cancer simplified Flashcards
(132 cards)
1
Q
Mechanism of action of methotrexate
A
- inhibits dihydrofolate reductase (DHFR) → blocks conversion of dihydrofolate to tetrahydrofolate.
- A depletion of tetrahydrofolate leads to thymidylate deficiency which is vital for DNA synthesis. 3. This inhibits DNA synthesis, particularly in rapidly dividing cells and leads to cell death.
2
Q
What phase is methotrexate and 5FU(capecitabine) specific to
A
S-phase
3
Q
What is the dose limiting toxicity of methotrexate
A
Bone marrow suppression
4
Q
What group of chemotherapy agents cause oral mucositis
A
Mainly antimetabolites
5
Q
What drugs are high risk for alopecia
A
- Methotrexate
- Anti Microtubules agents(taxanes and vincaalkaloids)
- Anthracyclines(doxorubicin)
6
Q
What is the kidney supportive care for methotrexate
A
Pre and post treatment hydration: IV fluids including 100mEq HCO3- until urine pH is 7 and maintain this pH throughout therapy
7
Q
What is Leucovorin and when is it given
A
Folinic acid.
Give 24 hours after MTX chemotherapy, to reduce side effects and save bone marrow cells . Also used and rescue therapy in MTX overdose
8
Q
What is the emesis risk of methotrexate
A
Minimal = Oral MTX
Low < 250mg/m2
Moderate > 250 mg/m2
9
Q
What is the extravasation risk of methotrexate
A
Irritant
10
Q
What do you monitor with methotrexate
A
FBC
MTX concentration at 24 hours.
Bilirubin and LFT(hepatoxic)
* temporary rise between doses but not true liver impairment
Renal function tests baseline and every cycle
11
Q
What is mechanism of action of 5-FU
A
Inhibits thymidylate synthase + additional mechanism
1. 5FU converted to metabolite FdUMP
2. FdUMP binds thymidylate synthase
3. Fluorine ion prevents reaction from occurring thus forms stable complex with thymidylate synthase and co-factor tetrahydrofolate.
4. No synthesis of DNA precursors: purine and pyrimidines
5. apoptosis
additional mechanism: to incorporate into DNA and RNA disrupting normal functioning and processes(poorly understood)
12
Q
What is the dose limiting toxicity of capecitabine
A
Diarrhoea (leads to dehydration and renal failure)
Bone marrow suppression(if given by IV bolus)
13
Q
What is the emesis risk of 5FU and capecitabine
A
LOW
14
Q
How do you treat diarrhoea associated with capecitabine
A
- Loperamide
- Oral Rehydration Sachets,
- Codeine(add/replace lop)
- if severe(grade 3-4) give octreotide(somatostain analogue which reduces GI motility)
15
Q
What deficiency should be tested for on capecitabine
A
Dihydropyrimidine dehydrogenase deficiency before initiating treatment
DPD metabolises capecitabine, if there is deficiency higher risk of toxicities, contraindicated.
16
Q
What are non dose limiting toxicities of capecitabine
A
- mucositis
- Peripheral neuropathy
17
Q
What 4 drugs causes peripheral neuropathy
A
- Vincristine
- Capacitabine
- Paclitaxel
- Cisplatin
18
Q
How do you manage peripheral neuropathy caused by chemotherapy
A
Pyridoxine 50mg PO TDS
Transcutaneous Electrical Nerve Stimulation(TENS)
Acupunture
Severe - gabapentin or pregabalin
19
Q
What are the symptoms of peripheral neuropathy
A
Change in sensation
Increased sensitivity
Pain
Numbness
Muscle weakness
Coordination or balance issues
Loss of finger movement
20
Q
What is the difference between capecitabine and 5FU
A
capecitabine is oral prodrug of 5FU, it is converted to 5FU in 3 stages by enzymes which are higher in cancerous cells which makes it more specific.
