Chemotherapy Induced Nausea and Vomiting (CINV) Flashcards
What are the consequences of not controlling chemo N/V? (5)
- Medical complications: electrolyte imbalances, dehydration
- Poor quality of life
- Poor adherence
- Dose reductions; treatment delays
- Poor outcomes
What are the goals of controlling chemo N/V? (2)
- No emesis
- No (or mild) nausea
What are some general ways in which chemo N/V can be controlled? (5)
- No one drug or strategy will work for all patients
- Reassess efficacy prior to each cycle
- For maximal benefit, initiate anti-emetics prior to chemotherapy
- Much easier to prevent than to treat
- Scheduled anti-emetics versus PRNs
What are the 4 types of CINV?
- Acute
- Delayed
- Anticipatory
- Breakthrough
What is acute CINV? What neurotransmitter is involved? (2)
- Occurs within 24 hours of treatment
- Serotonin dependent – use 5HT3 receptor antagonists
What is delayed CINV? What neurotransmitter is involved? (2)
- Occurs 24 to 120 hours post treatment
- Substance P dependent – use NK1 receptor antagonists
What is anticipatory CINV? (1)
Occurs as a conditioned response due to past negative experience (occurs prior to chemo) (lorazepam)
What is breakthrough CINV? (1)
Occurs despite appropriate prophylactic anti-emetics and/or requires rescue agents
Should know the key point (mechanism) in how acute CINV actually occurs
The acute phase emesis is largely initiated by serotonin from enterochromaffin cells located in the intestinal mucosa. Serotonin binds to 5-HT3 receptors located on vagal afferent nerves in the intestinal wall, which send signals via the chemotherapy trigger zone in the area postrema to the vomiting centre in the medulla
What are 2 major factors predicting risk for acute/delayed CINV?
- Treatment related
- Patient related
What are treatment related factors for predicting acute CINV? (3)
- Intrinsic property of drug - emetogenecity
- Dose, route, rate of infusion
- Repeated cycles
What are patient related factors for predicting acute CINV? (2+3)
- Patient characteristics
- Lower alcohol consumption, younger age, female
- History of motion sickness
- History of n/v during pregnancy - Poor control with prior chemotherapy
What are treatment related factors for predicting delayed CINV? (1)
Not well characterized with many chemotherapeutic agents
What are patient related factors for predicting delayed CINV? (2+2)
- Patient characteristics
- Low alcohol consumption, younger age, female
- History of motion sickness - Poor control of acute CINV
What is the 4 drug backbone (acute setting) for high emetic risk regimens? (antiemetics)
- 5-HT3 antagonist
- NK1 antagonist
- Corticosteroids
- Olanzapine
What are the 3 first generation serotonin receptor antagonists (anti-emetic)
- Ondansetron
- Dolasetron
- Granisetron
When are first generation serotonin receptor antagonists most effective (anti-emetics)?
These agents have been shown to be effective in the first 24 hours postchemotherapy (acute phase), but not on days 2 to 5 postchemotherapy (delayed phase)
What is the second generation serotonin receptor antagonist drug?
Palonosetron
What are 2 neurokinin 1 (NK-1) receptor antagonist drugs?
- Fosaprepitant (IV)
- Akynzeo - is NK-1 combined with palonosetron
What 2 drugs are present in Akynzeo?
Netupitant/palonosetron
What are 2 indications of Akynzeo?
- The prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy (HEC)
- The prevention of acute nausea and vomiting associated with moderately emetogenic chemotherapy (MEC) that is uncontrolled by a 5-HT3 receptor antagonist alone
What is the MOA of Akynzeo? (3)
- Akynzeo®, a fixed-dose combination of netupitant and palonosetron, has a dual mode of action targeting both the 5-HT3 and NK1 receptor neuropathways
- Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for 5-HT3 receptors
- Netupitant is a selective NK1 receptor antagonist that inhibits substance P-mediated responses, as shown in in vivo and in vitro studies
Carboplatin AUC >_ is when we consider it to be high
4
Need to know the highly emetogenic chemotherapy (HEC), including cisplatin-based regimens anti-emetic treatment, with dosing, days 1-4
Day 1:
- Akynzeo 1 capsule, ~1 hour prior to the start of each chemotherapy cycle
- Dexamethasone 12mg
Day 2:
- DEX 8mg
Day 3:
- DEX 8mg
Day 4:
- DEX 8mg
Need to know the anthracycline-cyclophosphamide (AC) and chemotherapy not being considered to be highly emetogenic - also includes carboplatin (AUC 4+) anti-emetic regimens, with dosing for days 1-4
Day 1:
- Akynzeo 1 capsule, ~1 hour prior to the start of each chemotherapy cycle
- DEX 12mg
Days 2-4 NO DEX REQUIRED POST
What are the half-lives of palonosetron and netupitant (akynzeo)
Palonosetron = 44 hours
Netupitant = 96 hours
What is the corticosteroid of choice for prevention of acute and delayed CINV?
Dexamethasone is often the treatment of choice for N/V in pts receiving radiation to the brain, as it also reduces cerebral edema
When in CINV is olanzapine useful? (2)
- Very effective in preventing delayed nausea
- Used for breakthrough N/V
What are 2 side effects of olanzapine?
