Management of Chemotherapy-Induced Nausea and Vomiting (CINV) PDF

Management of Chemotherapy- induced Nausea and Vomiting (CINV) Oncology Supportive Care- Sec. 3 Oncology Supportive Care OSC consists of : 1) Antiemetics 2) Pain Management 3) Chemotherapy- Induced Bone Marrow Suppression: Neutropenia Thrombocytopenia Anemia & fatigue 4) Chemo...

Management of Chemotherapy- induced Nausea and Vomiting (CINV) Oncology Supportive Care- Sec. 3 Oncology Supportive Care OSC consists of : 1) Antiemetics 2) Pain Management 3) Chemotherapy- Induced Bone Marrow Suppression: Neutropenia Thrombocytopenia Anemia & fatigue 4) Chemo Protectants 5) Oncologic Emergencies 6) Miscellaneous Antineoplastic Table of Content Contents that will be covered throughout this PowerPoint; Defintion of Nausea and vomiting; Definition of CINV and its Introduction on CINV types; Pathophysiology of N/V and Neurotransmittors involved in CINV Risk Assessment for CINV Risk factors related to CINV General Rules of Emesis Rules in the prevention and treatment of CINV control for cancer patients Primary Pharmacological Medications used for CINV management Groups Recommended treatment regimens by Recommended Algorithms NCCN/ASCO/MASC/ESMO Case Study Managing in a CINV in a High-risk patients 01 Introduction  Whereas, Nausea is described as an awareness of unpleasant discomfort that may or may not precede vomiting. nausea is accompanied by: Decreased gastric tone Decreased peristalsis 70-80% of patients who undergo chemotherapy expierence nause and vomiting Understanding CINV CINV is a common side effect of chemotherapy, affecting the gastrointestinal tract and CNS due to chemotherapy drugs. Impact CINV can severely impact patients’ quality of life, adherence to therapy, and overall outcomes. Incidence and Types of CINV Nausea and vomiting can occur at different times during cancer treatment Acute Delayed Anticipatory Occurs 0–24 hours Occurs more than Conditioned response- it after chemotherapy 24 hours after is more likely to occur in administration and chemotherapy patients whose previous commonly resolves administration post-chemotherapy within 24 hours nausea and vomiting was (intensity peaks not well controlled. after 5–6 hours) Incidence and Types of CINV Nausea and vomiting can be described based on how well antinausea medicines work against them: Breakthrough Emesis Refractory Emesis Occurs despite Occurs during treatment prophylactic treatment or cycles when antiemetic necessitates additional prophylaxis or rescue rescue medications therapy has failed in previous cycles.  Pathophysiology of Nausea and Vomiting A stimuli for nausea are processed through several major anatomic areas, each of which has various receptos associated with input to the medullary vomiting center. There are 4 important sources of vagal afferent input to the vomiting center: Chemoreceptor Trigger Zone (CTZ) Vestibular System Cerebral Cortex Visceral Stimuli (GIT) Pathophysiology of CINV Peripheral Mechanism Local generation of free radicals >>> localized exocytotic release of serotonin (5-HT) from the enterochromaffin cells >>> 5-HT interacts with 5-HT3 receptors on vagal afferent terminals in the bowel wall >>> stimulates vagal afferent fibers, which project to CTZ. This peripheral mechanism of emesis in intestinal tract is believed to be 5-HT3 receptor dominant and plays a key role in acute emesis. Pathophysiology of CINV Central Mechanism Afferent stimulation from the vagus >>> release of Substance P in the CTZ. This central mechanism of emesis is believed to be NK1 receptor dominant and plays an important role in delayed emesis. Antineoplastic agents may also induce emesis through a direct interaction with Vomiting center>>> D2 receptor.  02 Risk Assessment for CINV (1) Patient-related Risk Factors 1 2 3 4 Younger age (< Female sex History of History of N/V 50 years) Motion during sickness pregnancy 7 6 5 History of chronic Rapid metabolizers Poor control of alcoholism (+ve risk of certain 5-HT3 N/V in previous factor- decrease receptor chemotherapy incidence of emesis) antagonists cycles (2) Emetogenicity of Chemotherapy Agents Parentral Agents High Moderate >90 percent risk of emesis >30 to 90 percent risk of emesis Low Minimal 10-30 percent risk of 90% frequency of emesis) (30%-90% frequency of emesis) AC (combination defined as any Doxorubicin < 60 mg/m2 Doxorubicin (liposomal) chemotherapy regimen that Epirubicin ≤ 90 mg/m2 contains an anthracycline and Idarubicin cyclophosphamide) Daunorubicin Doxorubicin ≥ 60 mg/m2 Epirubicin > 90 mg/m2 Carboplatin AUC ≥ 4 Carboplatin AUC < 4 Methotrexate (50-250 mg/m2) Cisplatin Ifosfamide ≥ 2 g/m2/dose Ifosfamide < 2 g/m2/dose Paclitaxel Mechlorethamine Cytarabine > 200mg/m2 Cytarabine (low dose)100-200 mg Amifostine >300 mg/m2 Amifostine ≤300 mg/m2 Cyclophosphamide >1500 mg/m2 Cyclophosphamide ≤ 1500 mg/m2 (2) Emetogenicity of Chemotherapy Agents Oral Agents Moderate or high Minimal or low >30 percent risk of > antagonists Rolapitant (Varubi) Glucocorticoids Dexamethasone Atypical antipsychotics Olanzapine  Most Common Antiemetic Regimen A B C Moderate Mildly emetogenic Highly emetogenic emetogenic Dexamethasone OR An NK1R antagonist, a A 5-HT3 receptor 5-HT3 receptor 5-HT3 receptor antagonist antagonist OR antagonist, Dexameth and Dexamethasone Phenothiazine-(eg, asone