21
Q
What drug class is cyclophosphamide
A
Alkylating agent
22
Q
Is cyclophosphamide and prodrug
A
Yes
23
Q
Are alkylating agents and alkylating like agents cycle specific
A
No
DNA can be accessed at any point
24
Q
What is the dose limiting toxicity of cyclophosphamide
A
Bone marrow suppression
25
What are other toxicities of cyclophosphamide
Hemorrhagic cystitis
26
What is hemorrhagic cystitis
Hemorrhagic cystitis irritation of the bladder lining caused by breakdown product called acrolein
27
What is the emesis risk of Cyclophosphamide
> 1500mg/m2 High emesis risk >90% incidence
<1500mg/m2 Moderate emesis risk (30-90%)
28
What is the extravasation risk of cyclophosphamide
Non-vesicant (nuetral)
29
When do you give aprepitant
Anthracycline+ cyclophosphamide
High dose cisplatin (70mg/m2)
30
What is hemastix
Testing for blood in urine
31
What is mesna
Mesna binds to acrolein and removes it.
32
When is mesna given prophylactically
Mesna is always given to patients receiving cyclophosphamide doses of 1g/m2 or more (can be oral or iv), and all doses of ifosfamide
33
What is the mechanism of action of cyclophosphamide
It binds to the N7 position of guanine and forms cross links either intrastrand or interstrand. Interstrand crosslinks prevent the DNA from being unwound thus stopping DNA transcription and replication from occuring --> apoptosis
34
What treatment may be used to treat neutropenia
immediate admission for broad-spectrum antibiotic therapy (piperacillin-tazobactam & gentamicin)
Granulocyte-colony stimulating factor(GCSF) i.e filgrastim Stimulates the production of neutrophils.
35
What class is mephalan
Alkylating agent
36
What is the mechanism of action of melphalan
It binds to the N7 position of guanine and forms cross links either intrastrand or interstrand. Interstrand crosslinks prevent the DNA from being unwound thus stopping DNA transcription and replication from occuring --> apoptosis
37
Dose limiting toxicity of melphalan
Bone marrow suppression
38
What is the emesis risk of melphalan
Moderate risk if dose above 100mg/m2
Minimal risk if oral therapy
39
What enzyme does doxorubicin inhibit
Topoisomerase II
40
What is the role of Topoisomerase II
Maintaining the integrity of DNA and regulating the coiling of DNA
41
Doxorubicin 3 MOA's
1. Stabilises Topo2 and DNA complex (transient breaks cannot be resealed)
2. Intercalates into DNA bases, disrupting the helical structure
3. Produces reactive oxygen species, that cause DNA damage
42
is doxorubicin cell cycle specific
Non -cycle specific
43
What is the dose limiting toxicity for doxorubicin
Cardiotoxicity
-oxygen free radicals usually detoxified by catalase but heart has low catalase activity
44
What is doxorubicin cardiotoxicity cumulative lifetime dose
around 450 -550mg/m2
45
What is a non toxic side effect of doxorubicin
colours urine red
46
What is the emesis risk of doxorubicin
LOW risk for liposomal doxorubicin
MODERATE = < 60mg/m2
HIGH = > 60mg/m2 OR given with cyclophosphamide
47
What is extravastion risk with doxorubicin
DNA binding vesicant
Doxorubicin is a bright red solution
48
What are the two types of vesicants and the difference between them
DNA binding or non-DNA binding.
bind to DNA --> cell death, drug then released --> further more extensive damage
doesnt bind to DNA --> get metabolised in tissue--> local damage
49
How do you treat extravasation of DNA BINDING vesicants (LN)
1. stop the infusion but leave cannula in place
2. aspirate the area
3. Mark the extravasated area with a pen
5. remove cannula
6. COLD (constricts vessels stops spread) compress 20mins QDS for 1-2 days
7. Neutralise - Use specific antidotes(Anthracyclines- dexrazoxane)
8. elevate limb+ analgesia
50
How do you treat extravasation of NON-DNA BINDING vesicants (Disperse and Dilute)
1. stop the infusion but leave cannula in place
2. aspirate the area
3. Mark the extravasated area with a pen
5. remove cannula
6.warm (speed up distribution for metabolism) compress 20mins QDS for 1-2 days
7. dilute - hyaluronidase (vinca alkaloids and taxanes)
8. elevate limb+ analgesia
51
How do you treat extravasation of irritant
1. stop the infusion but leave cannula in place
2. aspirate the area
3. Mark the extravasated area with a pen
5. remove cannula
6. Saline flush out
52
How do you treat extravasation of non-vesicant
1. Local dry cold compress
2. elevate and pain relief
53
What should you monitor for doxorubicin
FBC, LFT, U&Es
ECG every 3 months of treatment
MUGA scan (LVEF )
Baseline MUGA is the are predisposed to heart failure, have hypertension or are a smoker.
