Dr. Johnston Heme.Onc. Exam II Study Guide PDF

Embedded file printout Risk Factors for CINV Age: younger age, higher risk Gender: females \> males Negative alcohol/tobacco history Prior history of nausea and vomiting Pregnancy Motion sickness Previous experience with chemotherapy Chemotherapy factors Emetogenic (vomiting) potential of...

Embedded file printout Risk Factors for CINV Age: younger age, higher risk Gender: females \> males Negative alcohol/tobacco history Prior history of nausea and vomiting Pregnancy Motion sickness Previous experience with chemotherapy Chemotherapy factors Emetogenic (vomiting) potential of chemotherapy Dose relationship: higher dose, higher risk Combination chemotherapy Multiday therapies Bolus \> infusional: higher peak level with bolus Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Drugs Used Primarily to Prevent CINV Glucocorticoid corticosteroid: dexamethasone (Decadron) Multi-receptor antagonist (atypical antipsychotic): olanzapine (Zyprexa)\* Benzodiazdepine: lorazepam (Ativan) \*alpha-I, dopamine, histamine H-1, muscarinic, and serotonin type 2 (5-HT2) Embedded file printout Drugs Used Primarily to Prevent CINV Serotonin (5-HT3) receptor antagonists: ondansetron (Zofran) granisetron (Kytril, Sancuso) dolasetron (Anzemet) palonosetron (Aloxi) Neurokininl (NKI) receptor antagonists: aprepitant/fosaprepitant (Emend) netupitant/fosnetupitant (in Akyneo) rolapitant (Varubi) Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Key agent\  Embedded file printout Drugs Used to Primarily to Treat CINV Dopamine (D2) receptor antagonists: prochlorperazine (Compazine) haloperidol (Haldol) droperidol (Inapsine) metoclopramide (Reglan) trimethobenzamide (Tigan) Ink Drawings Ink Drawings  Embedded file printout Drugs Used Primarily to Treat CINV Cannabinoids: dronabinol (Marinol, Syndros) nabilone (Cesamet) cannabidiol (CBD) cannabis (marijuana) Ginger Ink Drawings Ink Drawings Ink Drawings  Embedded file printout \*Antiemetics to Prevent CINV: HighEmetic Risk Antineoplastics Common high-risk (\>90% risk of N/V) regimens include cisplatin or the combination of doxorubicin and cyclophosphamide (AC) 4 drug regimen before chemotherapy on day 1 that includes NKI antagonist + 5-HT3 antagonist + dexamethasone + olanzapine e Dexamethasone and olanzapine on days 2-4 after chemotherapy except when AC chemotherapy given, then olanzapine only days 2-4 to prevent delayed CINV Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout \*Antiemetics for Low Emetic Risk Antineoplastics Low-risk (10-30% frequency of N/V) include both IV and oral chemotherapy and many oral targeted agents Offer 1 drug before chemotherapy on day 1, either 5-HT3 antagonist or dexamethasone 8 mg Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Example of application of risk for CINV Patient with leukemia receiving cytarabine 100 mg/m2 daily IV continuous infusion on days 1-7 plus daunorubicin 60 mg/m2 IV bolus on days 1-3 (7+3 regimen) Cytarabine low dose is considered to be low risk Daunorubicin is considered to be moderate risk Emetogenic risk of this regimen = moderate; 3 drug regimen (ondansetron, aprepitant, dexamethasone) before daunorubicin at least days 1-3 Antiemetics may be decreased on days 4-7: either dexamethasone (dose may be reduced from 12 mg to 4 mg) or ondansetron. Ink Drawings Ink Drawings 2 Ink Drawings Ink Drawings Ink Drawings  Embedded file printout \*Prevention of CINV when Chemotherapy is given with a Checkpoint Inhibitor (Cl) e Example: Cisplatin-based doublet chemotherapy with pembrolizumab (Keytruda) for non-small cell lung cancer Cisplatin-based therapy has high emetic potential Glucocorticoids may block the immune effects of Cls and are commonly used to treat serious adverse effects of of Cls Current clinical trial evidence demonstrates effectiveness of chemo + Cl with or without dexamethasone BOTTOM LINE: Standard 4-drug regimen with dexamethasone should be used when highly emetic chemo is given with Cl Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Case 1 --- Chemotherapy-Induced N&V SD is a 55 year-old woman is scheduled to start her first cycle of chemotherapy with cisplatin 75 mg/m2 and vinorelbine for NSCLC What is this patient\'s risk for CINV? Cisplatin is high risk, vinorelbine is minimal risk, regimen is high risk. What antiemetic therapy, if any, should this patient receive? NKI antagonist + 5-HT3 antagonist + dexamethasone + olanzapine before then 5-HT3 and dexamethasone for 3-4 days after (ASCO) What would you add if the patient has nausea and vomiting BEFORE she receives her chemotherapy? Behavioral therapy and/or lorazepam Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Refractory CINV Add agents from