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
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Chemotherapy Induced Nausea Vomiting and Cancer Cachexia
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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 <50 years
Women > 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 (<10%)
*Antiemetic risk categories were developed from historic studies
Ascertain that the best regimen is being given for the
emetic risk;
Consider adding lorazepam or alprazolam to the
regimen; and,
Add olanzapine or substitute high-dose
intravenous metoclopramide instead of 5-HT3 receptor
antagonist or add dopamine antagonist.
35
Special Emetic Populations: Anticipatory Emesis
Anticipatory Emesis:
Begins before treatment
May occur in patients with poor control of vomiting during prior
chemotherapy
2011 Recommendation:
Clinicians should always use the antiemetic regimen
recommended for the initial chemotherapy based on emetic risk
Use the most active antiemetic regimens appropriate for
chemotherapy
Behavioral therapy with systematic desensitization
36
Special Emetic Populations:
Pediatric Oncology Patients
Few research trials evaluate antiemetic therapy in children
receiving cancer therapy
2011 Recommendations:
A 5-HT3 receptor antagonist plus a corticosteroid is suggested before chemotherapy in children receiving chemotherapy of HEC or MEC.
Due to variation of pharmacokinetic parameters in children, higher weight-based doses of 5-HT3 receptor antagonists than those used in adults may be required.
37
RADIATION-INDUCED
INDUCED NAUSEA AND
VOMITING (RINV)
38
RINV: Emetic Risk Categories of Radiation
Emetic Risk Irradiated area
High Total Body (TBI)
Total Nodal Irradiation
Moderate
Upper Abdomen
Upper Body Irradiation
Half Body Irradiation
Low Lower Thorax and Pelvis
Cranium, Craniospinal, and Head & Neck
Minimal Extremities
Breast
39
RINV: 5-HT3 Receptor Antagonist Dosing
5-HT3 Receptor Antagonist Dosing
5-HT3 Antagonist Intravenous Oral
Granisetron1
(preferred) 1 mg or 0.01 mg/Kg 2 mg
Ondansetron1
(preferred) 8 mg or 0.15 mg/Kg 8 mg twice daily
Palonosetron2 0.25 mg 0.50 mg
Dolasetron 100 mg IV formulation NOT
recommended
Tropisetron 5 mg 5 mg
1 Preferred agents, 2 No data on dosing frequency available, every 2nd or 3rd day suggested
40
RINV: Moderate Emetic Risk
2011 Recommendation
5-HT3 receptor antagonist, before each fraction and at
least 24 hours after end of XRT, and a 5-day course of
dexamethasone during fractions 1-5.
Dosing: 5-HT3 receptor antagonist as previous slides
Dexamethasone: 4mg oral or IV, fractions 1-5
41
RINV: Moderate Emetic Risk
2011 Recommendation
5-HT3 receptor antagonist before each fraction,
throughout course of radiotherapy.
Patients may be offered a short course of
dexamethasone during fractions 1-5.
Dosing:
5-HT3 receptor antagonist: as previous slides
Consider- Dexamethasone: 4mg oral or IV,
fractions 1-5
42
RINV: Low Emetic Risk
2011 Recommendation
5-HT3 receptor antagonist* as rescue or prophylaxis
For patients who experience RINV while receiving
rescue therapy only, prophylactic treatment should
continue until radiotherapy is complete.
Dosing:
5-HT3 receptor antagonist: as previous slides
43
RINV: Minimal Emetic Risk
2011 Recommendation
5-HT3 receptor antagonist* as rescue or prophylaxis
Prophylactic antiemetics should continue throughout
radiation treatment if a patient experiences RINV while