine used to treat?
A
hodkins lymphoma
12
Q
Why are nitrogen mustards rarely used for cancer therapy? 3 SE
A
myelosuppressive
corrosive
toxic
13
Q
What is melphalan (hows it diff to mechlorethamine)?
A
2x Cl groups on end instead of CH3.
14
Q
How is melphalan administered and why?
A
IV and oral as stable
as preconditioning pre-transplant
15
Q
What is melphalan used to treat?
A
Multiple myeloma
cancer of plasma cells: mature B cell that produces antibodies
16
Q
What is the risk with prolonged use of melphalan?
A
myelodysplasia
17
Q
What is cyclophosphamide? type of drug, MoA
A
alkylating agent produg that is converted to its active form in the liver.
18
Q
the 2 cytotoxic metabolites of cyclophosphamide?
A
- aldophosphamide
- phosphamide mustard (+ acrolien)
(carboxyphosphamide)
18
Q
with cyclophosphamide, px at risk of haemmorhagic cystitis (bladder inflamm and bleeding) why?
A
acrolein a bladder irritant is produced as metabolite
19
Q
What is bendamustine used to treat?
A
chronic lymphocytic lymphoma
Non-hodgkin’s lymphoma
(CLL, indolent NHL) better tolerated than R-CHOP
20
Q
Give 3 examples of metal salts
A
Cisplatin
Carboplatin
Oxaliplatin
21
Q
How do metal salts work?
A
They inhibit DNA synthesis, through the formation of intra- and inter- strand cross links.
22
Q
cisplatin has severe SEs, name 3
A
nephrotox
neurotox
ototox
23
Q
What do metal salts bind to in DNA?
A
guanine groups
24
cisplatin t1/2 short or long?
long terminal t1/2 of 60h
25
How do antimetabolites work?
Works by inhibiting DNA synthesis and protein synthesis.
26
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?
inhibition of critical enz in nucleic acid synth
or
incorporated into nucleic acid -> incorrrect codes, cell death
27
what is the antidote for acrolein? and how?
MESNA
mops up the acrolein
28
What phase in the cell cycle do antimetabolites target?
S phase
as both mechanisms -> inhibition of DNA synth + cell death
29
examples of anti-metabolites?
folate antagonists
pyrimidine analogues
purine analogues
ribonucleotide reductase inhibitors
30
MOA of 5-FU drug?
= pyrimidine analogue that can be misincorporated into RNA and DNA in place of uracil or thymine
31
what enzyme does 5FU inhibit?
activated in vivo + inhib
thymidylate synthase (important for pyrimidine synth. dUMP -> dTMP)
32
what enzyme does MTX inhibit?
DHFR
important in folate cycle: DHF -> THF
33
What happens to folate in normal cells?
Reduced to dihydrofolate and then tetrahydrofolate needed for thymidine and purine synthesis.
34
How do folate antagonists work?
Competitively inhibit DHFR and therefore inhibit thymidine and purine (nucleotide) synthesis.
35
Mechanism of action for methotrexate? simple
Inhibits dihydrofolate reductase, leading to the inhibition of DNA and RNA synthesis.
36
name 3 examples of folate antagonists?
MTX
pemetrexed
raltitrexed
37
MTX affinity for DHFR enz is 100,000x that of what?
folic acid
38
How can the block caused by methotrexate be overcome?
Folinic acid
(form of THF, bypasses the block. given w MTX in practise as rescue for healthy cells)
39
What is the consequence of the production of excess dihydrofolate reductase?
How can it be overcome?
methotrexate resistance
increase the dose (escalation, seen in practise)
40
4 Clinical indications of methotrexate in cancer
osteosarcoma
breast cancer
lymphoma
acute lymphoblastic leukaemia ALL
41
What toxicities can MTX use cause? 3 MTX SEs
Myelosuppression
Mucositis
Renal
42
how is MTX cleared?
renally (up to 80% unchanged in urine)
so urine pH checked by nurses before admin.
43
when is folic acid prescribed w MTX?
alternate days to MTX dose
one per day or once a week
44
esp w higher doses of MTX, why do we need alkalisation of urine (pH>7) and vigorous hydration?
in neutral/ acidic env, MTX will crystallise out in renal tubules can -> kidney damage :(
45
what the terminal t1/2 of MTX?
8-10h but may inc to 24-36h if 3rd space accumulation (pleural/peritoneal effusion) :(
46
What drug interactions must be considered when prescribing MTX?
aspirin/ciprofloxacin/NSAIDs reduce tubular secretion of MTX, can inc MTX levels and tox
47
what is leucovorin/folinic acid? and role?
form of THF
maintain normal cell functions - reverses MTX toxicity
48
Why is folinic acid given to patients?
so healthy cells have enough folate to maintain normal cell functions.
reverses mucositis and myelosuppression
49
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?
lower levels of RFC- reduced folate carrier, needed for cell uptake
- lower conc will accumulate in cancer cells v healthy tissue
50
why do you need less folinic acid to neutralise MTX in cancer cells (vs healthy)?
cancer cells have less RFC = less effective at taking up folinic acid so need less
51
if giving rescue treatment (leucovorin/folinic acid) after chemo, wont it rescue cancer cells too?
no bc of differentials in uptake of folinic acid ! (RFC)
52
What are pyramidine analogues?
"fradualent" nucleotides
cytosine, thymine, uracil
-> mimic thus interfere w DNA synth
53
3 examples of pyrimidine analogues?
5-fluorouracil (5-FU),
gemcitabine,
capecitabine - erratic oral absorption
54
what is the prodrug of 5FU?
capecitabine
55
how does 5-FU work?
(pyrimidine analogue)
Activated to 5-F-dUMP, which inhibits thymidylate synthase!
56
How can the activity of 5-FU be enhanced?
Co-administer folinic acid to stabilise the complex
57
What is 2nd activated form of 5-FU and what does it do?
5-FUTP which inhibits RNA synthesis
58
How is 5-FU given?
prolonged IV infusions due to short half life (15mins)
also as its working in S phase
59
what PK parameter of 5FU led to interest in oral analogues eg capecitabine?
(IV preferred)
v erratic oral absorption (3-90%)
60
What were the 5 principal uses of 5-FU?
colorectal
breast
stomach
oesophagus
head and neck
(anything GIT)
61
for phase specific drugs, what type of infusions more beneficial?
