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Chemotherapy-induced nausea and vomiting (CINV)

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Detailed notes on CINV.

  • CINV
  • chemotherapy
  • nausea
  • vomiting
  • antiemetics

By Dr. Ayesha Fatima

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  1. Slide 1. CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV) Presented by Dr. AYESHA FATIMA Pharm D Assistant Professor Dept of Pharmacy Practice
  2. Slide 2. NAUSEA ∙ Nausea is a subjective, unpleasant sensation often felt in the back of the throat and epigastrium, commonly described as an urge to vomit. ∙ It is not directly observable and originates from a complex interplay between the gut and the central nervous system, often involving neurotransmitters like serotonin (5-HT3), dopamine (D2), and substance P (neurokinin-1, NK1). VOMITING (EMESIS) ∙ Vomiting is a forceful expulsion of stomach contents through the mouth, mediated by the vomiting center in the brainstem. ∙ Unlike nausea, it is an observable physical act, involving coordinated muscular contractions of the abdomen, diaphragm, and stomach.
  3. Slide 3. EMETOGENICITY ∙ Emetogenicity refers to the capacity or tendency of a drug—particularly a chemotherapeutic agent—to cause nausea and/or vomiting. ∙ It is a critical concept in oncology because nausea and vomiting (together known as CINV: Chemotherapy-Induced Nausea and Vomiting) are among the most distressing side effects for patients undergoing cancer treatment. ∙ Emetogenic potential of chemotherapeutic agents, based on the modified Hesketh scale (as used by ASCO and NCCN). ∙ This classification helps guide the use of appropriate antiemetic prophylaxis depending on the risk of nausea and vomiting.
  4. Slide 4. Category Definition Examples of Agents Recommended Regimen Highly Emetogenic Agents that cause nausea and/or vomiting in >90% of patients Cisplatin Cyclophosphamide (>1500 mg/m²)- Dacarbazine-Carmustine NK₁ antagonist + 5-HT₃ antagonist + Dexamethasone Moderately Emetogenic Agents that cause CINV in 30% to 90% of patients - Doxorubicin- Cyclophosphamide (≤1500 mg/m²)- Oxaliplatin- Irinotecan 5-HT₃ antagonist + Dexamethasone (± NK₁ antagonist) Low Emetogenic Agents associated with 10% to 30% incidence of CINV - Etoposide- Paclitaxel- Docetaxel- Fluorouracil Dexamethasone or 5-HT₃ antagonist alone Minimally Emetogenic Agents that cause CINV in <10% of patients - Vincristine- Vinblastine- Bleomycin- Methotrexate (low dose) PRN antiemetics (e.g., metoclopramide, prochlorperazine)
  5. Slide 5. CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV) ∙ “CINV” is a broad term used to describe the many types of nausea and vomiting that can occur in patients with cancer. ∙ CINV refers to nausea and/or vomiting resulting from chemotherapy treatment. ∙ It is one of the most distressing and feared side effects of cancer therapy. ∙ CINV can significantly affect a patient’s quality of life, nutritional status, and willingness to continue treatment. Epidemiology ∙ Despite the introduction of new antiemetics, 30%–60% of patients undergoing chemotherapy still experience nausea or vomiting. ∙ Vomiting has decreased in prevalence due to improved pharmacological management, but nausea remains highly prevalent, often reported as the first or second most severe chemotherapy side effect.
  6. Slide 6. Risk Factors for (CINV) Patient Specific 1. Female sex 2. History of motion sickness 3. H/o pregnancy-induced emesis (morning sickness) 4. Younger age 5. Low alcohol consumption 6. High anxiety level Treatment Specific 1. Highly emetogenic chemotherapy agents 2. Dose and schedule of chemotherapy 3. Site of radiation (in RINV) 4. Surgical factors (in PONV)
