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Chemo-Induced Nausea and Vomiting (CINV)

Chemo-Induced Nausea and Vomiting (CINV). Elshami M. Elamin, MD Medical oncologist Central Cancer Care Center www.cccancer.com Wichita, KS - USA. Causes of N/V in cancer patients. Chemo RT Bowel obstruction Brain mets Electrolytes imbalance Hypercalcemia, Hyponatremia,

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Chemo-Induced Nausea and Vomiting (CINV)

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  1. Chemo-Induced Nausea and Vomiting (CINV) Elshami M. Elamin, MD Medical oncologist Central Cancer Care Center www.cccancer.com Wichita, KS - USA

  2. Causes of N/V in cancer patients • Chemo • RT • Bowel obstruction • Brain mets • Electrolytes imbalance • Hypercalcemia, • Hyponatremia, • Hyperglycemia • Uremia • Opiates • Gastroparesis (Vincrestine) • Psycophysiologic: • Anxiety • Anticipating N/V

  3. Pathophysiology of Emesis

  4. CINV Acute Onset: minutes-hrs Resolves: first 24 hrs Delayed Platinum, Cytoxan, Doxo Onset: >24 hrs May last for 7 days Anticipatory Breakthrough/Refractory Always remember: Dyspepsia may mimic Nausea It is easier to prevent N/V than to treat it

  5. ANTI-EMETICS

  6. Emesis neuroreceptors • Serotonin: 5-HydroxyTtryptamine (5-HT3) • Dopamine • Acetylcholine • Corticosteroid • Histamine • Cannabinoid • Opiate • Neurokinin-1 (NK-1)

  7. Dopamine antagonists 1-Metoclopramide (Reglan) and Domperidone (Motilium) Sensitize tissues to acetylcholine Stimulate upper GIT motility Facilitate gastric emptying Increase esophageal peristalsis Increase LES pressure Antagonize central and peripheral dopamine receptors Block dopamine receptors in chemoreceptor trigger zone in CNS 2- Haloperidol

  8. Anxiolytics/Anti-psychotics Benzodiazepine (Lorazepam) May give the night before and after chemo Phenothiazine: Prochlorperazine (Compazine): Anti-dopaminergic effect Blocking dopamine receptors Blocking vagus nerve in GIT

  9. Watch for Dystonic reaction Prochlorperazine Metoclopramide Domperidone 1- Diphenhydramine OR 2- Benztropine

  10. Serotonin (5-HT3) antagonists Dolasetron (Anzemet) Risk of cardiac arrhythmia with IV (IV is NOT recommended) Granisetron (Kytril) Patch = 3-5 days PO Ondansetron (Zofran) Palonosetron (Aloxi) 100-fold higher binding affinity to 5-HT3 receptors More effective at decreasing nausea 40 hrs half-life: Good option for 3 days chemo Repeat and higher dose 0.75 mg is likely safe *Acute emesis: Prior to first dose of mod-highly emetogenic chemo

  11. Neurokinin-1 Antagonist Aprepitant (Emend) Selectively blocks binding of substance P at NK-1 receptor in CNS Not an alternative to any anti-emetic regimen Augments anti-emetic effect of 5-HT3 antagonists and Dexa for acute and delayed emesis *Acute/Delayed emesis: Along with 5-HT3 + Dexa Prior to multi-day highly emetogenic chemo

  12. Neurokinin-1 Antagonist Aprepitant (Emend) Dosages + 5-HT3 + Dexa: Aprepitant 125mg po d1, 80 mg po d2-3 Fosaprepitant 115 mg IV d1, aprepitant 80 mg po d2-3 Fosaprepitant 150 mg IV d1 only With 150 dose use Dexa 8 mg po bid d3-4

  13. Be Aware of Aprepitant Drug interaction (more with PO than IV) • Do NOT give with: • 1- Pimozide (antipsychotic) • 2- Terfenadine (Seldane) • 3- Astemizole (Hismanal) • 4- Cisapride (propulsid)

  14. Steroids Dexamethasone Improve efficacy of 5-HT3 antagonists With Aloxi for moderate risk: 8 mg d1 enough No need on d 2-3 Do Not use if chemo include steroids e.g. ESHAP Contra-indicated with: IL-2 IFN *Acute emesis: PO/IV Prior to mod-highly emetogenic chemo *Delayed emesis: Days 2-3

  15. Steroids Dexamethasone Always keep in mind its side effects *Hyerglycemia *HTN *Fluid retension *PU *Osteoporosis

  16. Miscellaneous Antipsychotic : Olanzapine (zyprexa) Cannabinol: Dronabinol (marinol) 5-10 mg OR Nabilone 1-2 mg Anti-histamine: Promethazine (phenergan) H2-Blocher or PPI