LONG infusions as it maximises exposure.
if alkylating agents (target cells @ any point in cell cycle) doesnt matter how u give it
62
What is capecitabine?
oral prodrug of 5-FU
undergoes enz conversions to 5-FU in liver and tumour cells
63
clinical uses of capecitabine?
CRC
breast
gastric
pancreatic cancer
biliary
64
What toxicity can capecitabine cause?
Palmar Plantar Erythema PPE
65
is capecitabine or 5-FU better?
capecitabine better tolerated
but experience more hand and foot syndrome: SE
66
How is capecitabine activated? ()
3 step enzymatic conversion to 5-FU.
First 2 steps in liver
Last step in tumor by enzyme thymidine phosphorylase !!
67
Apart from capecitabine, name two other pyrimidine analogues
Gemcitabine
Cytarabine
68
gemcitabine is converted to gemcitabine triphosphate which in incorporated into DNA in place of deoxycytidine triphosphate.
how often given and for what cause?
weekly
pancreatic, NSCLC, bladder, breast cancer
69
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?
Most useful in tumours with high growth fraction, and mainly used for AML, ALL and certain lymphomas.
70
2 examples of purine analogues?
6-mercaptopurine
fludarabine
71
purine analogues can be incorporated into growing DNA chain in place of what?
natural nucleotides: A, G
72
what does 6 mercaptopurine do?
It blocks de novo purine synthesis
(inhibits various metabolic reactions including purine biosynthesis)
73
6-mercaptopurine is given orally as maintenance therapy for what cancer?
ALL
74
How is 6-mercaptopurine metabolized?
What caution must be considered?
Metabolised to its inactive form in liver by xanthine oxidase.
Caution with allopurinol
75
What is a prodrug of 6-mercaptopurine
Azathioprine
76
what is fludarabine?
active triphosphate, 2F-ara-ATP
inhibits variety of enzymes involved in DNA synthesis
ORAL
77
what is an example of ribonucleotide reductase inhibitor?
hydroxycarbamide
78
What does do hydroxycarbamide do?
Inhibits ribonucleotide reductase
Prevents manufacture of the purines and pyrimidines -> decrease in cellular levels of DNA
79
ribonucleotide reductase = enzyme essential for what?
generation of deoxyribonucelotides
80
hydroxycarbamide may also have what A. effects on DNA?
damage DNA directly, and inhibit DNA repair
81
What is hydroxycarbamide used to treat?
Haematological malignancies
- CML, polycythaemia, thrombocythaemia
oral 500mg capsules- dose tailored to response
82
antimetabolites work best in S phase why?
where high cell turnover - GI, haematological cancers
83
main 2 types of tox with antimetabolites?
GI and bone marrow
84
What are the two main drug classes in mitotic inhibitors?
Vinca alkaloids
Taxanes
85
How do mitotic inhibitors work?
Act on microtubules in the cell nucleus and by arresting metaphase, can inhibit mitosis.
M phase specifically
86
Microtubules are hollow rod like structures made of what?
protein tubulin, and they maintain a cells shape.
major part of mitotic spindle thus essential for distributing genetic material in cell division
87
MICROTUBULE is in dynamic eqm with intracellular pool of TUBULIN.
what drugs inhibit breakdown of microtubules -> tubulin?
taxanes
88
what drugs prevent assembly of microtubules from tubulin
vinca alkaloids
89
Give 2 examples of a vinca alkaloid
Vincristine
Vinblastine
90
How do vinca alkaloids work?
Bind to tubulin and prevent microtubule assembly
91
What dose is vincristine capped at? and why?
2mg regardless of weight due to neurotoxic effects
92
what is vincristine used in?
haematology and sarcoma and neuroblastoma
93
Where is vincristine metabolised? and why to be cautious?
liver - caution in liver impairment and w drugs metab via cyp450 system
.. and 70% elim in faeces
94
How is vincristine administered and why?
highly vesicant but IV infusion due to risk of intrathecal admin !!!
95
main toxicity w vincristine? and what is it caused by?
neurotox (typically cumulative) fatal if admin intrathecal!
96
What is brentuximan vedotin?
novel conjugate of anti-CD30 mab and MMAE (vincristine)
97
role of MMAE? context of brentuximab vedotin
inhibits polymerisation of tubulin
98
Taxanes are poorly water soluble and is formulated with cremaphor oil - what is the risk associated with this?
hypersensitivity reactions
(need pre medication)
99
What cancers are taxanes licensed for?
ovarian and advanced breast cancer
100
What main tox is associated with the use of taxanes?
Neutropenia
may be less if given weekly rather than 3 weekly
(also neurotox, alopecia, cardiotox)
101
Examples of taxanes apart from paclitaxel
docetaxel
abraxane
cabazitaxel
102
what taxane req pre-med with dexamethasone to minimise risk of hypersensitivity reacs and fluid retention?
docetaxel
103
Why is abraxane less likely to cause hypersensitivity?
because it is albumin-bound
.. used in pancreatic cancer
104
what taxane used for metastatic hormone refractory prostate cancer post docetaxel?
cabazitaxel
105
what 2 cancers is trabectedin licensed for?
advanced soft tissue sarcoma
relapsed ovarian cancer
106
topoisomerases are nuclear enzymes that cause what effect to DNA?
DNA strand breaks and therefore allows it to unwind during cell division
107
difference between topoisomerase I and II?
Topoisomerase I - causes single nick in DNA
Topoisomerase II - cleaves both strands
108
What do topoisomerase inhibitors do to the enzyme-DNA complex?
stabilise it and prevent re-ligation causing irreversible DNA strand breaks
109
What stage in the cell cycle do topoisomerse inhibitors target?
late S or early G2
110
what can inhibit topoisomerase II?
etoposide
111
Why is etoposide usually given IV?
oral absorption is erratic and BA only approx 50%
112
etoposide indications?
SCLC, testicular tumours, lymphomas
gen reserved for palliative ie advanced lymphoma
113
as well as standard tox, whats the risk that may occur 2-3yrs after treatment with etoposide?
secondary AML
etoposide similar to alk agents but not -> cell death, just mutations
114
what are 2 examples of topoisomerase I inhibitors?
topotecan
irinotecan
115
what topoisomerase I inibitor is licensed for:
oral: ovarian + cervical canver
IV: SCLC
topotecan
116
what topoisomerase I inibitor is licensed for advanced colorectal carcinoma?
irinotecan
117
What risk is associated with Irinotecan use?
