Chemotherapy-Induced Nausea and Vomiting (CINV) Prophylaxis and Management

Vocabulary practice flashcards covering chemotherapy-induced nausea and vomiting (CINV) pathophysiology, emetic risk stratification, pharmacotherapy classes, adverse effects, and NCCN guideline regimens.

Chemotherapy-Induced Nausea and Vomiting (CINV)

One of the most common side effects of chemotherapy, involving nausea and emesis that can lead to decreased oral intake of fluids and calories.

Primary Goal of CINV Management

Prevention of CINV, which is critical to successful clinical management and avoiding severe complications.

Chemoreceptor Trigger Zone (CRTZ)

An area located outside the blood-brain barrier in the medulla oblongata that constitutes the central pathway responsible for delayed emesis.

Peripheral Pathway of CINV

The pathway involving vagal afferent nerves in the gastrointestinal tract that stimulates acute emesis.

Acute CINV

Nausea and vomiting occurring within $24$ hours of chemotherapy administration (peaking around $5\text{--}6$ hours), stimulated via the peripheral vagal afferent pathway.

Delayed CINV

Nausea and vomiting developing $1$ to $5$ days after chemotherapy, mediated by the central pathway (CRTZ) and typically triggered by alkylating agents.

Breakthrough CINV

Nausea and vomiting that occurs despite the use of current preventative antiemetics.

Anticipatory CINV

A conditioned emetic response occurring before anticancer treatment begins, triggered by anticipation from prior CINV episodes.

Refractory CINV

Nausea and vomiting occurring during subsequent chemotherapy cycles after appropriate antiemetic prophylaxis and rescue treatments have failed.

High Emetic Risk Category

Chemotherapy agents causing emesis in $>90\%$ of patients, including: cisplatin, dacarbazine, nitrogen mustards, procarbazine, carboplatin AUC $\ge 4$, cyclophosphamide ($>1.5\,\text{g/m}^2$), and the AC regimen.

Moderate Emetic Risk Category

Chemotherapy agents causing emesis in $30\%-90\%$ of patients, including alemtuzumab, anthracyclines, carboplatin AUC $< 4$, cyclophosphamide ($\le 1.5\,\text{g/m}^2$), ifosfamide, irinotecan, and oxaliplatin.

Low Emetic Risk Category

Chemotherapy agents causing emesis in $10\%-30\%$ of patients, including etoposide, 5-fluorouracil, gemcitabine, methotrexate, paclitaxel, taxanes, and topotecan.

Minimal Emetic Risk Category

Chemotherapy agents causing emesis in $<10\%$ of patients, including bevacizumab, bleomycin, fludarabine, rituximab, and vinca alkaloids.

AC Regimen

A combination chemotherapy regimen consisting of doxorubicin plus cyclophosphamide classified as having high emetic risk ($>90\%$ of patients).

Major Risk Factors for CINV

Patient-specific characteristics increasing CINV risk: female sex, age $>50$, history of low prior chronic alcohol intake, and history or severity of prior CINV.

Minor Risk Factors for CINV

Secondary patient-specific factors that increase susceptibility to CINV: history of motion sickness, history of emesis during pregnancy, and anxiety.

5-HT3 Receptor Antagonists

A class of antiemetics that block serotonin receptors in both the chemoreceptor trigger zone and the gastrointestinal tract, primarily targeting the acute CINV pathway.

Common Side effects —→ Fatigue, malaise, GI disturbances (cinstpiation, diarrhea, and pain), QTc prolongation (SERIOUS), caution in patients with high CV risk

Dolasetron

A 5-HT3 receptor antagonist that is no longer commercially available due to its risk of causing QTc prolongation.

Palonosetron

A second-generation 5-HT3 receptor antagonist typically recommended because of its higher binding affinity and longer half-life; also formulated in combination with netupitant.

NK-1 Receptor Antagonists

A drug class that blocks substance P from binding neurokinin-1 receptors, playing a pivotal role in the prevention of delayed CINV.

Common Side effects: Diarrhea, fatigue, Neutropenia

Substance P

A neurotransmitter involved in the mediation of CINV that binds to neurokinin-1 (NK-1) receptors to trigger emetic pathways.

Aprepitant

An oral NK-1 receptor antagonist administered once daily for $3\text{--}4$ days that crosses the blood-brain barrier, inhibits CYP3A4, and induces CYP2C9.

Fosaprepitant

An intravenous NK-1 receptor antagonist administered as a one-time IV dose that inhibits the CYP3A4 pathway.

Rolapitant

An NK-1 receptor antagonist that does not inhibit CYP3A4, avoiding drug-drug interactions and requiring no corticosteroid dose reduction.

Olanzapine

An atypical antipsychotic blocking dopamine, serotonin, and histamine receptors, supported at approximately $5\,\text{mg}$ twice daily for CINV prevention and breakthrough therapy.

Dexamethasone

A corticosteroid utilized in both the prevention and treatment of CINV that works synergistically to enhance the effectiveness of other antiemetic agents.

Dopamine Antagonists

A drug class including metoclopramide, promethazine, and prochlorperazine utilized primarily to treat breakthrough CINV.

Irreversible Extrapyramidal Symptoms (EPS)

Serious neurological adverse effects associated with dopamine antagonists, including akathisia, dystonia, tardive dyskinesia, and drug-induced parkinsonism.

Cannabinoids (Dronabinol and Nabilone)

Antiemetic agents reserved for refractory CINV in patients who fail conventional treatments; their use is restricted by Schedule 1 status and complex pharmacology.

Benzodiazepines in CINV

A drug class utilized specifically for the prevention and management of anticipatory CINV.

Triple-Drug Approach

A prophylactic antiemetic regimen for moderate-to-high emetic risk chemotherapy combining a 5-HT3 receptor antagonist, an NK-1 receptor antagonist, and dexamethasone.

Day 1 IV Prophylaxis for HIGH Emetic Risk

5-HT3 receptor antagonist + dexamethasone + NK-1 receptor antagonist.

Day 1 IV Prophylaxis for MODERATE Emetic Risk

5-HT3 receptor antagonist + dexamethasone

Day 1 IV Prophylaxis for LOW Emetic Risk AND minimal risk

LOW - Choose ONE:

1. 5-HT3 receptor antagonist

2. Dexamethasone

3. Metoclopramide // Prochlorperazine

MINIMAL:

1. No Routine Prophylaxis recommended

Administered AFTER-Day 1 IV Prophylaxis for HIGH Emetic Risk

1. Dexamethasone

   1. duration Days $2\text{--}4$ after receiving high emetic risk chemotherapy

Administered AFTER-Day 1 IV Prophylaxis for MODERATE Emetic Risk

1. Dexamethasone OR

2. 5-HT3 receptor antagonist

   1. duration on days 2-3

Non-Pharmacological CINV Interventions

Complementary approaches with demonstrated positive results, including:

• acupuncture /acupressure

• ginger

• dietary alterations

• relaxation techniques

• hypnosis

• guided imagery

• behavioral therapy.