54
What is MUGA scan
radioactive tracer injected into blood stream and a GAMMA camera is used to see how blood is being pumped through the heart and left ventricular ejection fraction (LVEF) is measured
55
What type of drug is Etoposide
Non-anthracycline Topoisomerase II inhibitors
56
Etoposide MOA
stabilize topoisomerase II DNA complex, preventing DNA from re-sealing and leading to double strand breaks
- The accumulation of DNA double strand breaks leads to apoptosis
57
What part of the cycle is etoposide specific to
S and G2 phases
58
What is the extravasation risk with etoposide
irritant
59
What happens is etoposide is infused too quickly
Low blood pressure
60
What are the two dose limiting toxicities of etoposide
Mucositis at high doses
Myelosuppression
61
What 2 drugs are microtubules inhibitors
Vincristine
Paclitaxel
62
Vincristine MOA
Inhibits microtubule polymerization by binding to beta-tubulin, thus preventing the assembly of microtubules
-This disrupts formation of mitotic spindle = leads to metaphase arrest and eventual apoptosis of rapidly dividing cells
63
What cell cycle phase is vincristine and paclitaxel specific to
M-phase
64
What is the extravasation risk of Vincristine
Non-DNA binding vesicant
65
emesis risk of vincristine
minimal risk(Less than 10%)
66
How does vincristine affect LFTs
transient rise post treatment
67
What supportive care with vincristine
- Cold cap
- GCSF
- Peripheral
- Neuropathy (pyridoxine)
68
Dose limiting toxicity of vincristine
Peripheral Neuropathy
+
Nuetropenia
69
What class of drug is bleomycin
Cytotoxic antibiotic
70
Bleomycin 2 mechanism of action
1. Bleomycin forms a complex with Fe2+(pseudoenzyme). This complex under goes redox reactions to form superoxide and hydroxide free radicals that cleave DNA.
2. Inhibit DNA polymerase a key enzyme required for DNA synthesis.
71
What phase is bleomycin specific to
G2 phase
72
What is the dose limiting toxicity of bleomycin
Pulmonary toxicity (pulmonary fibrosis)
73
What is monitoring for bleomycin
Chest X-ray
Lung function tests
Respiratory symptoms
renal function - reduce dose
74
Bleomycin extravasation risk?
Non- vesicant
75
Bleomycin emesis risk
minimal
76
Paclitaxel MOA
Binds to beta-tubulin and stabilizes it (stabilizes microtubules), which prevents microtubule disassembly, and essentially locks them in place = disrupts cell division and induces apoptosis
77
Dose limiting toxicity of paclitaxel
Neutropenia
78
paclitaxel emesis risk
low/moderate(idk not in list)
79
Paclitaxel extravasation risk
Non-DNA binding vesicant
80
Paclitaxel is high risk of what non-toxic side effect
Alopecia
81
what component in paclitaxel causes hypersensitivity reactions
Cremophor EL
82
What 3 premedication is given with paclitaxel to prevent hypersensitivity reactions
Dexamethasone Antihistamine(chlorpheniramine)
H2 antagonist (famotidine)
83
What is the mechanism of action of cisplatin
Enters cells via passive diffusion and CTR1
- aquation where Cl- ligands replaced with water (aqua-ligand displacement) and becomes positively charged. binding to to N7 guanine of DNA, where it forms intra-strand and inter-strand cross links (DNA is negatively charged and can bind to positively charged ligand complex) = preventing DNA replication and transcription (predominantly intra-strand)
84
What is the dose limiting toxicity of cisplatin
Nephrotoxicity
85
What are the 3 toxicity of cisplatin(excluding nephrotoxicity)
1. Ototoxicity(hearing loss)
2. Peripheral neuropathy
3. Bone marrow suppression
86
What is the emesis risk for cisplatin
more than 70mg/m2 high emesis risk(90%+incidence)
less than 70mg/m2 moderate emesis risk (30-90% incidence)
87
Cisplatin extravasation
Irritant
88
