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Oncology 6 Flashcards

1
Q

What are the consequences of not controlling CINV?

A

medical complications
-elyte imbalances, dehydration
poor QoL
poor adherence
dose reductions; tx delays
poor outcomes

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2
Q

What is the goal with treatment of CINV?

A

no emesis
no (or mild) nausea

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3
Q

How are the goals of CINV achieved?

A

reassess efficacy prior to each cycle
for maximal benefit, initiate anti-emetics prior to chemotherapy
scheduled anti-emetics vs prn

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4
Q

True or false: it is much easier to treat CINV than prevent it

A

false
much easier to prevent than treat

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5
Q

What are the types of CINV?

A

acute:
-occurs within 24h of tx
-serotonin dependent: use 5HT3 receptor antagonists
delayed:
-occurs 24-120h post-tx
-substance P dependent: use NK1 receptor antagonists
anticipatory:
-occurs as a conditioned response due to past negative experiences
-lorazepam
breakthrough:
-occurs despite appropriate prophylactic anti-emetics and/or requires rescue agents

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6
Q

What percentage of patients will experience delayed phase CINV if their acute phase is controlled?

A

24%
-while those who do not have control in the acute phase have been shown to experience CINV up to 80% of the time

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7
Q

What are the major factors predicting risk for acute CINV?

A

treatment related:
-intrinsic property of drug (emetogenecity)
-dose, route, rate of infusion
-repeated cycles
patient related:
-lower alcohol consumption, younger age, female
-history of motion sickness
-history of NV during pregnancy
-poor control with prior chemotherapy

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8
Q

What are the major factors predicting risk for delayed CINV?

A

treatment related:
-not well characterized with many chemotherapeutic agents
patient related:
-low alcohol consumption, younger age, female
-history of motion sickness
-poor control of acute CINV

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9
Q

What are the antiemetics used in CINV?

A

5-HT3 antagonists
NK1 antagonists
corticosteroids
olanzapine
dopamine antagonists
benzodiazepines
marijuana derivatives

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10
Q

What is the 4 drug backbone in the acute setting for high emetic risk regimens?

A

5-HT3 antagonists
NK1 antagonists
corticosteroids
olanzapine

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11
Q

What are the 5HT-3 antagonists?

A

1st generation:
-ondansetron
-dolasetron
-granisetron
2nd generation:
-palonosetron

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12
Q

What is the MOA of 5-HT3 antagonists?

A

binds to receptors of serotonin
-located in CTZ and within the vagal afferent fibres from the upper GIT

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13
Q

Which 5-HT3 antagonist is the best?

A

equivalent safety and efficacy
-used interchangeably based on convenience, availability, and cost

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14
Q

What can improve the efficacy of 5-HT3 antagonists?

A

corticosteroid

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15
Q

What are the side effects of 5-HT3 antagonists?

A

most common:
-headache and constipation
high doses:
-QT interval prolongation

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16
Q

When are 5-HT3 antagonists effective for CINV?

A

effective in the first 24h post-chemo (acute phase) but not on days 2-5 post-chemo (delayed phase)

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17
Q

What is the difference between palonosetron and the 1st generation 5-HT3 antagonists?

A

longer half life (44h)
QT prolongation not described

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18
Q

True or false: ondansetron and palonosetron can be combined for delayed NV

A

false

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19
Q

What are the NK1 receptor antagonists?

A

aprepitant (oral)
fosaprepitant (IV)
Akynzeo (oral)
-netupitant with palonosetron

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20
Q

What is the MOA of NK1 receptor antagonists?

A

blocks binding of substance P at the NK1 receptor in the CNS

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21
Q

When are NK1 receptor antagonists given?

A

on day 1 prior to chemotherapy

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22
Q

What are the drug interactions of NK1 receptor antagonists?

A

3A4 and 2C9
dex requires 50% dose reduction

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23
Q

What are NK1 receptor antagonists synergistic with?