Acute cholinergic syndrome (diarrhea, cramping, emesis)
pre-med w atropine: anticholinergic. given to prevent it
118
major class of antitumour antibiotics?
anthracyclines
119
4 moas of anthracycliens?
inhibit topoisomerase II
DNA intercalation
free radical formation
alkylation
120
what drug class are:
- doxorubicin
- daunorubicin
- idarubicin
- epirubicin ?
anthracyclines
121
What causes cardiotoxicity/ heart failure with the use of anthracyclines?
main SE
the formation of free radicals
122
Why is mitoxantrone (anti-tumour antibiotic) safer to use than anthracyclines?
structurally related but
Does not produce free radicals so is less cardiotoxic
123
mitoxantrone indicated for use in what 3
AML
breast
prostate cancers
124
What is actinomycin D?
How does it work?
anti-tumour antibiotic
binds to DNA and inhibits DNA-dependent RNA synthesis. Also inhibits topoisomerase 2.
sarcomas
125
What is mitomycin C?
How does it work?
anti-tumour antibiotic
causes cross-links between complementary DNA strands, which inhibits replication
lung/ intravesically for bladder cancer
126
why can you only give mitomycin C every 4-6 weeks?
causes delayed myelosuppression
127
What is bleomycin?
How does it work?
anti-tumour antibiotic
causes DNA strand scission resulting in fragmentation of DNA
128
what antitumour antibiotic indicated for testicular cancer, hodkins, NHL and can be gievn pleurally?
bleomycin
but risk of cumulative pulmonary tox
129
What is gemtuzumab ozogamicin?
a novel immunoconjugate of an anti-tumour antibiotic and an anti CD33 antibody
130
How does gemtuzumab ozogamicin work?
Binds to cells expressing the CD33 antigen.
Internalization of the conjugate.
Release of the calicheamicin moiety by acid hydrolysis within lysosomes.
131
Cancer screening...
currently there are screening programmes in the uk for what 3 cancers?
breast, cervical and colorectal
132
cancer screening can be opportunistic or?
population based
133
what is meant by cancer screening?
testing healthy people for signs of disease
134
why is screening done?
find cancer at an early stage or prevent deveopment to save lives
135
are cancer screening programmes the same as the tests a person might have when doctors are making a diagnosis of cancer?
no
136
true or false; cancer screen tests are there to diagnose cancer?
false
137
what makes a cancer suitable for screening?
-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 **
138
give one example of a physical test that might be included in a cancer screen?
checking skin moles
139
give one example of a lab test that might be included in screens?
PSA measurement
prostate specific antigen
140
give one example of an immaging procedure that might be part of a screen?
breast mammography
141
give one example of a genetic test that might be part of a screen?
BRCA testing
if family hx of breast cnacer
142
give 4 components that can be included in screening tests?
physical exam, lab tests, imaging and genetic tests
143
usually we should screen people who are at increased risk of disease. list 4 factors that might put someone at an increased risk?
family history, genetic mutation, exposure to carcinogens, age
144
what is the most important driver that increases someones risk of disease?
advancing age
145
true or false: the risk benefit ratio of screening very elderly people may not be clinically worthwhile therefore must be assessed?
true
146
Advantages of cancer screening?
Better outcomes.
Less radical therapy needed.
Reassurance .
Savings because therapy is less complex.
147
Disadvantages of cancer screening?
Over-treatment of borderline abnormalities.
False reassurance for pts with false negative results.
Resource costs of screening systems.
148
what type of trial is ideal to assess a screening programme?
large RCT with long follow up
149
how long is sufficient to adequately assess a screening programme?
at least 10 years
150
what are 3 possible pitfalls from looking at registry data?
lead time bias, overdiagnosis, health screenee bias
151
what is meant by lead time bias?
screened patients appear to live longer because survival calculation includes time preceding when cancer would have been picked up clinically
152
what is understood by overdiagnosis in the context of skewing survival rates?
screening picks up cancers that would not have clinically manifested
153
what is understood by healthy screenee bias?
people attending screening may be more likely to display healthy lifestyle behaviours
154
What aged women are offered breast cancer screening in the UK? and how often?
50-70 every 3 years
155
high risk patients may be eligible for earlier breast cancer screening. What factors might render them high risk?
family history, previous chemotherapy for cancer
156
what x ray is used in breast cancer screens?
mammogram
157
true or false; breast cancer screens do not carry an increased risk of over diagnosis?
false
158
What aged women are offered cervical cancer screening in the UK? and how often?
25-64
every 3 years until 49 years then every 5 years
159
Why is cervical cancer screening not offered for women less than 25?
it is rare under this age
might lead to unecessary treatment, abormal cell changes often become normal
160
the incidence of cervical cancer in the UK is expected to decrease further due to the implenatation of what vaccination programme?
HPV
161
HPV causes the majority of cervical cancer cases with the majority being due to what 2 subtypes?
16 and 18
162
why are women above 65 not routinely offered cervical cancer screens?
unlikely to get it
163
what is the exception which means that women above 65 would be invited to a cervical cancer screen?
1 of last 3 tests was abnormal
164
the screening procedure for cervical cancer involves a small sample of cells being taken from the cervix. What is it first checked for?
HPV
if not found, no further tests taken
165
if certain types of HPV are found in a cervical cancer screen what are the next steps?
sample checked for any changes in cervix cells using liquid based cytology
166
if changes are identified in the cells of the cervix after using liquid based cytology, what procedure are patients invited for?
colposcopy
167
currently in england people between what age range are sent a home bowel cancer test kit every 2 years?
60-74
168
why is the faecal immunochemical test (FIT) to screen for bowel cancer instead of the faecal occult blood test (gFOBT) now?
more accurate and easier to use
169
true or false: NHSE are hoping to lower the bowel screening age to 50 in the future?
true
170
the FIT kit to screen for bowel cancer was introduced in 2019. What does it use to detect human blood in stool?
specific antibodies
171
for people with positive detection of human blood in stool after a FIT test, what will be they offered?
colonscopy
172
give 2 reasons that might explain the significant increase in the incidence of prostate cancer in the past 10 years?
ageing population and earlier detection using PSA screening
173
what improvement is required of the PSA test?
help distinguish between aggressive and indolent cancers
174
Why is prostate cancer not screened for yet? regularly
PSA test needs development.
Lack of quality trial data is available.
175
what may increase PSA levels (above 5) other than prostate cancer?