different antiemetic classes, especially olanzapine to achieve control of N&V e Prevent and treat dehydration; treat electrolyte imbalances Review and add additional agents to CINV regimen before next cycle Consider changing antineoplastic regimen to decrease emetic potential Investigate non-antineoplastic agent causes of N&V May need to delay or stop antineoplastic therapy Ink Drawings  Embedded file printout Diarrhea Manifestation of chemo toxicity to lower Gl tract Uncontrolled diarrhea results in dehydration and electrolyte imbalances Increased hospital admissions Increased risk of local and systemic organism invasion (C.diff) May be sign of typhlitis (inflammation of the cecum in neutropenic patient) Drugs associated with increased risk of chemo-induced diarrhea Irinotecan\*, Ipilimumab\*, 5-FIuorouraciI Methotrexate, Capecitabine, Gemcitabine, Topotecan, Cytarabine, High-dose IL-2, EGFR inhibitors \*Dose-limiting toxicity: requires dose decrease, holding 1 or more doses, or stopping drug Note that several drugs are antimetabolites and 2 are topoisomerase I inhibitors; most are used to treat Gl cancers Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout ---Drug-Specific Diarrhea Tanagemen : Irinotecan (Camptosar) First 24 hours (cholinergic) Consider premedication with atropine 0.25-1 mg SC or IV Atropine up to 24 hours after irinotecan if diarrhea 24 hours or more after irinotecan High-dose loperamide (Imodium): 4 mg then 2 mg every 2 hours (24 mg/day); may give 4 mg every 4 hours at night Add diphenoxylate/atropine (Lomotil) 1-2 tablets every 6-8 hours if diarrhea poorly controlled at 12-24 hours After 24 hours, octreotide 100-150 mcg SC every 8 hours if uncontrolled or severe diarrhea; IV fluids; consider oral fluoroquinolone for prophylaxis Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout ---Drug-Specific Diarrhea Tanagemen : Checkpoint Inhibitors (except Ipilimumab) Severity grades 1-4 Grade 1 treatment Non-pharmacologic supportive care, may consider antidiarrheals May add mesalamine Continue checkpoint inhibitor if diarrhea improves Grade 2 or greater Hold checkpoint inhibitor Colonoscopy Corticosteroids Add infliximab (Remicade) or vedolizumab (Entyvio) depending on response to corticosteroids or severity of colitis Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings (prednisone) IF corticosteroids do not help  Embedded file printout Diarrhea: Neutropenic NO antimotility agents (loperamide or diphenoxylate/atropine (Lomotil) e Decrease fluid in stool by giving bulking agents or fiber agents (Benefiber, Fibercon, Fiberlax) TID May use bismuth subsalicylate (Pepto Bismol) 30 ml or 2 tablets every 6 hours prn in addition to fiber e Check for C diff and treat if present If C diff negative, then may begin octreotide 150 mcg IV q8h with max dose of 300 mcg if fiber agents are not working Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Constipation  Embedded file printout Treatment of Constipation Osmotic laxatives: Lactulose PEG 3350 (Miralax) Glycerin suppositories Magnesium salts (including milk of magnesia, magnesium citrate) Stimulant laxatives: Senna (Senokot) Bisacodyl (Dulcolax) Rectal laxatives (enemas/suppositories) Contraindicated in patients with neutropenia or thrombocytopenia Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Opioid-lnduced Constipation Therapeutic options for patients who fail maximum laxative therapy: Peripherally acting mu opioid receptor antagonists Methylnaltrexone (Relistor), SC injection\* or oral Naloxegol (Movantik) Naldemedine (Symproic) Type 2 chloride channel activator Lubiprostone (Amitiza)\* \*FDA-approved for opioid-induced constipation in patients with cancer receiving opioid therapy Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Constipation Management Case A 60 year-old patient receiving oral treatment for chronic leukemia develops constipation. His white blood cell, red blood cell, and platelet counts are low. A review of his medication list reveals that he is not taking any opioid analgesics or drugs with strong anticholinergic activity. Which of the following might be used to manage his constipation at this time, choose all that apply? 1. 2. 3. 4. 5. Bisacodyl suppository Increase fluid intake Start Methylnaltrexone (Relistor) Exercise as tolerated Add Miralax Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings  Embedded file printout Anorexia and Cachexia Mirtazapine (Remeron): antidepressant dose (15 mg- 30 mg daily) Cyproheptadine (Periactin): serotonin antagonist, antihistamine, more commonly used in children Metoclopramide (Reglan) if anorexia/cachexia due to delayed gastric emptying Glucocorticoids Ink Drawings Ink Drawings Ink Drawings Ink Drawings Ink Drawings