What is the supportive care for cisplatin
Pre and post IV fluids for hydration + Furosemide or mannitol
Antiemetics
89
What monitoring is there for cisplatin
1. CrCL + U & E
2. LFT + Billirubin
3. Hearing tests(Ototoxicity)
4. FBC
5.Signs of peripheral nueropathy
90
What is tamoxifen
A selective oestrogen receptor modulator
91
When is oestrogen used
For ER+ breast cancers(Pre/post menopausal women)
Either pre or post debulking to prevent recurrence
92
Tamoxifen MOA
Oestrogen stimulates proliferative signalling that enables cells to enter the mitosis especially in breast tissue. In ER+ breast cancers oestrogen causes uncontrolled proliferative signalling leading to tumour growth. Tamoxifen is structurally similar to estrogen, such that it can bind to the oestrogen receptor. However, it produces antagonistic effects, as it prevents endogenous estrogen from binding as a result, preventing proliferative signalling such that cells remain static cannot progress into the cell cycle.
93
What phase does tamoxifen act
G0/ G1 phase
94
What is DLT of tamoxifen
Does not have DLT
95
What toxicities of tamoxifen
Hot flushes, irregular menses and discharge.
Thromboembolism(VTE and PE)
Increased risk of endometrial cancer(agonistic effects)
96
Emesis risk of tamoxifen
Low(less than 10% incidence)
97
Extravasation risk of tamoxifen
No risk as Oral
98
Supportive therapy for tamoxifen
Regular breast screening
Stockings on flights
Hot flush/sweats - l/s advice like menopause
Vaginal dryness - non-hormonal lubricants
Mood swings - SNRIs
99
What is herceptin
Humanised monoclonal antibody trastuzumab
100
What is the dose limiting toxicity of herceptin
Cardiotoxicity(Heart failure and LVEF)
LVEF must be above limit
101
Why does herceptin cause cardiotoxicity
Down regulates neuregulin which maintains cardiac functioning
102
What should monitor with herceptin
LVEF(baseline and before each cycle)
Signs of heart failure(SOB etc)
103
What is gleevec
A tyrosine kinase inhibitior
Imatinib
104
How does gleevec work
It works by binding to the ATP binding site of tyrosine kinase, which is important for the phosphorylation of tyrosine residues which initiates downstream signalling.
105
What phase of the cell cycle does trastuzumab act
Cellular arrest at the G1
106
What is supportive therapy for imatinib
Adequate hydration and allopurinol 300mg OD to prevent tumour lysis syndrome
107
What is tumour lysis syndrome?
Tumour lysis syndrome is a metabolic disorder caused by destruction of malignant cells.
This results in derangement of electrolytes
108
What electrolyte derangements are seen in tumour lysis syndrome
High uric acid
High potassium
High phosphate
Low calcium
109
What can untreated tumour lysis syndrome result in
Renal damage, arrythmias, seizures and death
110
How is tumour lysis syndrome prevented
Prophylaxis: allopurinol 300mg OD
Burkitts lymphoma: rasburicase for treatment and prevention
111
What 2 patient groups are at an increased risk of TLS
Older patients
Impaired renal function - cannot clear electrolytes
112
What is used to treat tumour lysis syndrome
Allopurinol/Rasburicase
Fluids i.e calcium gluconate, insulin dextrose
If kidneys very impairmed may require dialysis
113
What cancers pose a higher risk of TLS
Haematological cancers
Cancers which large tumour burdens such as Burkitts lymphoma and non- Hodgkins lymphoma
114
Why is TLS mainly associated with the 1st cycle of chemotherapy
the tumour is at its largest at the first cycle, more cells lysing
115
How can you minimise cardiotoxicity from anthracyclines
1. Minimise overall dose exposure
2. Use slow infusion vs bolus
3. Liposomal formulations accumulate in tumour rather than heart
4. use of ACE inhibitors, ARBs and beta blockers.