UTI
rigorous exercise before test
drug that interferes w PSA levels
176
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?
annual low dose CT scan
177
what is rhe role of the pharmacist in cancer screening?
encourage people to attend, provide information and reassurance about the process
178
name some barriers to cervical screening
women embarrassed about having smear test
worried about result
concerned about procedure and pain
dont think at risk
unaware of screening
179
Novel therapies for cancer...
biologic agents/ immuno therapies may be non-specific such as..
cytokines like interferon/ immunomodulators like thalidomide
180
biologic agents/ immuno therapies may be more targeted such as...
mabs: rituximab
181
When might a chronic myeloid leukaemia patient be given extra lymphocytes?
after an allogenic stem cell transplant, the patient may relapse and the pt can be given donor lymphocytes to prevent this.
182
IL2 and interferon a are both examples of what type of biologic?
cytokines
183
which cells produce il2?
activated t cells
184
what is the moa of il 2?
stimulates t cell proliferation and activates nk cells
185
what two types of cancer has il 2 been used in the treatment of?
renal cell and melanoma
186
interferon a have a number of immunomodulatory effects, give some of these?
activation of nk cells,
modulation of antibody production,
inducing antigen presentation on tumour cells
187
list some of the indications, of interferon a other than CML?
NHL, renal cell carcinoma and multiple myeloma
188
why are cytokines given as drug therapy?
substances alr part of IS, give in drug form to strengthen IS and have anticancer effect
(rarely used in practaise tho)
189
thalidomide is an immunomodulator and has a role in the treatment of what type of cancer?
multiple myeloma
190
Drug class of thalidomide?
immunomodulator
191
how does thalidomide work to help treat cancers such as multiple myeloma?
inhibits angiogenesis to prevent tumour spread
192
true or false: newer varients of thalidomide such as lenalidomide and pomalidomide are now being used in the clinic?
true
193
binding of mabs to tumour associated antigens can result in the destruction of tumour cells by what 2 processes?
complement activation or ADCC
194
pembrolizumab and nivolumab are active in many cancers. What do they block to release an immune system 'break'?
PD1 receptor
195
what is the rationale behind attaching antibodies such as mabs to cytotoxic radioisotopes, toxins or drugs?
targeting effect
196
pembrolizumb
nivolumab
atezolizumab
ipilumumab
abatacept
all examples of what class of drug?
checkpoint blockade
.. activating IS
197
pembrolizumb and nivolumab inhibit PD1 to treat what cancers..
melanoma
lung
bladder
..
198
what does atezolizumab inhibit and treat?
PD1
bladder and lung
199
what does ipilumumab inhibit and treat?
CTLA4
advanced melanoma
200
abatacept enhances ctla4, true or false?
true
201
give two uses for abatacept?
RA and kidney transplant rejection
202
where is the CTLA4 receptor found?
on T cells
203
effect of antibody binding to CTLA4?
(on T cells)
switches off T cell activation
204
2 ways to get negative regulation during effector phase?
use mab to block pd1 or pdl1
205
What mab is licensed for:
follicular lymphoma
high grade B cell lymphoma
CLL
rituximab/ mabthera
206
rituximab is a monoclonal antibody specific for X and expressed on the surface of mature b cells
CD20
207
cd20 is expressed on the surface of which mature cells?
B cells
208
give the 3 different ways by which rituximab binding causes cell death?
apoptosis induction,
px immune system activation
sensitisation of resistant lymphoma cells to conventional chemo
209
the most common side effects of rituximab are infusion related, give some examples?
fevers, chills and rigors
210
why is it important to premedicate prior to giving rituximab? rare SE
danger of cytokine release syndrome
211
what drugs can you use to premedicate with before giving rituximab? 3
antihistamine, paracetamol, steroids
212
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?
trastuzumab/ herceptin
213
What cancers is trastuzumab used for?
HER +ve breast cancers
214
trastuzumab can be used as monotherapy or in combination with paclitaxel or what other drug, to treat metastatic breast cancer?
docetaxel
215
what is the only uk licensed indication for alemtuzumab/ mabcampth?
MS
216
what relatively specific antigen for lymphocytes does alemtuzumab (MabCampath) target?
CD52
217
What is CAR T cell therapy?
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
(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?
CD19
219
what is there a very high risk of with kymriah, yescarta and tecartus use?
CAR T therapy
cytokine release syndrome CRS
(+ neurological complications)
220
what is the name given to hollow cylindrical structures made from a number of different proteins?
proteosomes
221
2 locations where proteosomes are found?
nucleus and cytoplasm
222
proteosomes play a key role in the cell and degrade a number of protein substrates. Why is this important?
accumulation of proteins is toxic to the cell
223
proteosome inhibitors have become standard treatment for what type of cancer?
multiple myeloma
224
what is the drug class of bortezomib?
proteosome inhibitor
225
what is the first line drug used to treat multiple myeloma?
bortezomib
226
give 3 side effects that are associated with bortezomib?
neuropathy, thrombocytopenia and fatigue
227
bortezomib is only licensed for IV bolus admin, true or false?
false
SC better, easier and lower risk of neuropaty
228
carfilzomib is a newer proteosome inhibitor and is given as an IV infusion, but is associated with what type of toxicity?
cardiac
229
can ixazomib be given orally, yes or no?
yes
230
true or false: ixazomib is NICE approved as part of an all oral combination with lenalidomide and dexamethasone?
true
231
what class of drugs are known as nibs?
protein kinase inhibitors
232
what do nibs target that is different from traditional chemo agents?
growth factors and their receptors on individual cancer cells
(instead of DNA -> cell damage)
233
how do nibs differ in their toxicity profiles to traditional chemo agents?
less nausea and myelosuppression
234
give a drug class that can be used as a targeted therapy whereby, individual targets mean that there are individual toxicities?
protein kinase inhibitors nibs
235
CML is characterised by the 9;22 translocation, what is this chromosome known as?
philadelphia
236
the philadephia chromsome on chromosome 22 results in the production of a new fusion gene known as?
BCR-ABL
237
what is rhe product of the BCR-ABL fusion gene and why is this a problem?
bcr-abl tyrosine kinase which is leukaemogenic
238
name one drug which is used in CML and is a selective inhibitor of bcr-abl kinase?
imatinib
239
Mechanism of action of imatinib in chronic myeloid leukaemia
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
Common toxicities associated with imatinib
haematological, diarrhoea, rash, oedema, nausea, cramps, headache
241
Imatinib is metabolised by CYP3A4 and therefore has many DDIs with what drug type?
enzyme inducers
242
name some enzyme inducers that would have DDI with imatinib (cyp3a4 metabolism)
itraconazole, clarithrimycin, phenytoin, rifampicin, warfarin, ciclosporin
243
give one mutation which occurs commonly in AML?