  17. Which anti-emetic you should chose for your patient? • Anti-emetic regimens should be chosen based on: • Chemo drugs and their sequence in the regimen • Acute and delayed emesis may overlap • Goal of chemo: Palliative vs Adj/curative • Patient specific risk factors • Smoker • Alcoholic: less N/V • Gender, Age (more CINV in young female) • Hx of N/V or motion sickness • Prior experience with anti-emetics

  18. Delayed Emesis • 5-HT3 antagonists (except palonosetron) are less effective for delayed emesis • A meta-analysis of randomized controlled trials: • Adding 5-HT3 antagonist to Dexa did NOT improve antiemetic effect of Dexa for delayed emesis • Another study: • 5-HT3 antagonists (except Aloxi, not studied) NOT more effective than prochlorperazine for delayed emesis • A Canadian meta-analysis: • Ondansteron alone did help for delayed emesis • Not cost-effective to use 5-HT3 antagonists on d 2-4

  19. Categories of Emetogenic Chemotherapy • High emetic risk • Moderate emetic risk • Low emetic risk • Minimal emetic risk

  20. High Emetic Risk IV Chemo(> 90% frequency of emesis) • AC / EC • Carmustine > 250 mg/m • Cisplatin > 50 mg/m • Cytoxan > 1,500 mg/m • Dacarbazine • Doxo > 60 mg/m • Epirubicin > 90 mg/m • Ifex > 10 g/m • Mechlorethamine • Streptozocin 3 days of anti-emetic

  21. Potent ematogenic drugs: • Platinum • Doxorubicin • Cytoxan • Dacarbazine

  22. Lorazepam 5-HT3 Antagoist Aprepitant Dexa PPI/H2-blocker Dopamine antagonist

  23. High Emetic Risk IV ChemoAcute and Delayed Emesis Prevention Premedication: • Serotonin (5-HT3) antagonist • Dolasetron (Anzemet) 100 mg po (Not IV) OR • Granisetron (Kytril) 2 mg po bid OR 0.01mg/kg (max 1mg) IV OR transdermal patch applied 24-48hr before chemo (last for 7 d) OR • Ondansetron 16-24 mg po OR 8-24 mg (max 32mg/d) IV OR • Palonosetron (Aloxi) 0.25mg IV

  24. High Emetic Risk IV ChemoAcute and Delayed Emesis Prevention + Steroid: • Dexa 12mg po or IV d1, 8mg po d2-4 (with emend 125 po or 115mg IV d1) OR • Dexa 12mg po or IV d1, 8 mg po d2, 8 mg po bid d3-4 (with fosaaprepitant 150mg IV d1) + Neuokinin 1 Antagonist: • Aprepitant 125mg po d1, 80 mg po d2-3 OR • Fosaprepitant 115 mg IV d1, aprepitant 80 mg po d2-3 OR • Fosaprepitant 150 mg IV d1 only +/- Loraxepam +/- H2 Blocher or PPI

  25. Moderate Emtic Risk agents (30-90% frequency of emesis) • Aldesleukin > 12-15 mIU/m • Amifostine • Arsenic Trioxide • Azacitidine • Bendamustine • Busulfan • Carbo • Carmustine < 250 mg/m • Cisplatin < 50 mg/m • Cytoxan < 1,500 mg/m • Doxo < 60 mg/m • Epirubicin < 90mg/m • Idarubicin • Ifex < 10 g/m • CPT-11 • Melphalan • MTX • Oxali • Temozolomide 2 days of anti-emetic

  26. Moderate Emetic Risk IV Chemo: Emesis Prevention • Premedication: • Day 1: Serotonin (5-HT3) antagonist: • Dolasetron 100 mg po (Not IV) OR • Granisetron (Kytril) 2 mg po bid OR 0.01mg/kg (max 1mg) IV OR transdermal patch applied 24-48hr before chemo (last for 7 d) OR • Ondansetron 16-24 mg po OR 8-24 mg (max 32mg/d) IV OR • Palonosetron (Aloxi) 0.25mg IV

  27. Moderate Emetic Risk IV Chemo: Emesis Prevention • Day 1: + Steroid: Dexa 12 mg +/- Neurokinin 1 antagonist: • Aprepitant 125 mg po OR • Fosaprepitant 115 mg IV d1 +/- Lorazepam PRN +/- H2 Blocker or PPI

  28. Moderate Emetic Risk IV Chemo: Emesis Prevention • Day 2-3: • Serotonin (5-HT3) antagonist monotherapy: • Dolasetron 100 mg po (Not IV) OR • Granisetron (Kytril) 1-2 mg po qd or 1 mg bid OR 0.01mg/kg (max 1mg) IV OR • Ondansetron 8 mg po bid OR 16 mg qd OR 8 mg (max 32mg/d) IV OR OR • Steroid momontherapy: Dexa 8 mg qd OR • Neurokinin 1 antagonist +/- steroid (if emend used on d1): • Aprepitant 80 mg po +/- Dexa qd +/- Lorazepam PRN +/- H2 Blocker or PPI