A

5HT3 antagonists and a steroid

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24
Q

What is the indication for Akynzeo?

A

prevention of acute and delayed NV associated with HEC
-or prevention of acute NV with MEC uncontrolled by 5HT3 antagonist alone

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25
What is the dual mode of action of Akynzeo?
palonosetron is a 5-HT3 receptor antagonist netupitant is a selective NK1 receptor antagonist
26
Describe Akynzeo dosing for HEC and cisplatin-based regimens.
day 1: -Akynzeo x 1 one hour prior to chemo + DEX 12 mg day 2-4: -DEX 8 mg
27
Describe Akynzeo dosing for AC and chemotherapy not considered to be highly emetogenic.
day 1: -Akynzeo x 1 one hour prior to chemo + DEX 12 mg day 2-4: -DEX not necessary
28
What are the side effects of Akynzeo?
in clinical trials, Akynzeo was generally well-tolerated -most common AE: HA, constipation, fatigue
29
What is the half-life of netupitant?
96 h
30
What is the use of corticosteroids in CINV?
prevention of acute and delayed CINV -used with 5HT3 antagonists and NK1 antagonists for high emetic risk group non-AC and AC based regimens; as well as carboplatin regimens
31
What is the MOA of corticosteroids in CINV?
MOA unclear -may affect PG activity in the brain
32
Which corticosteroid is of choice for CINV?
dexamethasone
33
What are the side effects of corticosteroids?
insomnia heartburn increased BG in diabetics
34
What is the treatment of choice for NV in patients receiving radiation to the brain?
dexamethasone -as it reduces cerebral edema
35
What is the dosing of dexamethasone for high risk CINV?
acute emesis: 20 mg once -12 mg if with Akynzeo delayed emesis: 8 mg BID x 3-4 days -8 mg daily if with Akynzeo
36
What is the MOA of olanzapine in CINV?
acts on several receptors -dopamine (D1, D2, D3, D4) -serotonin (5HT2A, 5HT2C, 5HT3, 5HT6) -catecholamines (a1) -acetylcholine (muscarinic) -histamine (H1)
37
What is the use of olanzapine in HEC and MEC protocols?
with a 5-HT3 antagonist and dexamethasone, with or without an NK1 antagonist
38
What are the uses of olanzapine in CINV?
very effective in preventing delayed nausea used for breakthrough NV
39
What are some side effects of olanzapine?
sedation weight gain *caution in elderly and T2DM*
40
What did the RCT studying olanzapine and metoclopramide in breakthrough NV find?
superiority for olanzapine over metoclopramide for breakthrough NV
41
What are examples of dopamine antagonists?
metoclopramide prochlorperazine haloperidol
42
What is the MOA of dopamine antagonists?
block dopamine receptors on the CTZ
43
What is the use of dopamine antagonists in CINV?
mild, moderate and HEC, often for breakthrough symptoms
44
What are the side effects of dopamine antagonists?
mild sedation dystonic reactions (esp with metoclopramide) restlessness diarrhea
45
Which benzodiazepine is most commonly used in CINV?
lorazepam
46
What is the use of benzodiazepines in CINV?
prevent anticipatory emesis used as anti-anxiety or sleeping aid reduce restlessness from DA antagonists
47
What might be seen with benzodiazepine use with numerous chemotherapy cycles?
efficacy may decrease
48
True or false: benzodiazepine are strong antiemetics
false relatively weak antiemetic; not often as a single agent
49
What are the MASCC emetic risk groups for IV agents?
high: risk in > 90% of pts moderate: risk in 30-90% of pts low: risk in 10-30% of pts minimal: risk in < 10% of pts
50
Which IV agents are high emetic risk?
anthracycline/cyclophosphamide carmustine chlormethine cisplatin
51
Which IV agents is moderate emetic risk?
carboplatin -AUC greater than or equal to 4 likely high risk
52
Provide a summary of acute NV.
high non-AC: -5HT3 + NK1 + DEX + OLZ high AC: -5HT3 + NK1 + DEX + OLZ moderate, carboplatin AUC >4: -5HT3 + NK1 + DEX *referring to day 1*
53
Provide a summary of delayed NV.