FLT3
244
how do FLT3 mutations benefit cancer cells?
constitutive kinase activation,
promotes growth, survival and anti apoptotic signalling
245
Give an example of a first gen FLT-3 inhibitor - protein kinase inhibitor
Midostaurin
246
is midostaurin a first or second generation FLT3 inhibitor?
furst
247
what are 3 PARPi that are currently licensed for use in the UK in some capacity to treat ovarian cancer?
olaparib, niraparib and rucaparib
248
what are parp enzymes important for?
DNA repair
249
what are olaparib and talazoparib licensed for?
breast cancer
250
generally PARPi require the prescence of what mutation to exert their action?
BRCA
251
What is the role of BCL-2?
anti-apoptotic factor
inhibits Bax/Bak
252
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?
CLL
253
cell damage leads to the release of pro apoptotic proteins such as BAX, BID and BAK. How do these proteins lead to apoptosis?
promote release of cytochrome c from mitochondria, triggers release of caspase enzymes, drives apoptosis
254
What protein inhibits the following pro apoptotic factors:
BAX, BID, BAK?
BCL-2
255
what is the only currently licensed BCL-2 inhibitor?
venetoclax
256
what two cancers is the treatment of venetoclax approved for?
CLL, AML
257
why is important that venetoclax is started at a low dose and slowly titrated upwards?
high risk of tumour lysis syndrome TLS
258
why is venetoclax given with posconazole in AML patients?
beneficial DDI
very expensive, posconazole increases exposure so a lower dose can be used
259
VEGF is a key growth factor that promotes what process?
angiogenesis
260
why might we want to inhibit angiogenesis of cancer cells in cancer patients by VEGF?
can halt tumour growth and spread
261
name a modified antibody that can be used to target/inhibit VEGF in order to stop angiogenesis?
afilbercept
262
name a mab that can be used to target VEGF in order to prevent angiogenesis?
bevacizumab, ramucirumab
263
name a TKI that can be used to target VGEF and inhibit it in order to stop angiogeneis (commonly in kidney cancer)?
sunitinib , axitinib
264
3 types of drugs that can target VEGF? inhibiting angiogenesis
MABs
TKIs
modified antibody
265
What is CPX-351?
How does it improve "old" chemo drugs?
lipososmal delivery system
enhances uptake
longer half life
266
cpx-351 is a liposomal delivery system that contains what 2 drugs?
cytarabine and daunorubicin 5:1 molar ratio
267
why might it be more beneficial to use CPX-351 liposomal formulations to enhance older chemo agents?
enhanced marrow conc and improved uptake into AML blasts
268
Drug treatment: clinical and economic.....
Describe the absorption characteristics of most anticancer drugs.
poor oral absorption
unstable in gastric acid
269
name one 5FU derivative drug that is given orally?
capecitabine
270
what advice would you give to patients taking etoposide or uftoral capsules with regards to food?
take before food
271
what advice would you give to patients in relation capecitabine and food?
with or after food
prodrug of 5FU
272
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?
small lipophilic drugs have to be able to cross bbb
273
how are most anticancer drugs metabolised? and where?
cytochrome P450 in liver
274
examples of small lipophilic drugs used in CNS disease?
MTX!!
cytarabine
BCNU
can cross BBB
275
wherever possible what bw should be used to dose obese patients to ensure that toxicity does not occur?
actual bw
276
why might px with liver disease be at risk of increased tox of anti cancer drugs?
commonly metabolised by p450 enzymes in liver
277
active drug or metabolites are usually excreted by what organ?
kidneys
278
name 3 drugs/ drug classes that can interefere with renal excretion of cytotoxic drugs?
mtx, penicillins, nsaids
279
What key cancer drugs need dose reductions in renal impairment?
cisplatin
methotrexate
.. carboplatin, bleomycin
280
What key cancer drugs can be nephrotoxic?
cisplatin
methotrexate
mitomycin C
281
cisplatin is a nephrotoxic drug, what is it important that is adequate in patients?
hydration
282
name 2 drugs where adequate hydration in patients is essential?
cisplatin and ifosamide
283
what should be done to a patients urine if they are using high doses of mtx?
alkalinse
284
true or false: mitocycin c is a nephrotoxic drug and is associated with haemolytic uremic syndrome?
true
285
What key cancer drugs need dose reductions in HEPATIC impairment?
doxorubicin
vincristine
paclitaxel
286
What 4 key cancer drugs can be hepatotoxic?
nitrosoureas
methotrexate
cytarabine
6-mercaptopurine
287
mtx is hepatoxic, list 2 things that might occur to the liver due to use?
fibrosis and cirrhosis
288
why would you see elevated liver enzymes in nitrosoureas and cytarabine?
hepatotoxic
289
true or false 6MP is associated with cholestasis and necrosis due to its hepatic toxicity?
true
290
what 3 groups can the factors that determine the success of chemotherapy be divided into?
objective of treatment,
px factors,
factors related to tumour
291
what type of treatment objective: curing disease or focusing on symptom palliation as adjuvant to surgery, is likely to have aggressive chemo involved?
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
list 3 patient factors?
general medical condition, age, motivation
293
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?
0
294
would patients with PS scores of 3-4 be given chemo?
no
295
give one reason why children and young adults might tend to respond better to chemo compared to elderly patients?
link to decreased organ function (kidneys, bone marrow...) in elderly
296
give 2 things that can determine compliance in patients?
psychological status and motivation for treatment
297
list some factors that are related to the tumour that might influence whether chemo is given to patients or not?
sensitivity to chemo,
clinical stage and size,
growth characteristics
298
do less differentiated cells tend to be more or less aggressive?
more
299
do less differnetiated cells tend to be more or less sensitive to chemotherapy?
more
300
true or false: with each new cancer treatment introduced to a patient benefit and chances of success decrease?
true
301
is adjuvant chemo for some cancers like breast given before or after surgery or radiotherapy?
after
302
What cancers are often curative?
