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411 Oncology > L6 - Principles of systemic anticancer treatment > Flashcards

L6 - Principles of systemic anticancer treatment Flashcards

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1
Q

What are the SIX possible approaches to cancer management?

A 
Surgery
Radiotherapy
Chemotherapy
Endocrine therapy
Targeted therapy
Immunotherapy
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2
Q

What are the main TWO goals when CURING cancer?

A

Destroy all cancer cells

Prevent recurrence

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3
Q

What are the main FOUR goals when CONTROLLING cancer?

A

Shrink tumour

Prevent tumour from growing & spreading further

Improve quality of life

Possibly prolong life

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4
Q

What are the main TWO goals when providing cancer PALLIATION?

A

Reduce & relieve cancer symptoms

Improve quality of life

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5
Q

What are the SEVEN types of chemotherapy/cytotoxic treatment?

A

Alkylating agents

Anthracyclines

Antimetabolites

Vinca alkaloids

Taxanes

Platinum compounds

Antibody-drug conjugates

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6
Q

What are the THREE types of non-cytotoxic treatment?

A

Endocrine therapy

Targeted therapy –> tyrosine kinase inhibitors

Immunotherapy –> monoclonal antibodies (checkpoint inhibitors)

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7
Q

What is adjuvant chemotherapy?

A

Given after surgery to reduce risk of relapse

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8
Q

What is neoadjuvant chemotherapy?

A

Given to shrink tumour enough to allow curative/less invasive surgery

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9
Q

What is palliative chemotherapy?

A

Given to relieve cancer symptoms, improve quality of life, possibly prolong life

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10
Q

When is chemotherapy most effective?

A

Proliferating cells, in M-phase (ie. when cells are dividing)

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11
Q

What are FIVE ways in which chemotherapy works?

A

Prevent cell replication

Inhibits synthesis of new DNA strands

Blocks formation of nucleotides necessary to create new DNA

Stops mitosis & cell division

Causes cell damage which leads to apoptosis

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12
Q

Why is chemotherapy typically given in 2/3 week cycles?

A

Timespan for neutrophils to come back up to safe levels for next chemotherapy cycle

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13
Q

What is chemotherapy dosing based on?

A

Body surface area (BSA)

BSA = square root [ (height cm x weight kg) / 3600 ]

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14
Q

When are dose modifications for chemotherapy doses (when calculated by BSA) needed?

A

Performance status, age, frailty

Kidney/liver function

Toxicity during cycles –> adjust dose for next cycle

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15
Q

Which cell cycle phase do taxanes work in?

A

M-phase (mitosis)

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16
Q

How do taxanes work?

A

Bind to microtubules & stabilise their structure

  • -> Prevent anaphase
  • -> Prevent cell division
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17
Q

What are examples of taxanes?

A

Docetaxel

Paclitaxel

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18
Q

What are examples of antimetabolites?

A

Cytarabine

Methotrexate

Gemcitabine

Fluorouracil (5FU)

Capecitabine

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19
Q

Which cell phase do antimetabolites work in?

A

S-phase (synthesis of DNA)

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20
Q

How do antimetabolites work? (general)

A

Substitute themselves for essential metabolites

–> Prevent DNA & RNA synthesis

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21
Q

What are examples of folate antagonists? (antimetabolites)

A

Methotrexate

Pemetrexed

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22
Q

How does methotrexate work? (antimetabolite)

A

Inhibits conversion of folic acid –> folinic acid by dihydrofolate reductase

Folinic acid needed for DNA replication

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23
Q

How does pemetrexed work? (antimetabolite)

A

Inhibits multiple enzymes involved in folate metabolism (inc. dihydrofolate reductase like methotrexate)

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24
Q

When is it preferred to give folic acid over folinic acid?