and Olanzapine An NK1R antagonist prochlorperazine)  Antiemetics (1) Serotonin-3 Receptor Antagonists (1) Serotonin-3 Receptor Antagonists Mechanism of action (MOA): Block serotonin receptors Palonosetron is indicated to prevent acute CINV for peripherally in the gastrointestinal tract and centrally in highly emetogenic chemotherapy and acute and delayed the medulla CINV for moderately emetogenic chemotherapy. Dolasetron, granisetron, ondansetron, and palonosetron i. Half-life: About 40 hours (longer compared with other are considered equally efficacious at equivalent dosages serotonin antagonists) Dosage forms: Granisetron and ondansetron are available ii. Dosage: 0.25 mg intravenous push 30 minutes before in oral and parenteral forms (including an orally chemotherapy administration disintegrating tablet for ondansetron). Granisetron is also iii. An oral capsule form is available but only as a available in a transdermal patch as well as an extended- combination product with an NK1 antagonist release subcutaneous formulation. (netupitant/palonosetron). (2) NK1 Receptor Antagonists (2) NK1 Receptor Antagonists Aprepitant, aprepitant injectable emulsion, Aprepitant oral dosage: 125 mg on day 1, then 80 mg fosaprepitant, rolapitant; all must be used in on day 2 and 80 mg on day 3.// Intravenous aprepitant combination with a serotonin receptor antagonist and dosing is 130 mg on day 1 only for highly emetogenic dexamethasone >> acute and delayed N/V induced by chemotherapy and 100 mg on day 1 only for high emetogenic drugs. moderately emetogenic chemotherapy. MOA: Aprepitant is a selective high-affinity Fosaprepitant dosage (prodrug): 150 mg intravenously antagonist of human substance P/NK1. on day 1 only (parenteral formulation)  Antiemetics (3) NK1 /Serotonin-3 Receptor Antagonist (4) Corticosteroids MOA: Fixed combination of netupitant/fosnetupitant, a Dexamethasone >>> synergistic effect substance P/NK1 receptor antagonist, and palonosetron, a Given in combination as it’s very effective and potentiates 5-HT3 receptor antagonist indicated for the prevention of serotonin receptor antagonist acute and delayed N/V highly - moderately emetogenic Given orally or IV drugs Systemic glucocorticoids may be avoided in patients Netupitant/palonosetron dosage: 1 capsule once on day 1 receiving immune checkpoint inhibitors (ICIs) due to (capsule contains 300 mg of netupitant/ palonosetron 0.5 concerns that they might attenuate the benefit of ICI mg) immunotherapy, Fosnetupitant/palonosetron dosage: IV once on day 1 (contains 235 mg of fosnetupitant/palonosetron 0.25 mg) (5) Atypical Antipsychotic (6) Other Dopamine Antagonists Olanzapine Is a FDA approved drug to treat schizophrenia Benzodiazepines (lorazepam): MOA: Anterograde amnesia and bipolar disorder; dopamine antagonist helps prevent anticipatory N/V Off label use as an alternative agent for preventing N/V in Benzamide analogs (metoclopramide): MOA: Blockade of highly emetogenic regimens dopamine receptors in the chemoreceptor trigger zone; Used as an option for breakthrough N/V increasing (forward) gut motility; and antagonism of When Olanzapine was compared with aprepitant in highly peripheral serotonin receptors in the intestines. emetogenic chemotherapy regimens; same effect in Phenothiazines (prochlorperazine) and Butyrophenones Acute N/V, but Olanzapine is more effective in prevention (haloperidol): MOA: Block dopamine receptors in the of delayed chemoreceptor trigger zone NK1 Receptor Antagonist- D-Drug Interactions Dexamethasone: Fosaprepitant and aprepitant may increase area under the curve of dexamethasone. Decrease dosage by about 40% on day 2 or 3 if dexamethasone given orally (not necessary if given intravenously because of first-pass metabolism). If patients do not receive an NK1R antagonist, the dexamethasone dose should be adjusted to 20 mg on day 1 and 16 mg daily on days 2 to 4. Oral contraceptives: May reduce the effectiveness of oral contraceptives. Would recommend another form of birth control for women of childbearing age when taking with aprepitant/ fosaprepitant Warfarin: May decrease international normalized ratio (INR) (clinically significant). After receiving fosaprepitant or aprepitant, patients should have their INR checked within 7–10 days 05 Medication Algorithm Case Study A 60-year-old woman was recently given a diagnosis of advanced non–small cell lung cancer. She will begin treatment with cisplatin 100 mg/m2 plus vinorelbine 30 mg/m2. 1. Which is the most appropriate antiemetic regimen for preventing acute emesis? A. Aprepitant plus palonosetron plus dexamethasone. B. Aprepitant plus prochlorperazine plus dexamethasone. C. Aprepitant plus granisetron plus ondansetron. D. Lorazepam plus ondansetron plus metoclopramide Case Study A 60-year-old woman was recently given a diagnosis of advanced non–small cell lung cancer. She will begin treatment with cisplatin 100 mg/m2 plus vinorelbine 30 mg/m2. 2. If the patient has anticipatory nausea and vomiting with her next cycle, which regimen would be most appropriate? A. Aprepitant plus palonosetron plus dexamethasone plus lorazepam. B. Aprepitant plus prochlorperazine plus dexamethasone. C. Aprepitant plus granisetron plus metoclopramide. D. Aprepitant plus ondansetron plus dexamethasone plus lorazepam Thanks Do you have any questions?