ALL and AML (especially in children)
NHL
303
What cancers are more than 30% responsive?
breast cancer
small cell lung cancer
multiple myeloma
CLL
304
What cancers are usually highly resistant?
non-small cell lung cancer
renal cell carcinoma
pancreatic cancer
305
What is the aim of adjuvant chemotherapy?
eradicate micrometastases
(diagnosis of primary cancer but also have other deposits elsewhere, too small to be picked up on scan)
306
why might tumour cell kinetics favour an adjuvant chemo approach to eradicate micrometasteses?
higher growth fraction and shorter cell cycle times when tumour burden is low
307
why should the regimen of adjuvant chemo ideally have low tox ?
proportion of patients will be cured already
308
is neoadjuvant chemo given before or after surgery is performed?
before
309
what is the principle that neoadjuvant chemo is based on?
px likely to have undetectable micrometastatic disease at presentation
310
What is neo-adjuvant chemotherapy?
Chemo given before surgery to shrink tumour.
311
what are the 3 potential advantages of neo adjuvant therapy?
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
what might be the disadvantage of giving neoadjuvant chemo?
increased infection risk if become unwell before chemo,
if chemo doesnt work tumour may grow and make surgery harder or impossible
313
why might combination chemo be more successful than a single chemo agent? 3 reasons
prevent resistant clones, cytotoxicity to resting and dividing cells, biochemical enhancement of effect
314
true or false: combination chemo should choose individually active drugs?
true
315
TRUE OR FALSE: for combination chemo drugs with overlapping toxicities should be chosen?
false
316
true or false: for combination chemo agents with different modes should be chosen?
true
317
true or false: for combination chemo, drugs should be used at their optimal dose and schedule?
true
318
for combination chemo, agents should be chosen that do/do not display cross resistance?
do not
esp w P glycoprotein pump- particular issue w natural products
319
why should the treatment free interval be the shortest possible for patients who are on combination chemo regimens?
allow recovery of most sensitive host tissue
320
cell cycle phases?
M
G1
S
G2
321
cytarabine, 5fu and mtx are all phase specific and work in what phase of the cell cycle?
S
322
what phase of the cell cycle does bleomycin work in?
G2
323
what phase of the cell cycle does etoposide work in?
G2
324
what phase of the cell cycle do vinca alkaloids work in?
M
325
what phase of the cell cycle does paclitaxel work in?
M
326
give an example (cytarabine) of how phase specifism leads to implications for scheduling?
cytarabine in AML given 12 hrly 8-10 days
327
name 2 antibiotics that are cell cycle specific?
doxorubicin, epirubicin
328
name 3 alkylating agents that are cell cycle specific drugs?
chlorambucil, cyclophosphamide, cisplatin
329
2 types of cell cycle nonspecific drugs
nitrogen mustard
nitrosureas: carmusting, lomustine
330
true or false, cytotoxic antibiotics and alkylating agents work at any point in the cell cycle?
true
331
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?
act on cells in and out of cycle so target resting and dividing cells
332
BEP is a combination regimen for testicular cancer is made up of what 3 drugs?
bleomycin, etoposide and cisplatin
333
what is the moa of bleomycin?
inhibits dna synthesis and arrests cell in G2
334
does bleomycin induce or lack myelosuppression?
lack
335
give 2 sites that belomycin is toxic to?
skin and mucous membranes
336
which toxicity is most associated with bleomycin:
pulmonary, cardiovascular, renal, hepatic
pulmonary
337
what is the drug class for etoposide and what does this mean ?
topoisomerase 2 inhibitor important for unwinding dna
338
etoposide is myelosuppressive and can present in patients as?
alopecia
339
is etoposide or bleomycin associated with moderate nausea and vomiting?
etoposide
340
why is etoposide given slowly/ what is trying to avoided?
hypotension
341
cisplatin is an alkyalting agent, what does this mean it does to DNA?
cross links
342
which of the following is associated with cisplatin
nephrotox
hepatotox
ototox
neuropathy
cns tox
pulmonary tox
nephrotox, ototox, neuropathy
343
is etoposide or cisplatin associated with severe nausea and vomiting?
cisplatin
344
which of the following myeloma drugs is associated with neutropenia
thalidomide
bortezomib
lenalidomide
pomalidomide
lenalidomide and pomalidomide
345
which of the following drugs is associated with thrombocytopenia
thalidomide
bortezomib
lenalidomide
pomalidomide
all except thalidomide
346
which of the following drugs is associated with neuropathy?
thalidomide
bortezomib
lenalidomide
pomalidomide
thalidomide and bortezomib
(not L and P)
347
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
thalidomide
348
from the following list of drugs diarrhoea is only associated with which drug ?
thalidomide
bortezomib
lenalidomide
pomalidomide
bortezomib
349
somnolence is associated with drug from the following list?
thalidomide
bortezomib
lenalidomide
pomalidomide
thalidomide
350
which of the following drugs is not associated with thrombotic risk ?
thalidomide
bortezomib
lenalidomide
pomalidomide
bortezomib
351
Stem cell transplantation...
the first line treatment for this condition is treatment with ABVD, what is the condition?
hodgkins
352
what drugs are part of the ABVD regimen for hodgkins?
adriamycin, bleomycin, vinblastine and dacarbazine
353
hodgkins patients are given ABVD every 2 weeks for how many months?
4-6
354
if patients relapse or there is no, or partial response to ABVD, what is the second line treatment for hodgkins?
different regimens such as IVE and ESHAP
355
What is the 3rd line treatment for hodgkins for both patients who are in remission and those who have had partial or no response?
autologous SCT
356
name 2 drugs that would be appropriate for 3rd or 4th line treatment for patients with hodgkins who have relapsed after autologous SCT?
brentuximab and nivolumab
357
if a patient is fit enough after 3rd or 4th line treatment for hodgkins, what might be offered?
allogeneic SCT
358
is autologous or allogeneic SCT associated with higher risks?
allogeneic
as stem cells are from a donor
359
for autologous SCT haematopoetic SC are harvested from the patient and stored. Under general anasthetic, where might the SC be removed from?
bone marrow or peripheral blood
360
process of an autologous SCT?
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
in order for peripheral SC harvest what endogenous hormone are patients given?