  29. Amifostine <300 mg Cabazitaxel Cytarab 100-200 mg/m Doce Doxil VP-16 5-FU Gemzar MTX 50-250 mg/m Mitomycin Mitoxantrone Taxol Alimta Pentostatin Topotecan Ixabepilone Low Emetic Risk IV Chemo: (10-30% frequency of emesis)

  30. Low Emetic Risk IV Chemo: Emesis Prevention • Dexa 12 mg OR • Metoclopramide 10-40 mg PRN • Prochlorperazine 10 mg PRN • Monitor for dystonic reaction • Use Diphenhydramine or Benztropine (cogentin) • +/- Lorazepam PRN • H2 Blocker or PPI

  31. Alemtuzumab (Campath) Asparaginase Bleomycin Bortezomib (velcade) Cetuximab Avastin Cytarabine <100 Fudara IFN < 5mIU/m MTX < 50mg/m Panitumumab Rituxan Torisel Herceptin Vinblastine Vincristine Vinorelbine Minimal Emetic Risk IV Chemo (<10% frequency of emesis)

  32. Minimal Emetic Risk IV Chemo: Emesis Prevention • No routine prophylaxis

  33. Busulfan (>4 mg/d) Cytoxan >100 mg/m/d Estramustine VP-16 Lomustine (CeeNU) Procarbazine Temozolomide > 75mg/m/d Moderate to High Emetic Risk Oral Chemo

  34. High to Moderate Emetic Risk Oral Chemo: Emesis Prevention • Serotonin 5-HT3 antagonist: • Dolasetron 100 mg po (Not IV) OR • Granisetron (Kytril) 2 mg po qd or 1 mg bid OR • Ondansetron 16-24 mg po qd +/- Lorazepam PRN +/- H2 Blocker or PPI

  35. Busulfan < 4 mg/d Xeloda Chloambucil Cytoxan < 100 mg/m/d Dasatinib Tarceva/Iressa Everolimus Fludara Hydrea Imatinib Lapatinib Revlimid Melphalan Mercaptopurine MTX Nilotinib Sorafenib Sunitinib Temozolomide < 75 mg/m/d Thalidomide Topotecan Tretioin Minimal to Low emetic Risk Oral Chemo

  36. Low to minimal Emetic Risk Oral Chemo: Emesis Prevention • Metoclopramide 10-40 mg PRN • Prochlorperazine 10 mg PRN • Monitor for dystonic reaction • Use Diphenhydramine or Benztropine (cogentin) • Haloperidol 1-2 mg po PRN +/- Lorazepam PRN +/- H2 Blocker or PPI • 5-HT3 antagonist if N/V persist N/V PRN

  37. Radiation-Induced N/V • RT-upper abd/localized sites • Pretreatment daily: • Granisetron 2 mg qd OR • Ondansetron 8 mg bid • +/- Dexa 4 mg qd • TBI: • Pretreatment: • Granisetron 2 mg qd OR • Ondansetron 8 mg bid-tid • +/- Dexa 4 mg qd • ChemoRT: • CIN/V protocol

  38. Breakthrough Treatment for CIN/V First Step: Add one agent from a different drug class PRN • Antipsychotic : • Olanzapine (zyprexa) 2.5-5 mg po bid • Caution: elderly, DM • Benzodiazepine: • Lorazepam 0.5-2 mg • Cannabinol: • Dronabinol 5-10 mg OR Nabilone 1-2 mg • Dopamine antagonists: • Metoclopromide , Domperidone, Haloperidol • Phenothiazine: Prochlorperazine OR Promethazine • Serotonin 5-HT3 antagonists • Dexa

  39. Breakthrough Treatment for CIN/V Continue agent on Schedule Not PRN N/V controlled Second step: Agents from different drug class PRN Consider change antiemetics to higher level for next cycle N/V Not controlled Re-eval, adjust dose and or new drug

  40. Breakthrough CINV • The most difficult to treat • Consider routine (around the clock) rather than PRN • Rectal or IV rather than PO • Multiple, alternating agents and perhaps routes • Do not forget: • Hydration • Electrolytes • Brain mets • GI tumors

  41. It is not always medication to do it … • It is not always doctors and nurses to do it … • It is most of the time you as patient to do it … • It could be simple and easy ….

  42. Anticipatory N/V

  43. Anticipatory N/V • Seen in 20% of patients • Decreasing • Prevention: • Optimal anti-emetic with each cycle • Acupuncture • Alprazolam 0.5-2 mg po tid beginning night before Or • Lorazepam 0.5-2 mg po night before and am

  44. Non-Medical measures • Eating small frequent meals • Choice of food • Easy on stomach • Eating food at room temperature Dietary consult

  45. Behavioral therapy • Relaxation/systematic desensitization • Hypnosis with guided imagery • Music therapy • Spiritual

  46. THANKS 48

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