A

Smaller methotrexate doses

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25
When is it preferred to give folinic acid over folic acid?
Larger methotrexate doses
26
Why is folinic acid important if methotrexate is being used?
Co-factor for DNA replication --> causes apoptosis when inhibited If not supplemented following methotrexate administration, deficiency can cause mucositis, neutropenia etc.
27
How does fluorouracil (5FU) work? (antimetabolite)
``` Pyrimidine analogue (actual nucleotide found in DNA) --> "Fraudulent nucleotide" inhibits thymidylate synthetase, enzyme essential in DNA synthesis ```
28
What is the prodrug of fluorouracil (5FU)?
Capecitabine
29
How does folinic acid work with fluorouracil (5FU)?
Increases 5FU toxicity/efficacy --> stabilises complex with thymidylate synthetase
30
What are examples of anthracyclines?
Doxorubicin Epirubicin
31
What cell phase do anthracyclines work in?
NON-phase specific
32
How do anthracyclines work?
Intercalation of base pairs in DNA double helix - -> Alkylation of DNA by free radicals - -> DNA strand breaks by inhibition of topoisomerase II (unwinding enzyme) - -> No transcription allowed - -> Inhibit DNA replication
33
What are examples of alkylating agents?
Cyclophosphamide Ifosfamide
34
What cell phase do alkylating agents work in?
NON-phase specific
35
How do alkylating agents work?
Add alkyl groups to nucleic acids, proteins, amino acids, nucleotides - -> Crosslink DNA strands ("extra ladder rungs") - -> Prevent strand separation & unwinding - -> Widespread cell damage --> apoptosis
36
What are examples of platinum compounds?
Cisplatin Carboplatin Oxaliplatin
37
What cell phase do platinum compounds work in?
NON-phase specific
38
How do platinum compounds work?
Add alkyl groups to nucleic acids, proteins, amino acids, nucleotides - -> Crosslink DNA strands ("extra ladder rungs") - -> Prevent strand separation & unwinding - -> Widespread cell damage --> apoptosis
39
What cell phase do platinum compounds work in?
NON-phase specific
40
Because cisplatin is highly emetogenic, nephrotoxic & ototoxic, what else needs to be given along with its administration?
Fluids --> lots to flush drug through while minimising adverse effects Monitor
41
Although carboplatin is more tolerable than cisplatin (less emesis/nephrotoxicity/ototoxicity), what does it have a higher risk of?
Myelosuppression (decreased bone marrow activity) Neutropenia (low WBC) Thrombocytopenia (low platelets)
42
What formula is used to calculate carboplatin dosing?
Calvert formula --> based on CrCl, since carboplatin is almost exclusively excreted renally
43
What is the main way of excretion of carboplatin
Renal excretion
44
Which sort of cancer is oxaliplatin indicated for?
GI cancers. eg. colorectal
45
Although oxaliplatin has the safest side profile compared to cisplatin & carboplatin, what does it have a higher risk of?
Cold-induced neuropathy - Tingling etc. even when touching cold things, drinking cold drinks Caution, esp. few days after chemo
46
Adverse effects of chemotherapy are split into what phases?
Immediate Early onset Late onset
47
What are TWO types of immediate adverse effects of chemotherapy?
Extravasation Hypersensitivity reactions
48
What are SEVEN types of early onset adverse effects of chemotherapy?
Haematological Gastrointestinal --> mucositis, constipation, diarrhoea, nausea & vomiting Dermatological --> eczema, psoriasis, SJS Nephrotoxicity, hepatotoxicity Myalgia (esp. with taxanes) Neuropathy Alopecia
49
What are FIVE types of late onset adverse effects of chemotherapy?
Cardiac toxicity (esp. with anthracyclines) Pulmonary toxicity Neurotoxicity (esp. with vinca alkaloids) Loss of fertility Secondary malignancies --> most cytotoxic drugs are carcinogenic, since many cause DNA damage
50
What is haematological toxicity? (early onset)
Most frequent toxicity --> may be dose-limiting
51
What are the THREE types of haematological toxicity?
Neutropenia --> neutrophils Thrombocytopenia --> platelets Anaemia --> RBCs
52
What is thrombocytopenia?
Low platelets
53
What does thrombocytopenia result in?
Increased bleeding risk --> low platelets means clotting decreased
54
How can thrombocytopenia be treated?
Platelet infusion
55
What is anaemia?
Low haemoglobin in RBCs
56
What are TWO common symptoms of anaemia?
Fatigue Shortness of breath
57
How can anaemia be treated?
RBC transfusion (epoetin alfa)
58
Why is neutropenia most dangerous?
Occurs relatively quickly (short neutrophil lifespan) Increased susceptibility to infection May cause delay/dose reductions
59
How can neutropenia (not febrile) be treated or prevented?
G-CSF - Filgrastim - Pegfilgrastim
60
What is the difference between filgrastim & pegfilgrastim?
Pegylated version increases molecule size - -> Harder to metabolise/break down - -> Longer half-life & duration of action - -> Reduced dosing frequency Filgrastim preferred in shorter chemo cycles eg. 1-2 weekly --> cleared fast enough for next dose Pegfilgrastim required at least 14 days before next chemo cycle
61
Why are G-CSF treatments not used in acute myeloid leukaemia?