- Sedation
- Weight gain
Who should be cautioned in using olanzapine? (2)
- Elderly
- Type 2 diabetics (hyperglycemia)
Olanzapine or metoclopramide for CINV, which is preferred?
Olanzapine is drug of choice over metoclopramide
What is the MOA of dopamine antagonists for anti-emesis?
Block dopamine receptors on the CTZ
- Used in mild, moderate and HEC, often for breakthrough symptoms
What is the most common benzo used for anti-emesis?
Lorazepam
When is lorazepam used in CINV?
What is the MOA? (5)
- Prevent anticipatory emesis
- Used as anti-anxiety or sleeping aid
- Reduce restlessness from dopamine antagonists
- Efficacy may decrease with numerous cycles
- Relatively weak antiemetic; not often as a single agent
What is high emetic risk classified as (IV agent)?
Risk in >90% of pts
What is moderate emetic risk classified as (IV agent)?
Risk in 30% to 90% of pts
What is low emetic risk classified as (IV agent)?
Risk in 10% to 30% of pts
What is minimal emetic risk classified as (IV agent)?
Risk in <10% of pts
What are 3 high risk emetic IV chemo agents?
- AC
- Cisplatin
- Carboplatin AUC 4+
Should know the Day 1 MASCC acute nausea and vomiting high non-AC antiemetic regimen
- Akynzeo (5-HT3 and NK1)
- Dex
- Olanzapine
Should know the Day 2-4 MASCC acute nausea and vomiting high non-AC antiemetic regimen
Olanzapine + Dex
Should know the Day 1 MASCC acute nausea and vomiting high AC antiemetic regimen
- Akynzeo (5-HT3 and NK1)
- Dex
- Olanzapine
Should know the Day 2-4 MASCC acute nausea and vomiting high AC antiemetic regimen
Olanzapine
Should know the Day 1 MASCC acute nausea and vomiting high carboplatin (>4 AUC) antiemetic regimen
- Akynzeo (5-HT3 and NK1)
- Dex
Should know the Day 2-4 MASCC acute nausea and vomiting high carboplatin (>4 AUC) antiemetic regimen
Nothing
What is the olanzapine dose for basically all the anti-emetic regimens?
5mg PO daily
If olanzapine 5mg was initially used, but not enough, increasing to __mg could be more effective
10
What are some common strategies to help with breakthrough nausea and vomiting? (4)
- ‘Move up to the next emetogenic level’ example: if at moderate, treat at high
- Add one agent from a different class to the current regimen
- Switch routes/dosage forms: oral, IV, ODT, suppository, liquid
- Use of olanzapine is a good alternative
What is the best possible treatment for anticipatory N/V? (3)
- The best approach for the prevention of anticipatory nausea and vomiting is the best possible control of acute and delayed nausea and vomiting
- Behavioral therapies (progressive muscle relaxation training, in particular), systematic desensitization, and hypnosis may be used to treat anticipatory nausea and vomiting
- Benzodiazepines can reduce the occurrence of anticipatory nausea and vomiting.
What are some risk factors for anticipatory N/V? (12)
- Age younger than 50 years
- N and V after the last chemotherapy session
- Post-treatment nausea/vomiting described as moderate, severe, or intolerable
- Feeling warm or hot all over after the last chemotherapy session
- Susceptibility to motion sickness
- Female
- High-state anxiety
- Patient expectations of chemotherapy-related nausea before beginning treatment
- Percentage of chemotherapy infusions followed by nausea
- Post-chemotherapy dizziness
- Emetogenic potential of various chemotherapeutic agents. Patients receiving drugs with a moderate to high potential for post-treatment N and V are more likely to develop ANV
- History of morning sickness during pregnancy
What do you NEED to know about using lorazepam for anticipatory N/V (when to use)?
Must be used the night before treatment and 1-2 hours before chemo begins
How should we assess patients when it comes to CINV? (5)
- Assess each new patient prior to treatment, following each cycle as well as any change in treatment
- Every patients experience with nausea and vomiting is unique
- History
- Goals – adherence and compliance
- Diet
What are some non-pharm options to help with CINV? (4)
- Small, frequent meals
- Bland foods (avoid acidic, spicy)
- Calorically dense foods
- Eating foods at room temperature
Lifetime risk for breast cancer is?
1 out of 8 people
What are some risk factors for breast cancer?
Genetics
- 2 or more first degree relatives with premenopausal breast cancer
- 5 -10% of patients have hereditary form
- genetic mutations BRCA-1 and BRCA-2 lifetime risk 36 - 85%
- few other disorders associated with increased risk
For most breast cancer patients in whom chemotherapy is recommended, we mostly use: (3)
Doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), otherwise referred to as AC-T
What is adjuvant therapy? (7)
- Targets microscopic metastatic disease
- Should be effective on minimal foci of disease
- Unsure of efficacy in particular patient
- Ideally improves disease free survival (DFS) and overall survival (OS)
- Treatment given in addition to surgery to reduce risk of recurrence
- May include radiation therapy, chemotherapy, hormonal therapy, or targeted therapy
- Often a combination of these different modalities
True or False? Metastatic breast cancer is curable
False - not curable
What are the goals of treatment for metastatic breast cancer?
The goals of treatment of metastatic breast cancer are to prolong survival and improve quality of life by reducing cancer-related symptoms