G-CSF
362
G-CSF injections are given 3-4 days prior to peripheral SC harvest for autologous SCT. What is the rationale behind doing this?
drives proliferation of wbc, stimulates stem cells to leave bone marrow and enter peripheral circulation
363
How might SC be removed from a patients peripheral blood for autologous SCT?
px hooked to apheresis machine, blood drawn out, enters machine, SC removed, blood returned to the patient
364
after stem cell harvest a high dose of chemo is given to patients. What cancer is BEAM or LEAM used for?
lymphoma
365
after stem cell harvest a high dose of chemo is given to patients. What cancer is melphelan used for?
myeloma
366
why do most chemotherapy regimens have a ceiling dose?
myelosuppression puts the patient at risk of infection as wbc, platelets and rbc are destroyed
367
after high dose chemo in the context of autologous SCT, patients are given rescue therapy. What is this?
reinfusing stem cells after chemo
368
what is the rationale behind rescue therapy?
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
what is the main difference between autologous and allogeneic SCT?
source of allogeneic SCT cells is donor
370
there are different types of allogeneic SCT due to variability in terms of what 3 things?
SC source, donor and intensity
371
list some different sources for SC for allogeneic SCT?
pb, bone marrow and umbilical cord
372
name some different donors that would be suitable for allogeneic SCT?
sibling, stranger, parent, child
373
full intensity is the strongest chemo that can be managed in the context of allogeneic SCT, patients above what age might recieve reduced intensity?
45
374
what is the likelihood of a sibling being a suitable donor match for allogeneic SCT?
25% (punnett square)
375
why is rejection rare to see in cases of autologous SCT?
immune system destroyed and not functioning therefore unable to reject transplant
WBCs wiped out
376
What are the main complications of allogeneic SCT?
Graft vs Host disease
Infection
377
what is GVHD?
new immune rejects patient and attacks host
378
GVHD can be classed as acute or chronic, what is the difference between the two?
acute is 0-100 days and chronic is beyond 100 days
379
3 areas that are commonly affected by GVHD?
skin, gut and liver
380
true or false, GVHD affecting the liver is usually only picked up on blood tests, before there is a presenatation of jaundice?
true
381
what family of cells drives GVHD?
T cells
382
What is cytomegalovirus?
herpes virus that majority of theUK are seropositive for
383
Why is allogenic SCT better than autologous SCT?
no risk of infusing malignant cells eg myeloma
immune mediated effects....
384
whats the main cause of death in px not cured by allograft?
infection
GVHD
over prolonged period... relapse!!
385
what can DLI donor lymphocyte infusions induce in px who relapse after an allograft?
remissions
386
T/F
px who develop mild GVHD hane better outcome than px who dont develop it?
true
387
are high or low ciclosporin levels associated with improved survival rates?
low
388
What is the GVL effect?
graft vs leukemia
The new immune system after a SCT can attack and kill any residual cancer cells remaining after the transplant.
389
What immunosuppressants are given to prevent GVHD?
suppress T cells
Ciclosporin/ tacrolimus
Methotrexate
Alemtuzumab
Mycophenolate
ATG
390
What drugs are given to treat GVHD?
Corticosteroids
391
ciclosporin is the mainstay of CVHD prophylaxis and is used in combination of low doses of what other drug?
MTX
392
true or false: ciclosporin is widely used in both solid organ and SC transplants?
true
393
how does ciclosporin work to prevent GVHD?
suppresses t cell activation via inhibition of calcineurin
(enz important in T cell activation)
394
is ciclosporin usually start the day before or the day after SCT?
before -1
395
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?
slow infusion
396
at what point what you switch iv ciclosporin to oral?
once mucositis resolves
397
nephrotox is associated with ciclosporin and may be made worse if used what other nephrotoxic drugs?
amphotericin, vancomycin and gentamicin
398
Side effects of ciclosporin
nephrotoxicity
hypertension
hypomagnesaemia
hepatotoxicity
neurological syndromes
hirsutism
399
ciclosporin may cause htn. name a drug, dose and its class that can be given to treat this?
CCB, amlodipine, 5-10mg
400
hypomagnesaemia is very common with ciclosporin use. what 2 things can be given to patients to treat this?
mg aspartate sachets or mg citrate tablets
401
ciclosporin is associated with neurological syndromes, give one way that this might manifest in patients?
fits
402
what symptoms are common in patients with ciclosporin but if severe can suggest high levels?
anorexia, nausea, vomiting, tremor
403
give 2 symptoms that are associated with prolonged use of ciclosporin?
hirsutism and gum hypertrophy
404
How is ciclosporin metabolised?
by CYP450 in the liver
405
enzyme inhibitors such as
azoles
clarithromycin
grapefruit juice
will increase/decrease levels of ciclosporin
increase
406
enzyme inhibitors such as
phenytoin,
rifampicin,
carbamazepine,
st johs wort
will increase/decrease levels of ciclosporin
decrease
407
what enzyme does tacrolimus inhibit to exert its moa?
calcineurin
408
true or false: tacrolimus and ciclosporin levels are monitored in patients?
true
409
T/F tacrolimus is interchangeable with ciclosporin?
true
works in same way
410
mtx is a conventional chemo agent but used in high or low doses to prevent GVHD?
low
411
gave one adverse effect that is commonly associated with mtx use?
mucositis
412
what is the rationale of giving 3 doses of folinic acid 15mg, starting 12 hrs after mtx?
reduce the risk of mucositis SE
413
what 2 actions would be recommended to patients on mtx for GVHD prevention who develop mucositis?
consider omitting day 12 dose if severe
or prescribe folinic acid mouthwash
414
what is the moa of mycophenolate?
inhibits dna production in lymphocytes
415
true or false: mycophenolate is commonly used in solid organ transplantation?
true
416
give 3 side effects associated with mycophenolate use?
GI, increased risk of infection, reduced blood count
417
what is alemtuzumab used for in the context of allogeneic SCT?
prophylaxis and treatment of GVHD in steroid refractory periods
418
alemtuzumab is a monoclonal antibody against CD?
CD52
419
pre medication is required for alemtuzumab and is given slowly over 4 hrs. Why might this be the case?
risk of infusion related reactions
420
alemtuzumab dose: 10mg daily from day -5 to -1
or 30mg od from -2 and -1.
why is it given before transplant as well?
long t1/2
will hang around for few weeks
421
true or false: alemtuzumab has an increased risk of bacterial, viral and fungal infections
true
422
ATG/ALG is anti lymphocyte immunoglobulin and is used to prevent GVHD, What does it do to the number of circulating lymphocytes?
reduces
423
true or false: ATG/ALG is derived from rabbits that have been injected with human lymphocytes?
true
424
there is also an equine form of ATG/ALG used tot reat what?
aplastic anaemia
425
corticosteroids are the first line treatment in GVHD, name 3 suitable agents?
prednisolone, methylprednisolone, dexamethasone
426
What are the side effects of corticosteroids?