5. Dexrazoxane - chelates iron and reduces production of free radicals
116
Why is slower infusion better than bolus
Slower infusion reduces sudden increase of free radicals produced. the body has more time to neutralise harmful species
117
What LVEF should you stop using trastuzmab and anthracyclines
Do not use trastuzmab if LVEF drops below 50%
Anthracyclines – stopped at 60% reduction in LVEF, higher due to delayed cardiotoxicity
118
What is plantar palmar erythema
Side effect of chemotherapy, affecting the palms of the hands and soles of the feet, causing redness, pain or discomfort in these areas. In severe cases the skin on the hands and feet can crack, blister or peel.
119
What are 6 counselling points for PPE
Keep skin well moisturised with emollient cream to maintain barrier repair.
Pat hands dry do not rub.
Protect against irritants, e.g. use gloves when washing up.
Avoid exposure to sun or excessively hot water.
Keep feet bare whenever possible, or wear cotton socks and low-heeled, soft, snug-fitting shoes.
Keep skin cool when possible but avoid extremes of heat.
Leave blistered skin to heal.
120
In metastatic/palliative chemo should you reduce dose/stop treatment if PPE occurs
palliative patients we would want to keep comfortable so reduce dose to not impact quality of life
121
How do you manage pain in peripheral neuropathy
Antipyretics(Ibuprofen and paracetamol) not normally given as they may mask symptoms of fever which may indicate low WBC - must monitor patients if on.
NSAIDS should be avoided if patient thrombocytopenic as increases bleed risk.
Use pregablin and gabapentin.
122
What is mucositis
Damage to the mucosal lining of the GI tract.
there is a high risk of infection, patient suffer from reduce oral intake and pain
123
Mucositis prophylaxis
Good oral hygiene
Use soft toothbrush for all patients to avoid breaking the gum.
May use Corsodyl® (chlorhexidine).
Nystatin may given for prevention
Sugar free gum or suck on ice cube for dry mouth
Moist soft foods – soups, jelly, soft fruit.
124
Mucositis treatment
Difflam® MW(benzylamine hydrochloride) - Reduces local inflammation, numbs area, antiseptic for mild infection prevention
Sucralfate suspension - chalky barrier, tastes bad
Lignocaine - local anaesthetic, bites tongue - not often used
Paracetamol
Anti-metabolite induced folinic acid rescue
124
What the 3 commonly used limits in chemotherapy for cell counts
Platelets: 100 x10^9 cells/L
white cell count: 3 x10^9 cells/L
Neutrophil count: 1.5 x10^9 cells/L
125
5 symptoms of bone marrow suppression
Unexplained bleeding and bruising
Sore throat
Fever
Fatigue
Breathlessness
126
Neutropenia sepsis
Occurs when a neutropenic person develops a life threatening infection.
Neutrophil count is lower than 0.5 with a temperature and signs of sepsis(shivering, sense of doom, clammy hands, SOB)
127
What is the difference between neutropenic sepsis and febrile neutropenia
Febrile neutropenia does not have signs of sepsis.
but are at an high risk of sepsis
128
How to treat neutropenia
GCSF
- stimulates the product of neutrophils
129
What are the two reasons for using GCSF
**Primary prevention** - where we **anticipate** the patient will experience neutropenia therefore we give it from the first cycle to prevent an intial neutropenia from occuring at the nadir which is 7 days post chemo. This prevents the next cycle from being delayed - so mainly used for curative chemo
**Secondary prevention** is where we start GCSF after the patient experiences neutropenia and then we use it for subsequent cycles to prevent another episode. Secondary prevention is mainly used for metastatic/palliative regimens as we would instead reduce doses of cytotoxic agent.
130
Treatment for thrombocytopenia
Platelet transfusions as it is hard to raise platelets.
Can result in cycle delay and dose reductions as there is a limit to amount of transfusion that can be given.
Stop anti-platelets such as aspirin and LWHM
131
Treatment for anaemia
Iron tablets
Blood transfusions if very low - but pts can become transfusion dependent which can lead to iron overload
