Oncology 6 Flashcards
What are the consequences of not controlling CINV?
medical complications
-elyte imbalances, dehydration
poor QoL
poor adherence
dose reductions; tx delays
poor outcomes
What is the goal with treatment of CINV?
no emesis
no (or mild) nausea
How are the goals of CINV achieved?
reassess efficacy prior to each cycle
for maximal benefit, initiate anti-emetics prior to chemotherapy
scheduled anti-emetics vs prn
True or false: it is much easier to treat CINV than prevent it
false
much easier to prevent than treat
What are the types of CINV?
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
What percentage of patients will experience delayed phase CINV if their acute phase is controlled?
24%
-while those who do not have control in the acute phase have been shown to experience CINV up to 80% of the time
What are the major factors predicting risk for acute CINV?
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
What are the major factors predicting risk for delayed CINV?
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
What are the antiemetics used in CINV?
5-HT3 antagonists
NK1 antagonists
corticosteroids
olanzapine
dopamine antagonists
benzodiazepines
marijuana derivatives
What is the 4 drug backbone in the acute setting for high emetic risk regimens?
5-HT3 antagonists
NK1 antagonists
corticosteroids
olanzapine
What are the 5HT-3 antagonists?
1st generation:
-ondansetron
-dolasetron
-granisetron
2nd generation:
-palonosetron
What is the MOA of 5-HT3 antagonists?
binds to receptors of serotonin
-located in CTZ and within the vagal afferent fibres from the upper GIT
Which 5-HT3 antagonist is the best?
equivalent safety and efficacy
-used interchangeably based on convenience, availability, and cost
What can improve the efficacy of 5-HT3 antagonists?
corticosteroid
What are the side effects of 5-HT3 antagonists?
most common:
-headache and constipation
high doses:
-QT interval prolongation
When are 5-HT3 antagonists effective for CINV?
effective in the first 24h post-chemo (acute phase) but not on days 2-5 post-chemo (delayed phase)
What is the difference between palonsetron and the 1st generation 5-HT3 antagonists?
longer half life (44h)
QT prolongation not described
True or false: ondansetron and palonosetron can be combined for delayed NV
false
What are the NK1 receptor antagonists?
aprepitant (oral)
fosaprepitant (IV)
Akynzeo (oral)
-netupitant with palonosetron
What is the MOA of NK1 receptor antagonists?
blocks binding of substance P at the NK1 receptor in the CNS
When are NK1 receptor antagonists given?
on day 1 prior to chemotherapy
What are the drug interactions of NK1 receptor antagonists?
3A4 and 2C9
dex requires 50% dose reduction
What are NK1 receptor antagonists synergistic with?
5HT3 antagonists and a steroid
What is the indication for Akynzeo?
prevention of acute and delayed NV associated with HEC
-or prevention of acute NV with MEC uncontrolled by 5HT3 antagonist alone
What is the dual mode of action of Akynzeo?
palonosetron is a 5-HT3 receptor antagonist
netupitant is a selective NK1 receptor antagonist
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
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
What are the side effects of Akynzeo?
in clinical trials, Akynzeo was generally well-tolerated
-most common AE: HA, constipation, fatigue
What is the half-life of netupitant?
96 h
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
What is the MOA of corticosteroids in CINV?
MOA unclear
-may effect PG synthesis
Which corticosteroid is of choice for CINV?
dexamethasone
What are the side effects of corticosteroids?
insomnia
heartburn
increased BG in diabetics
What is the treatment of choice for NV in patients receiving radiation to the brain?
dexamethasone
-as it reduces cerebral edema
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
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)
What is the use of olanzapine in HEC and MEC protocols?
with a 5-HT3 antagonist and dexamethasone, with or without an NK1 antagonist
What are the uses of olanzapine in CINV?
very effective in preventing delayed nausea
used for breakthrough NV
What are some side effects of olanzapine?
sedation
weight gain
caution in elderly and T2DM
What did the RCT studying olanzapine and metoclopramide in breakthrough NV find?
superiority for olanzapine over metoclopramide for breakthrough NV
What are examples of dopamine antagonists?
metoclopramide
prochlorperazine
haloperidol
What is the MOA of dopamine antagonists?
block dopamine receptors on the CTZ
What is the use of dopamine antagonists in CINV?
mild, moderate and HEC, often for breakthrough symptoms
What are the side effects of dopamine antagonists?
mild sedation
dystonic reactions (esp with metoclopramide)
restlessness
diarrhea
Which benzodiazepine is most commonly used in CINV?
lorazepam
What is the use of benzodiazepines in CINV?
prevent anticipatory emesis
used as anti-anxiety or sleeping aid
reduce restlessness from DA antagonists
What might be seen with benzodiazepine use with numerous chemotherapy cycles?
efficacy may decrease
True or false: benzodiazepine are strong antiemetics
false
relatively weak antiemetic; not often as a single agent
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
Which IV agents are high emetic risk?
anthracycline/cyclophosphamide
carmustine
chlormethine
cisplatin
Which IV agents is moderate emetic risk?
carboplatin
-AUC greater than or equal to 4 likely high risk
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
Provide a summary of delayed NV.
high non-AC:
-OLZ + DEX
high AC:
-OLZ
moderate, carboplatin > AUC 5:
-no additional prophylaxis
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
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
What is the recommended dose of olanzapine in CINV?
5 mg
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
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
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
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
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
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
What are some non-pharm options for CINV?
small, frequent meals
bland foods (avoid acidic, spicy)
calorically dense foods
eating foods at room temp
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
How common is breast cancer?
incidence (females):
-breast > lung > colorectal
mortality (females):
-lung > breast > colorectal
What are the risk factors for breast cancer?
female > male
age (greater incidence with increasing age)
genetics
What is an important determinant of improving survival with breast cancer?
early detection and intervention improves survival
How is the diagnosis of breast cancer confirmed?
biopsy
What is the prognosis of breast cancer related to?
extent of disease
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)
Which chemotherapy regimen is mostly used for breast cancer?
doxorubicin and cyclophosphamide (AC) followed by paclitaxel
-referred to as AC-T
What does breast cancer adjuvant therapy ideally improve?
disease free survival and overall survival
What is adjuvant breast cancer therapy often given in addition to?
surgery to reduce risk of recurrence
True or false: metastatic breast cancer is not curable
true
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