Adrenal suppression
Musculoskeletal effects
427
give 2 muscloskeletal effects associated with corticosteroids?
muscle wasting and increased fracture risk
428
give one gi side effect associated with corticosteroids?
GI bleeding
429
give 2 mood changes that might occur with use of corticosteroids?
more energy or psychosis
430
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
true
431
name one newer agent which may be used for refractory GVHD?
rituximab
..
infliximab
etanercept..
432
Managing SEs of chemo.....
what drugs exert their effects on rapidly dividing cells: cancer and some helathy (bone marrow, GI mucosa, skin)..
cytotoxic
thus many SEs
433
What side effect of chemotherapy would a HCP be most concerned about
myelosuppression
434
Which 2 side effects of chemotherapy are patients most concerned about?
Nausea and vomiting
Hair loss
435
bone marrow = organ most commonly affected by chemo and
myelosuppression = dose limiting tox for most chemo drugs, 2 exceptions
vincristine
bleomycin
436
Why does neutropenia, thrombocytopenia and anaemia occur with chemotherapy?
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
predisposing factors to neutropenia and infection (most important haematological tox due to risk of life threatening infection)?
- depth + duration of neutropenia
- loss of cell-mediated and humoral immunity
- mucosal damage
438
What does a longer nadir duration mean?
Greater risk of developing serious infection.
439
Why is G-CSF given before SCT?
management of neutropenia
to stimulate new stem cells
440
How is neutropenia managed?
G-CSF
prophylactic antibiotics or anti-fungals
441
if px presents with neutropenia and fever, need prompt treatment with what?
broad spec antibiotics
442
what drugs may be given as prophylaxis for px going through chemo?
antibiotics
443
3 effects of cytotoxic drugs on GI tract?
nausea and vomiting
oral mucositis
diarrhea
444
How are nausea and vomiting categorised in 3?
Acute (first 24 hours)
Delayed (24 hours onwards)
Anticipatory
445
nausea and vom management through which 2 drug classes?
5HT3 receptor antagonists
NK1 antagonists
446
Give 2 examples of dopamine antagonist anti-emetics?
metoclopramide
domperidone
447
Give an example of a 5-HT3 antagonist anti-emetic?
ondansetron
448
Give an example of an antihistamine anti-emetic?
cyclizine
449
Give an example of an NK1 antagonist anti-emetic?
aprepitant
450
Give an example of anticholinergic anti-emetic?
hyoscine hydrobromide
451
Give an example of a corticosteroid anti-emetic?
dexamethasone
452
4 divisions of emetogenicity of chemo regimens?
high emetogenic risk
moderate
low
minimal
453
4 divisions of emetogenicity of chemo regimens?
high emetogenic risk
moderate
low
minimal
454
What chemotherapy regimens are highly emetogenic?
SCT schedules
cisplatin based
455
What chemotherapy regimens are minimal emetogenic?
vincristine
bleomycin
456
What risk factors make pts more prone to nausea and vomiting?
young age
female
previous motion/morning sickness
457
metoclopramide + dexamethaone = example of what division of emetogenicity?
moderately
458
symptoms of oral mucositis
pain
dry mouth
altered taste
ulceration
459
how is oral mucositis treated?
mouthwashes
topical steroids
sucralfate
mucaine
lignocaine gel
sucking ice cubes: lower blood supply
460
5FU
MTX
anthracyclines
cytarabine
are common culprits of what SE?
oral mucositis
461
How is chemotherapy associated diarrhoea managed?
loperamide: may need to exceed usual max dose
codeine
octreotide if v severe
462
what 2 drugs often -> diarrhea?
5FU
irinotecan
also occurs with majority of nibs
463
main concern with conventional chemo: alopecia.
how is this prevented?
scalp cooling
464
alopecia often seen with
T
A
E
B
I
taxanes
anthracyclines
etoposide
bleomycin
ifosfamide/ cyclophosphamide
465
3 Symptoms of PPE/ hand-foot syndrome?
tenderness
tingling
peeling skin
466
how is PPE managed?
dose interruption and reduction
chiropody
cushion based footwear
467
How is tumor lysis syndrome prevented with allopurinol?
Allopurinol prevents the formation of uric acid
but no effect on existing urate
468
Why might (rasburicase) recombinant urate oxidase be given in tumour lysis syndrome?
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
What class of cancer drugs can cause temporary infertility in men?
Alkylating agents
470
What service is offered to men who undergo chemotherpy prior to it?
Sperm banking
471
What are the two main effects chemotherapy has on ovaries?
amenorrhoea
menopausal symptoms
472
What strategies are used to maintain fertility in women receiving chemotherapy treatment?
IVF
egg freezing
ovarian tissue freezing
473
Pulmonary toxicity is most commonly seen with what cancer therapy drug?
bleomycin
474
Nephrotoxicity is most commonly seen with what cancer therapy drugs?
Cisplatin
Ifosfamide
Methotrexate
475
pukmonary tox is more likely with IV bolus or long infusion?
IV bolus
476
busullfuran, MTX, carmustine are 3 other drugs that can damage what?
lungs
477
nephrotox can cause renal tox and ...
electrolyte disturbances
478
for high dose MTX alkalinise urine to prevent what?
drug precipitating in renal tubules
479
Neurotoxicity is most commonly seen with what cancer therapy drugs?
Cisplatin
Oxaliplatin
Vinca alkaloids
Thalidomide
480
neurotox may cause what 2 types of neuropathy?
peripheral: pins and needles
autonomic: constipation
481
Which vinca alkaloid is most likely to cause neurotoxicity?
Vincristine
482
neurotox likely associated with high doses and long term usage so doses capped at what?
2mg
483
Cardiotoxicity is most commonly seen with what cancer therapy drugs?
antharacyclines
484
cardiotox main concern is HF, related to what?
cumulative tox
485
dexrazoxane (free radical scavenger) is used to try and prevent cardiotox via long infusions or alt drugs such as
mitoxantrone
486
side effects of novel therapies?
infusional tox with mabs
rash with EGFR
HTN with VEGF targets
immun e related w CPI
487
What do the side effects of checkpoint inhibitors usually affect?
How long do they take to appear?
Skin
GI tract
weeks to months
