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Chemotherapy Induced Nausea Vomiting and Cancer Cachexia · PDF file 2012. 1. 19. · Chemotherapy Induced Nausea Vomiting and Cancer Cachexia Management: Pharmacist Perspectives

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  • Chemotherapy Induced Nausea Vomiting

    and Cancer Cachexia Management:

    Pharmacist Perspectives

    Suthan Chanthawong B. Pharm, Grad Dip in Pharmacotherapy

    Specialized Residency in Internal Medicine

    Faculty of Pharmaceutical Sciences, Khon Kaen University

    Advanced Pharmacotherapeutics I, 2012

    Oncology Section

  • CINV: Objective

     Pathophysiology of chemotherapy induced nausea and vomiting (CINV)

     Categories of CINV

     Pharmacologic agents indicated for CINV

     Current guidelines for CINV

     American Society of Clinical Oncology (ASCO)

    guideline: 2011 edition

    2

  •  Occurs in up to 80% of patients receiving CMT1

     In a study of 151 cancer patients from 10 community

    oncology centers who were scheduled for their first

    cycle of a new CMT regimen, 67% experienced either

    acute or delayed CINV during their first CMT cycle.2

     Delayed CINV was more common than acute CINV

    (59% vs 36%), although many patients experienced

    both types

     Anticipatory CINV occurs in 18–57%3

    1. Nevidjon B, Chaudry R. Supportive Oncology. 2010;8:1-10. 2. Cohen L et al. Support Care Cancer. 2007;15:497-503. 3.

    National Comprehensive Cancer Network. Antiemesis. Clinical Practice Guidelines in Oncology. 2010;2.2010.

    CINV prevalence

    3

  •  Nausea (Subjective quality)

     Awareness of the urge to vomit

     Retching: Non productive attempt to vomit

     Vomiting: Forceful expulsion of GI contents

     Intractable nausea

     Nausea and vomiting not adequately controlled after multiple antiemetics are used in series and combinations

     Anticipatory nausea

     Nausea and vomiting occurring as a result of a conditioned response from previous treatment

    Definitions of Nausea and Vomiting

    4

  •  Medical complications

     Electrolyte imbalances

     Dehydration

     Quality of life

     Impact daily functioning

     Compliance with chemotherapy

    Consequences of CINV

    5

  •  Evaluate the most likely etiology of the

    patient’s nausea and vomiting

     Use pathophysiology knowledge to determine

    the likely mechanism and involved receptors

     Choose appropriate therapy to target these

    receptors

    Treatment Approach

    6

  •  Acute: Within 24 hours of chemotherapy

     Delayed: Occurs > 24 hours after chemotherapy

     Anticipatory: Prior to chemotherapy

     Breakthrough: While receiving prophylactic antiemetics

     Refractory: Not responsive to therapy

    Classification of CINV

    7

  • CINV: Classification

    Anticipatory Acute Delayed

    Chemo

    16 - 24 hours 25 - 120 hours

    Breakthrough

    Refractory/Intractable

    8

  • Common Causes in Cancer Patients

    Nausea/ Vomiting

    Diseases

    Patient

    Treatment

    9

  •  Age men

     History of light alcohol use

     History of vomiting with prior exposure to chemotherapeutic agents

     Other risks

     History of motion sickness

     History of nausea or vomiting during pregnancy

     History of anxiety

    Patient-Specific Risk Factors for CINV

    ASHP. Am J Health Syst Pharm. 1999:56:729-764; Balfour and Goa. Drugs. 1997:54:273-298. 10

  •  Constipation

     Liver metastases

     Malignant bowel obstruction

     External compression of stomach or intestines by tumor

     Primary or metastatic brain

     Leptomeningeal disease

     Pain medications

    Common Causes in Cancer Patients

    11

  • Pathophysiology

    Adapted from JAMA 2007;298(10):1196-1207

    Chemoreceptor

    Trigger Zone Vomiting

    Center

    Cortex Vestibular System

    Peripheral

    Pathways

    Vagus and

    splanchnic

    nerves

    Intracerebral

    projections Vestibular nuclei

    projections

    Mechanical stretch

    GI mucosal injury

    Local toxins

    Drugs

    Metabolic products

    Bacterial toxins

    Motion

    Labyrinth disorders

    Sensory input

    Anxiety

    Increased ICP

    D2 5HT3

    NK1

    5HT3

    Chemo-

    receptors

    ACh

    H1

    ACh

    H1 5HT3

    12

  • Neurotransmitter Involvement

    13

    5-HT3 Other factors

    Acute

    Delayed

  • Chemotherapy-Induced Emesis:

