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Chemotherapy Induced Nausea Vomiting and Cancer Cachexia

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Diapositiva 1Specialized Residency in Internal Medicine
Faculty of Pharmaceutical Sciences, Khon Kaen University
Advanced Pharmacotherapeutics I, 2012
Categories of CINV
Current guidelines for CINV
guideline: 2011 edition
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
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
patient’s nausea and vomiting
Use pathophysiology knowledge to determine
the likely mechanism and involved receptors
Choose appropriate therapy to target these
receptors
Anticipatory: Prior to chemotherapy
Classification of CINV
Breakthrough
Refractory/Intractable
8
Nausea/ Vomiting
History of vomiting with prior exposure to chemotherapeutic agents
Other risks
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
Primary or metastatic brain
11
Pathophysiology
14
Dopamine antagonists
guideline: 2011 edition
Agency for Healthcare Research and Quality (AHRQ)-
funded Oregon Evidence-Based Practice Center
An ASCO Update Committee considered pertinent literature through
February 2010:
Cancer (MASCC) Meetings
Chemotherapy-Induced Nausea and Vomiting
CINV (cont’d)
19
CHEMOTHERAPY-INDUCED
21
Single Agents Antineoplastics
High Moderate Low Minimal
*These anthracyclines, when combined with cyclophosphamide, are now designated as high emetic risk 22
Recommendation by Risk Category, HEC
2011 Recommendation:
2011 Recommendation: Dosing
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
5-HT3 Receptor Antagonist Dosing
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
25
both in combination with palonosetron and
dexamethasone.
experienced CR rates similar to those of patients
who received aprepitant.
during the overall study period (P.01).
Additional trials are necessary to define the role of
olanzapine in this setting.
26
Navari R, et al. 2010 MASCC, June 24-26, 2010 (abstr 02-010)
Recommendation by Risk Category, MEC
2011 Recommendation:
If palonosetron is not available, any of the first-generation 5-HT3
receptor antagonists may be used- preferably ondansetron or
granisetron
Dosing:
Palonosetron 0.25 g IV OR 0.50 mg oral, day 1 only
Dexamethasone 8 mg (IV or oral), days 1-3
27
may consider its use
If clinicians opt to use aprepitant, dosing:
Aprepitant: 125 mg day 1, 80 mg days 2 and 3
5-HT3 receptor antagonist dosing as previous slide,
no preferred agent
Dexamethasone: 12 mg on day 1 ONLY
*Note: No data available at the time of the update on
fosaprepitant in moderate risk setting
28
2011 Recommendation:
chemotherapy is suggested.
Minimal Emetic Risk:
before or after chemotherapy.
emetic risk
30
adjuncts to antiemetic drugs, but are not recommended as
single agent antiemetics
dexamethasone
31
2011 Recommendation: No published RCT data which met inclusion criteria
(for the systematic review) are currently available to
support a recommendation about such therapies
32
2011 Recommendation:
dexamethasone is recommended.
evidence to support its use is limited.
33
class of the chemotherapy should be administered
for each day of the chemotherapy and 2 days
afterward, if appropriate
cisplatin regimens should receive
Nausea Despite Recommended Prophylaxis
illness, and medications;
Ascertain that the best regimen is being given for the
emetic risk;
regimen; and,
intravenous metoclopramide instead of 5-HT3 receptor
antagonist or add dopamine antagonist.
35
Anticipatory Emesis:
Begins before treatment
May occur in patients with poor control of vomiting during prior
chemotherapy
recommended for the initial chemotherapy based on emetic risk
Use the most active antiemetic regimens appropriate for
chemotherapy
36
receiving cancer therapy
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
Emetic Risk Irradiated area
High Total Body (TBI)
Minimal Extremities
5-HT3 Receptor Antagonist Dosing
5-HT3 Antagonist Intravenous Oral
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
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.
41
throughout course of radiotherapy.
dexamethasone during fractions 1-5.
fractions 1-5
rescue therapy only, prophylactic treatment should
continue until radiotherapy is complete.
Dosing:
43
Prophylactic antiemetics should continue throughout
radiation treatment if a patient experiences RINV while
receiving rescue therapy.
oral or prochlorperazine 10 mg oral or IV
44
radiation therapy and chemotherapy
emetic risk of the chemotherapy, unless emetic risk
with planned radiotherapy is higher.
