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