    Key Treatment Milestones

    Palonosetron July, 2003 Aprepitant, March 2003

    14

  •  Serotonin Antagonists

     Corticosteroids

     NK1 Receptor Antagonist (i.e. Aprepitant)

     Dopamine antagonists

     Metoclopramide

     Phenothiazines (i.e. Prochloroperazine)

     Butyrophenones (i.e. Haloperidol)

     Benzodiazepines

     Cannabinoids (i.e. Marinol®)

    Classes of Antiemetic Agents

    15

  • ASCO Guideline

     Current guidelines for CINV

     American Society of Clinical Oncology (ASCO)

    guideline: 2011 edition

    16

  • Guideline Methodology: Systematic Review

     A systematic review provided preliminary literature for consideration:

    Agency for Healthcare Research and Quality (AHRQ)-

    funded Oregon Evidence-Based Practice Center

     An ASCO Update Committee considered pertinent literature through

    February 2010:

    MEDLINE

    Cochrane Collaboration Library

    ASCO Annual Meetings

    Multinational Association for Supportive Care in

    Cancer (MASCC) Meetings

    17

  • Categories for Antiemetics in Oncology

    Chemotherapy-Induced Nausea and Vomiting

    (CINV)

     Emetic risk of chemotherapy

     Combination chemotherapy

     Anticipatory nausea and vomiting

     Complementary therapy

     Adjunctive therapy

     Anticipatory CINV

    18

  • Categories for Antiemetics in Oncology

    CINV (cont’d)

     Special populations

     High Dose Chemotherapy

     Multi-day chemotherapy

     Pediatric Populations

    Radiation-Induced Nausea and Vomiting (RINV)

     Emetic risk by radiation site

     Combined chemotherapy and radiation therapy

    19

  • CHEMOTHERAPY-INDUCED

    NAUSEA AND VOMITING

    20

  • Emetic Risk Categories*

     Four emetic risk categories:

    High (>90%)

    Moderate (30%-90%)

    Low (10%-30%)

    Minimal (

  • 2011 Emetic Risk Categories of

    Single Agents Antineoplastics

    Emetic Risk Antineoplastic Agents Administered Intravenously

    High Moderate Low Minimal

    Carmustine

    Cisplatin

    Cyclophosphamide

    >1500 mg/m2

    Dacarbazine

    Dactinomycin

    Mechlorethamine

    Streptozotocin

    Azacitidine

    Alemtuzumab

    Bendamustine

    Carboplatin

    Clofarabine

    Cyclophosphamide

    1000

    mg/m2

    Daunorubicin*

    Doxorubicin*

    Epirubicin*

    Idarubicin*

    Ifosfamide

    Irinotecan

    Oxaliplatin

    Fluorouracil

    Bortezomib

    Cabazitaxel

    Catumaxomab

    Cytarabine

  • Recommendation by Risk Category, HEC

     2011 Recommendation:

     Three drug combination of

     NK1 antagonist,

     5-HT3 receptor antagonist, and

     Dexamethasone

    Adriamycin and Cyclophosphamide combination

    regimens re-classified as HEC

    23

  • Recommendation by Risk Category, HEC

     2011 Recommendation: Dosing

     Day 1:

     NK1 antagonist (aprepitant 125 mg OR fosaprepitant 150 mg)

     5-HT3 receptor antagonist (options on next slide)

     Dexamethasone 12 mg

     Day 2:

     Dexamethasone 8 mg + if NK1 antagonist = aprepitant, then aprepitant 80 mg

     Day 3:

     Dexamethasone 8 mg (dexamethasone may be given for 3 or 4 days) + if NK1

    antagonist = aprepitant, then aprepitant 80 mg

    24

  • Recommendation by Risk Category, HEC

    5-HT3 Receptor Antagonist Dosing

    5-HT3 Receptor

    Antagonist Intravenous Oral

    Granisetron 1 mg or 0.01 mg/Kg 2 mg

    Ondansetron 8 mg or 0.15 mg/Kg 8 mg twice daily

    Palonosetron 0.25 mg 0.50 mg

    Dolasetron 100 mg IV formulation NOT

    recommended

    Ramosetron 0.3 mg ---

    Tropisetron 5 mg 5 mg

    25

  • Olanzapine: HEC

     A pilot study, compared olanzapine with aprepitant,

    both in combination with palonosetron and

    dexamethasone.

     Patients randomly assign