45
Fosaprepitant
Granisetron transdermal system
Option for multi-day chemotherapy and high or moderate risk
radiation therapy
Ondansetron ODT
46
Moderately emetogenic agents: Palonosetron preferred 5-HT3 receptor antagonist
Low emetogenic agents No change
Minimally emetogenic agents No change
Combination chemotherapy No change
Adjunctive drugs No change
2011Update Recommendation Changes, cont’d
CINV, cont’d
Pediatric Patients No change
High-dose chemotherapy with SCT or BMT Consider the addition of aprepitant to antiemetic regimen
Multi-day chemotherapy Recommended antiemetic regimen for patients receiving 5-day cisplatin:
aprepitant + 5-HT3 receptor antagonist + dexamethasone
Emesis or Nausea despite optimal prophylaxis Option of adding olanzapine to antiemetic regimen
Anticipatory nausea and vomiting No change
48
RINV
• High Risk RINV – Addition of 5-day course of dexamethasone during fractions 1-5
• Moderate Risk – Consider offering 5-day course of dexamethasone during fractions 1-5
• Low risk – 5-HT3 receptor antagonist as either prophylaxis or rescue
– Patients requiring rescue should receive subsequent prophylactic antiemetic
therapy
therapy
49
Chemotherapy Induced Nausea Vomiting
and Cancer Cachexia Management:
Specialized Residency in Internal Medicine
Faculty of Pharmaceutical Sciences, Khon Kaen University
Advanced Pharmacotherapeutics I, 2012
Identify treatment-related nutrition deficiencies in cancer patients and management strategies
Outline the application and limitations of the A.S.P.E.N. Guidelines in the care of patients with cancer
Describe the clinical dilemmas presented with utilizing nutritional support in the various stages of cancer progression
51
B. False
significantly impact quality of life and mortality in
oncology patients. A. True
cancer
Frequency of weight loss in cancer cachexia?
Dewys, et al. Amer J Med. 1980;69:491-497.
Aetiology of Cancer Cachexia
Alterations of metabolic pathways
Host-tumour
interaction
Metabolic
dysregulation
Clinical
endpoints
Neuroendocrine dysregulation
doi:10.1155/2011/601434
57
Intervention Type Effects
Esophagous Gastric stasis, regurgitation, early satiety
Stomach Malabsorption, early satiety, hypoglycemia
Colon Water loss, electrolyte loss
Radiation Acute Diarrhea, bleeding, N/V, mucositis, xerostomia
Chronic Stricture, fibrosis, dysphagia, malabsorption
CMT Cytotoxic Anorexia, NV, mucositis, enteritis, Electrolyte
imbalance, oragan dysfunction
Steroids Fluid/electrolyte imbalances, hyperglycemia
Daly JM, et al. In: ACS Textbook of Clinical Oncology. 1995:580-596.
Roberts S, et al. In: The A.S.P.E.N. Nutrition Support Core Curriculum. 2007:649-675.
Clinical Features
Hypophagia / anorexia
Early satiety
Mild ≥ 5% in 1 mo.
Mod ≥ 7.5 % in 3 mo.
Severe ≥ 10% in 6 mo.
And 3/5
Anaemia (Hb < 12 g/dL)
Note:
• Fatigue is defined as physical and or mental weariness resulting from exertion; an inability to continue exercise at the same intensity with
a resultant deterioration in performance.
Anorexia is defined as limited food intake (total caloric intake less than 20 kcal/kg body weight/day) or poor appetite.
Low-fat-free mass index represents lean tissue depletion (i.e., mid upper arm muscle circumference <10th percentile for age and gender’
appendicle skeletal muscle index by DEXA <5.45 (kg/m2) in females and <7.25 in males).
Evan WJ, et al. Clinical Nutrition 2008;27(6):793–799.
Cancer Cachexia Management
Severe malnutrition
Dietician, pharmacist, physician
Enhance anti-tumour treatment effects
therapies
Increased
Decreased
kcals per day
If not compensated by ↑ energy intake results in loss
of 1.1 - 2.3 kg muscle mass & 0.5 – 1.0 kg body fat /
month
Energy Requirement
expenditure is approx:
(TEE per kg is higher in this group)
Published reference calculations are more accurate for
underweight cancer patients
Vitamin and Mineral Requirement
oncological disease
Inclusion of increased doses of anti-oxidant
vitamins could be considered but at present
lack data to demonstrate clinical benefit
PEN Group, 2004, ASPEN, 2002, Arends et al., 2006
Pharmacologic Agent for Cancer Cachexia
Megestrol acetate 160-1600 mg PO OD
Medroxyprogesterone 300-1000 mg PO OD
Dronabinol 2.5 mg PO BID
Dexamethasone 0.75 mg PO QID
Prednisolone 10 mg PO BID
Endpoints for evaluating interventions
cytokines
reactants
Summary
term” condition
Prophylactic management and control of adverse event
Long term follow-up and assessment of therapy
related complications
therapeutic potential of nutritional support