Neutrophils come from the myeloid line --> in leukaemia, there are too many WBC. G-CSF stimulates blood cell growth --> may increase risk of blood cancer
62
What temperature is considered febrile neutropenia?
38.3°C & low neutrophil count < 0.5 x 10⁹/L
63
How can febrile neutropenia be treated?
[guidelines] Empiric antibiotics G-CSF --> if no improvement after 48 hours
64
What investigations are involved in a "septic screen"?
Blood cultures Midstream urine sample Chest xray
65
What are the THREE phases of chemo-induced nausea & vomiting
Acute onset Delayed onset Anticipatory
66
Which FOUR chemotherapy drugs have HIGH emetogenic risk?
Cisplatin Dacarbazine Anthracycline/cyclophosphamide combination High-dose cyclophosphamide
67
Which FOUR chemotherapy drugs have MODERATE emetogenic risk?
Carboplatin Epirubicin Irinotecan Oxaliplatin
68
Which FOUR chemotherapy drugs have LOW emetogenic risk?
Docetaxel Paclitaxel Fluorouracil Methotrexate
69
Which TWO chemotherapy drugs have MINIMAL emetogenic risk?
Vinorelbine Vincristine
70
What FOUR drugs are used for HIGH emetic risk with chemotherapy?
Aprepitant Olanzapine --> dopamine receptors also targeted by antipsychotics Dexamethasone Ondansetron
71
What TWO drugs are used for MODERATE emetic risk with chemotherapy?
Dexamethasone Ondansetron
72
What TWO drugs are used for LOW emetic risk with chemotherapy?
Dexamethasone Ondansetron
73
Which TWO types of emesis does dexamethasone work on?
Acute onset Delayed onset
74
Which TWO types of emesis does aprepitant work on?
Acute onset Delayed onset [only for highly emetic chemo]
75
Which ONE type of emesis does ondansetron work on?
Acute onset
76
Which TWO types of emesis does olanzapine work on?
Acute onset Delayed onset
77
Which ONE type of emesis does lorazepam work on?
Anticipatory --> helps calm patient down Usually if have had bad experiences with chemo before --> psychological
78
Which chemotherapy drugs usually cause diarrhoea?
Capecitabine Irinotecan Less commonly fluorouracil, docetaxel
79
What is the THREE step treatment plan for chemotherapy-induced diarrhoea?
Loperamide (higher doses than normal) Codeine Octreotide (continuous SC infusion) --> usually nil by mouth when on chemo --> total parenteral nutrition may be needed to reduce malnutrition
80
How do monoclonal antibodies work? (TWO ways)
Stimulate patient's immune system to destroy target Prevent growth by blocking target
81
What is the most common ADR with monoclonal antibodies?
Infusion-related --> allergic
82
What are the THREE types of immune checkpoint inhibitors?
PD-1 inhibitors --> nivolumab, pembrolizumab PD-L1 inhibitors --> atezolizumab CTLA-4 inhibitors --> ipilimumab
83
What does it mean when the Death Star is firing at Alderaan?
Tumour cells destroying normal cells. Activity not inhibited
84
What does it mean when Admiral Ackbar is telling the Rebels about the Death Stars deflector shield?
Tumour cells have mechanisms to stop T cells from attacking them
85
How does PD-1 & PD-L1 work?
PD-1 (T cell) usually binds to PD-L1 (normal cell) & this inactivates T cells --> do not attack Tumour cells able to express PD-L1 --> T cell inactivated & tumour cell free to replicate/grow
86
What does it mean with Han, Luke & Leia?
Deflectors shields need to be brought down by them on the forest moon of Endor Checkpoint inhibitors
87
How do checkpoint inhibitors work?
Block binding of PD-1 & PD-L1 - -> T cell not inactivated by tumour cell - -> T cell can continue attacking tumour cells
88
What does it mean when the Millenium Falcon destroys the Death Star's exhaust port?
T cell attacking & destroying tumour cell
89
What are the TWO main adverse effects of immunotherapy & TWO less common ones?
Immune-related adverse effects Fatigue Less common: nausea, low blood counts
90
What are FIVE examples of immune-related adverse effects?
Hormonal effects --> eg. initial hyperthyroidism flare then persistent hypothyroidism Hepatitis, nephritis Pneumonitis --> breathlessness, cough Colitis --> diarrhoea Skin rash, itch
91
What are the grades for immune-related adverse effects?
1: Mild 2: Moderate 3: Severe 4: Life-threatening
92
How are the different grades of immune-related adverse effects managed?
1: Treat symptomatically; continue with checkpoint inhibitors 2: Withhold checkpoint inhibitor, start prednisone. Resume checkpoint inhibitor when symptoms return to grade 1 3 & 4: Permanently discontinue checkpoint inhibitor, start higher prednisone dose If ADRs not resolved with prednisone, consider infliximab or mycophenolate (for hepatitis)
93
How are other immune-related adverse effects (eg. hypothyroidism & hyperthyroidism) managed?
Hypothyroidism: levothyroxine Hyperthyroidism: watch & wait --> generally initial flare followed by persistent hypothyroidism
94
What does hypercalcaemia as a complication of cancer lead to?
Drowsiness Confusion Osteoporosis Risk of cardiac arrhythmias
95
How is hypercalcaemia as a complication managed?
Rehydration --> fluids Zoledronic acid, pamidronate
96
Why is zoledronic acid preferred over pamidronate for hypercalcaemia?
100x more potent Less frequent administration Shorter duration of infusions

411 Oncology (9 decks)

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