  7. Slide 7. Type of CINV Timing of Onset Incidence Description & Key Features Acute CINV Within 24 hours of chemotherapy Very common Begins within minutes to hours after administration; peaks around 5–6 hours; subsides in 24h. Late-Acute CINV Between 12–24 hours after chemotherapy Subtype of acute Considered part of acute CINV, but onset occurs in the later part of the 24- hour window. Delayed CINV More than 24 hours post-chemotherapy (up to 5–7 days) 50–80% (especially with cisplatin, doxorubicin) Often underreported and poorly controlled; occurs after patient leaves treatment site. Types of CINV
  8. Slide 8. Anticipatory CINV Before chemotherapy (conditioned response) 20–30% by 4th cycle; 8–20% per cycle Triggered by sights, smells, or thoughts of chemo; due to prior negative experiences; behavioral therapy is most effective. Breakthrough CINV At any time, despite prophylactic antiemetics Varies; requires rescue medication Occurs when standard prevention fails; requires additional antiemetic therapy. Refractory CINV In subsequent cycles, when prior control was inadequate <10% of patients CINV that continues even after previous prophylaxis failed; difficult to manage.
  9. Slide 9. Pathophysiology
  10. Slide 11. Pharmacologic Management of Chemotherapy-Induced Nausea and Vomiting (CINV) • Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect of cancer treatment. Effective management involves a combination of antiemetic agents targeting different pathways involved in emesis. • The most effective regimen for CINV prevention is a combination of 5-HT₃ antagonists, NK₁ antagonists, and dexamethasone, tailored to the emetogenicity of the chemotherapy.
  11. Slide 12. Classification of Antiemetic Agents Antiemetics used for CINV are classified based on their mechanism of action: 1. 5 -HT₃ Receptor Antagonists (Serotonin Antagonists) : e.g. Ondansetron , Granisetron , Dolasetron, Palonosetron 2. NK₁ Receptor Antagonists (Neurokinin-1 Antagonists) : e.g. Aprepitant, Fosaprepitant, Rolapitant, Netupitant 3. Corticosteroids : e.g. Dexamethasone , Methylprednisolone 4. Dopamine Receptor Antagonists a. Substituted Benzamides : e.g., Metoclopramide b. Butyrophenones : e.g., Haloperidol, Droperidol c. Phenothiazines : e.g., Prochlorperazine 5. Atypical Antipsychotics e.g., Olanzapine 6. Cannabinoids e.g., Dronabinol, Nabilone 7. Benzodiazepines e.g., Lorazepam, Alprazolam 8. Antihistamines e.g., Cyclizine, Diphenhydramine
  12. Slide 13. Triple Therapy for CINV • Triple therapy is the gold-standard antiemetic regimen used to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC) (e.g., cisplatin, carmustine). • Triple Therapy Recommended for: • Highly emetogenic chemo (HEC) (e.g., cisplatin, carmustine, cyclophosphamide ≥1,500 mg/m ² ). • Some moderately emetogenic regimens (MEC) if patient has risk factors (e.g., prior CINV, female, young age). • It combines three key drug classes to block multiple pathways involved in CINV:
  13. Slide 14. Dosing Schedule Day 1 (Chemo Day): • Palonosetron (0.25 mg IV) OR Ondansetron (8 – 16 mg oral/IV). • Fosaprepitant (150 mg IV) OR Aprepitant (125 mg oral). • Dexamethasone (12 mg oral/IV; reduced to 8 mg if combined with aprepitant). Days 2 – 4 (Delayed Phase): • Aprepitant (80 mg oral, days 2 – 3). • Dexamethasone (8 mg oral, days 2 – 4). Drug Class Example Agents Role in CINV Prevention 5-HT₃ Receptor Antagonist Palonosetron (preferred), Ondansetron, Granisetron Blocks acute- phase nausea/vomiting (first 24 hrs) by inhibiting serotonin in the gut and brain. NK₁ Receptor Antagonist Aprepitant, Fosaprepitant, Rolapitant Prevents delayed- phase CINV (days 2–5) by blocking substance P in the brain. Cortico steroid Dexamethasone Enhances efficacy of other drugs and reduces inflammation.
