Chemo-Induced Nausea and Vomiting (CINV)
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Transcript of Chemo-Induced Nausea and Vomiting (CINV)
Chemo-Induced Nausea and Vomiting
(CINV)
Elshami M. Elamin, MDMedical oncologist
Central Cancer Care Centerwww.cccancer.comWichita, KS - USA
Chemo RT Bowel obstruction Brain mets Electrolytes imbalance
Hypercalcemia, Hyponatremia, Hyperglycemia
Uremia Opiates Gastroparesis
(Vincrestine) Psycophysiologic:
Anxiety Anticipating N/V
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 preventN/V
than to treat it
ANTI-EMETICS
Emesis neuroreceptors Serotonin: 5-HydroxyTtryptamine (5-HT3) Dopamine Acetylcholine Corticosteroid Histamine Cannabinoid Opiate Neurokinin-1 (NK-1)
Dopamine antagonists1-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 CNS2- Haloperidol
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
Watch for Dystonic reaction
Prochlorperazine Metoclopramide Domperidone
1- Diphenhydramine
OR
2- Benztropine
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
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
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
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)
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-highlyemetogenic chemo
*Delayed emesis:Days 2-3
Steroids Dexamethasone
Always keep in mind its side effects
*Hyerglycemia*HTN
*Fluid retension*PU
*Osteoporosis
Miscellaneous
Antipsychotic : Olanzapine (zyprexa)
Cannabinol: Dronabinol (marinol) 5-10 mg OR
Nabilone 1-2 mg
Anti-histamine: Promethazine (phenergan)
H2-Blocher or PPI
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
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
Categories of Emetogenic
Chemotherapy
High emetic risk Moderate emetic risk Low emetic risk Minimal emetic risk
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
Potent ematogenic drugs: Potent ematogenic drugs: PlatinumPlatinum DoxorubicinDoxorubicin CytoxanCytoxan DacarbazineDacarbazine
5-HT3 AntagoistD
exa
Apre
pit
an
t
Dopamine antagonist
Lorazepam
PPI/H2-blocker
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
+ 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
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 ofanti-emetic
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
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
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 OROR 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
Low Emetic Risk IV Chemo: (10-30%
frequency of emesis) 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
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
Minimal Emetic Risk IV Chemo
(<10% frequency of emesis)
Alemtuzumab (Campath)
Asparaginase Bleomycin Bortezomib
(velcade) Cetuximab Avastin Cytarabine <100 Fudara
IFN < 5mIU/m MTX < 50mg/m Panitumumab Rituxan Torisel Herceptin Vinblastine Vincristine Vinorelbine
No routine prophylaxis
Moderate to High Emetic Risk Oral Chemo
Busulfan (>4 mg/d) Cytoxan >100 mg/m/d Estramustine VP-16 Lomustine (CeeNU) Procarbazine Temozolomide > 75mg/m/d
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
Minimal to Low emetic Risk Oral Chemo
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
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
PRN N/V
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
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
Second step:
Agents from
different drug
class PRN
N/V controlled
N/V Not controlled
Continue agent on Schedule Not PRN
Re-eval, adjust doseand or new drug
Consider change
antiemetics to
higher level for
next cycle
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
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 ….
Anticipatory N/V
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
Eating small frequent meals Choice of food
Easy on stomach Eating food at room temperature
Dietary consult
Behavioral therapy
Relaxation/systematic desensitization
Hypnosis with guided imagery
Music therapy
Spiritual
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THANKS