PHRM 542 Oncology Supportive Care CINV

Define nausea

Subjective symptom

Perception that vomiting may occur

Define retching

Non-productive attempt to vomit

Precede or alternate with vomiting

Define vomiting

Objective symptom

Explosive expulsion of GI contents

Describe the central mechanism of chemotherapy induced nausea/vomiting (CINV)

Delayed phase

Substance P and NK1 receptors

NK1 receptor antagonists primarily working here

Describe the peripheral mechanism of CINV

Acute phase

Serotonin and 5HT3 (serotonin) receptors

Serotonin antagonists primarily working here

Define acute CINV

Occurring within first 24 hours of initiation of chemotherapy

Define delayed CINV

Occurring from 24 hours to several days (days 2-5) after chemotherapy

Define breakthrough CINV

Occurring despite appropriate prophylactic treatment

Define anticipatory CINV

Occurring before a treatment as a conditioned response to the occurrence of CINV in previous cycles

Define refractory CINV

Recurring in a subsequent cycles of therapy, excluding anticipatory CINV

What are patient-related risk factors for CINV?

Females > males (pregnancy-related nausea)

Young age

Low alcohol consumption

Anxiety

Fatigue

Anticipation of CINV

Prone to motion sickness

What are chemotherapy related risk factors for CINV?

Chemotherapy emetogenicity

Dose

Route

Infusion duration

Other drugs administered = multi-drug regimens, concomitant medications

Define minimal emetogenic potential

0 - < 10%

Define low emetogenic potential

10-30%

Define moderate emetogenic potential

> 30-90%

Define high emetogenic potential

> 90%

How long is the risk period for patients on highly emetogenic chemotherapy (HEC)?

4 days

How long is the risk period for patients on moderately emetogenic chemotherapy (MEC)?

3 days

How should antiemetic therapy be chosen for multi drug regimens?

Antiemetic therapy is based on the drug with the highest emetic risk

What is the MOA of NK-1 antagonists?

Inhibit neurokinin-1 receptor in CTZ and VC which mediates the emetogenic effects of Substance P

What type of N/V are NK-1 antagonists used for?

Delayed N/V

What is the MOA of serotonin antagonists?

Selective 5-HT3-receptor antagonist which blocks serotonin, both peripherally on vagal nerve terminals and centrally in the CTZ

What type of N/V are serotonin antagonists used for?

Acute AND delayed N/V

What type of N/V is dexamethasone used for?

Acute AND delayed N/V

When may dexamethasone require a reduced dose for CINV?

When used with most NK-1 inhibitors (except rolapitant)

What type of N/V is olanzapine used for?

Acute AND delayed N/V

Which NK-1 antagonist should be avoided in patients with a CrCl < 30 mL/min?

Netupitant

What is the FDA max single dose of ondansetron?

16 mg IV

Which serotonin receptor antagonist has limited efficacy for DELAYED nausea and less QT prolongation compared to other drugs in the class?

Palonosetron

When should dexamethasone be used with caution?

In uncontrolled diabetes = consider serotonin antagonists

How should breakthrough CINV be managed?

Optimal to add one agent from a different drug class to current regimen

Use agent NOT used for acute or delayed emesis prevention

Which medication should never be used alone as an antiemetic?

Lorazepam = use for anticipatory CINV/breakthrough only

Describe the treatment of anticipatory CINV

Behavioral therapies with systemic desensitization

Acupuncture/acupressure

Benzodiazepines

What is the place in therapy of NK-1 antagonists?

Used for the PREVENTION of CINV, NOT for treatment

Largest benefit seen in a delayed CINV setting