  14. Slide 15. 5-HT₃ Receptor Antagonists : ∙ Block serotonin (5-HT₃) receptors in the gut (vagal afferents) and the chemoreceptor trigger zone (CTZ). ∙ First-line for acute CINV (first 24 hours post-chemotherapy). ∙ Most effective when combined with dexamethasone. ∙ Given 30–60 min before chemotherapy. ∙ Adverse Effects: Headache, constipation, dizziness., QTc prolongation (caution in cardiac patients)., Mild transaminase elevation.
  15. Slide 16. NK₁ Receptor Antagonists ∙ Block substance P (a neurokinin) in the brainstem and gut. ∙ Aprepitant (oral, approved in 2003), Fosaprepitant (IV prodrug of aprepitant, approved in 2008), Rolapitant (long-acting, single-dose option) ∙ Highly effective for both acute and delayed CINV, especially with highly emetogenic chemotherapy (HEC). ∙ Used in combination with 5-HT₃ antagonists + dexamethasone. ∙ Given 30–60 min before chemotherapy. ∙ Adverse Effects: Fatigue, hiccups, diarrhea, elevated liver enzymes. ∙ Drug Interactions: o CYP3A4 inhibitor → increases dexamethasone levels o Weak CYP2C9 inducer → may decrease warfarin efficacy.
  16. Slide 17. Corticosteroids ∙ modulate prostaglandins and serotonin. ∙ Key component in both acute and delayed CINV prevention. ∙ Enhances the effects of 5-HT₃ and NK₁ antagonists. ∙ Adverse Effects: Insomnia, hyperglycemia, mood changes, peptic ulcers. Atypical Antipsychotics (Olanzapine) ∙ Blocks multiple receptors (5-HT₂, D₂, H₁). ∙ Effective for both acute and delayed CINV. ∙ Used as an adjunct in highly emetogenic regimens. ∙ Adverse Effects: Sedation, weight gain, hyperglycemia. Cannabinoids (Dronabinol, Nabilone) ∙ Act on CB1 receptors in the CNS. ∙ Use: Refractory CINV (third-line). ∙ Adverse Effects: Euphoria, dizziness, hypotension, dependence.
  17. Slide 18. Dopamine Receptor Antagonists i. Substituted Benzamides (Metoclopramide) • D₂ and mild 5-HT₃ blockade. • Use: Rescue therapy for breakthrough CINV. • Adverse Effects: Extrapyramidal symptoms (EPS), neuroleptic malignant syndrome (NMS). ii. Butyrophenones (Haloperidol, Droperidol) • Strong D₂ antagonism. • Use: Less common due to sedation and EPS risk. iii. Phenothiazines (Prochlorperazine, Promethazine) ∙ D₂ and histamine blockade. ∙ Use: Low-emetogenic chemotherapy or adjunct therapy. ∙ Adverse Effects: Sedation, hypotension, EPS.
  18. Slide 19. Emetogenic Risk Recommended Regimen Preferred Agents High 3-drug: 5-HT3 RA + NK1 RA + Dexamethasone Palonosetron preferred; Moderate 2-drug: 5-HT3 RA + Dexamethasone Palonosetron preferred Low Dexamethasone alone or alternatives Alternatives: Metoclopramide, Prochlorperazine Minimal No prophylaxis recommended – CINV Prophylaxis
  19. Slide 20. Radiation Risk Recommended Regimen Preferred Agents High (e.g., TBI) 5-HT3 RA ± Dexamethasone Granisetron, Ondansetron Moderate (e.g., upper abdomen) 5-HT3 RA ± Dexamethasone (fractions 1–5) Same as above Low (e.g., head/neck) Rescue treatment only 5-HT3 RA or Metoclopramide, Prochlorperazine Minimal (e.g., breast) No routine prophylaxis – Combination of chemo + radiation Based on chemo emetogenicity (or radiation if higher risk) – Radiation-Induced Nausea and Vomiting (RINV)

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