high non-AC: -OLZ + DEX high AC: -OLZ moderate, carboplatin > AUC 5: -no additional prophylaxis
54
Describe appropriate prevention of acute/delayed NV following non-AC chemo of high emetic risk.
acute phase: 4 drug regimen -5HT3 antagonist -NK1 antagonist -dexamethasone -olanzapine delayed phase: -dexamethasone + olanzapine on days 2-4 to prevent delayed NV
55
Describe appropriate prevention of acute/delayed NV following AC-based chemo of high emetic risk.
acute phase: 4 drug regimen -5HT3 antagonist -NK1 antagonist -dexamethasone -olanzapine delayed phase: -olanzapine on days 2-4 to prevent delayed NV
56
What is the recommended dose of olanzapine in CINV?
5 mg
57
Describe appropriate prevention of acute/delayed NV following carboplatin chemo of moderate risk.
acute phase: 3 drug regimen (AUC greater than or equal to 4) -5HT3 antagonist -NK1 antagonist -dexamethasone delayed phase: -no steroid (or other antiemetic) should be routinely administered after day 1 carboplatin administration
58
What does the available evidence suggest for breakthrough NV?
use of olanzapine if not previously used as prophylaxis -if prev used, increasing to 10 mg could be more effective
59
What are some commonly employed strategies for breakthrough NV?
move up to the next emetogenic level add one agent from a different class to the current regimen switch routes/dosage forms use of OLZ a good alternative
60
What is the best approach for prevention of anticipatory NV?
best possible control of acute and delayed NV -BZDs can reduce the occurrence of anticipatory NV -behavioral therapies may help treat
61
What are the risk factors for ANV?
age < 50 yrs NV after last chemo session post-tx NV described as mod/severe/intolerable feeling warm/hot all over after last chemo susceptible to motion sickness female high-state anxiety pt expectations of chemo nausea % of infusions followed by nausea post-chemo dizziness emetogenic potential hx of morning sickness during pregnancy
62
What is the dose of lorazepam for ANV?
0.5-1 mg po beginning on the night before tx and then repeated the next day 1-2 h before anticancer tx begins
63
What are some non-pharm options for CINV?
small, frequent meals bland foods (avoid acidic, spicy) calorically dense foods eating foods at room temp
64
What is the most common cancer in resource-rich and resource-poor settings?
breast cancer -lifetime probability of developing breast cancer is 1 in 6
65
How common is breast cancer?
incidence (females): -breast > lung > colorectal mortality (females): -lung > breast > colorectal
66
What are the risk factors for breast cancer?
female > male age (greater incidence with increasing age) genetics
67
What is an important determinant of improving survival with breast cancer?
early detection and intervention improves survival
68
How is the diagnosis of breast cancer confirmed?
biopsy
69
What is the prognosis of breast cancer related to?
extent of disease
70
What is taken into account when deciding to use adjuvant chemotherapy in breast cancer?
tumour histology expression of ER or PR receptors tumor stage and grade patient age high-risk features (ex: lymphovascular invasion)
71
Which chemotherapy regimen is mostly used for breast cancer?
doxorubicin and cyclophosphamide (AC) followed by paclitaxel -referred to as AC-T
72
What does breast cancer adjuvant therapy ideally improve?
disease free survival and overall survival
73
What is adjuvant breast cancer therapy often given in addition to?
surgery to reduce risk of recurrence
74
True or false: metastatic breast cancer is not curable
true
75
What are the goals of treatment for metastatic breast cancer?
prolong survival and improve QoL by reducing cancer-related sx -cytotoxic chemotherapy may be used to achieve these goals -pts with HER2+ dx should have HER2-directed agents

PHAR359 (28 decks)

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