The “N” Factor:

Prevention & Treatment of

Chemotherapy-Induced Nausea & Vomiting

4 5 TH A N N U A L
G R E AT L A K E S C A N C E R N U R S I N G C O N F E R E N C E
S O M E R S E T I N N , T R O Y, M I C H I G A N
O C TO B E R 2 0 1 2

J O A N N E P. M C G U R N , B S P H A R M , B C O P
CLINICAL PHARMACIST
MUNSON MEDICAL CENTER
T R A V E R S E C I T Y, M I C H I G A N
 Objectives

 For the patient receiving chemotherapy, the

participant will be able to:

 Recognize the patient- and drug- specific risk factors

associated with chemotherapy-induced nausea and vomiting
(CINV).
 Understand antiemetic drug classifications and be able to
develop a plan for adequate anti-emetic prophylaxis and
breakthrough treatment.
 Goal of Anti-Emetic Therapy

 PREVENTION!
 Optimally, no patient should become nauseated or have
vomiting as a result of their cancer treatment
 MINIMIZE
 If nausea/vomiting cannot be prevented,
the goal is to minimize the extent and
duration of symptoms
 RESCUE
 When a patient has been optimally
treated but still has breakthrough
nausea or vomiting
 Guidelines

 NCCN (National Comprehensive Cancer Network)

 Revised several times each year.
 Website: http://www.nccn.org
 NCCN Guidelines – Antiemesis pocket Version 1.2012 available
 ASCO (American Society of Clinical Oncology)
 Updated periodically with most recent in 2011.
 MASCC (Multinational Association of Supportive Care in Cancer)
 Involves nine different oncology organizations from around the world
 Updated every 6-12 months based on specific criteria. Most recent
update 2011.
 Website: http://www.mascc.org
 MAT (MASCC Antiemesis Tool)
 Other contributors:
 Oncology Nursing Society (ONS), American Society of Health-System
Pharmacists (ASHP)
 Use of Guidelines

 Use of guidelines will help to:

 Optimize patient care

 Standardize the ordering, preparation, and administration of

anti-emetic therapies
 Function as an educational tool for new staff

 Provide a systematic method of assessment and adjustment

of treatment in challenging patients
 Aid in predicting volume and containing
the cost of pharmaceuticals
 Definitions…

 Nausea
 The inclination to vomit or a ‘feeling’ in the throat or
epigastric region alerting an individual that vomiting is
imminent
 Usually involves concurrent tachycardia and
hyper-salivation
 Nausea is very subjective

 Response to drug therapy is often

variable
 Definitions…

 Vomiting
 “Reverse peristalsis” – contraction of the
abdominal muscles and diaphragm result in
the expulsion of gastric contents through the
mouth
 Can objectively be quantified
 In general, is responsive to drug therapy
 Retching
 The labored movement of abdominal and
thoracic muscles before vomiting
 Spasmodic and abortive respiratory
movements, distinct from vomiting
 Can objectively be quantified
 Variable response to drug therapy
 Definitions…

 Acute emesis
 Occurs during the first 24 hours after chemotherapy
administration, with the peak seen at about 5-6 hours
 Responsive to drug therapy

 Delayed emesis
 Vomiting occurring after the first 24 hours and, depending on
the offending drug, may last up to 5 days (or longer) after
chemotherapy administration, with peak in 2 to 3 days
 Mechanism involves stimulation of neuroreceptors other than
serotonin
 Patients are at higher risk for developing anticipatory N/V
 Variable response to drug therapy

Lohr,L., Current Practice in the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in Adults. J Hematol Oncol
Pharm. 2011;1(4):13-21.
 Definitions.

 Breakthrough emesis
 Vomiting that occurs on any day of treatment despite
appropriate antiemetic prophylaxis and/or requires the use
of rescue therapy

 Refractory emesis
 Emesis that occurs during subsequent
treatment cycles when antiemetic prophylaxis
and/or rescue have failed in earlier cycles

Roila, F, Hesketh PJ, Herrstadt, J. Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004
Perugia International Antiemetic Consensus Conference. Ann Oncol 2006;17:20-28.
 Definitions…

 Anticipatory Nausea and Vomiting

 A conditioned or learned response to chemotherapy that
develops in up to 25% of patients by the 4th treatment cycle
 Triggered by sights, smells, or sounds and is
due to inadequate control of N/V in the past
 Negative expectations and emotional stress
prior to treatment can also have an impact
on presence or absence of ANV
 Prevention of N/V with initial cycles of
chemotherapy is the best treatment

Aapro MS, Molassiotis, A, Olver, I. Anticipatory Nausea and Vomiting. Support Care Caner (2005) 13: 117-121.
 Causes of Emesis In Cancer Patients

 GIT
 Partial or complete bowel obstruction, gastric outlet
obstruction, constipation (disease or drug induced)
 Gastroparesis
 Tumor or chemotherapy (eg., vincristine) induced
 Other causes (eg., diabetes)
 Liver metastases
 Vestibular dysfunction
 Increase ICP due to brain metastases
 Metabolic imbalance
 Hypercalcemia, hyponatremia
 Uremia, hyperglycemia

 Psychophysiologic
 Anxiety, pain
 Anticipatory N/V

Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94.

 Physiology of CINV

 Complex interaction between receptors in the central and

peripheral nervous systems and neurotransmitters
 Two primary sources of afferent input that can initiate the
emetic reflex following chemotherapy:

Abdominal Vagal Afferents

The Area Postrema

Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94.

 Physiology of CINV

 Abdominal Vagal Afferents

 Appear to contribute the most to
the emetic process
 Contain a variety of receptors at their
terminal ends
 5-Hydroxytryptamine3 (5-HT3)
(serotonin)
 Neurokinin-1 (NK1)
 Cholecystokinin-1
 End receptors are located in close proximity to enterochromaffin
cells in the proximal small intestine which contain local mediators
such as 5-HT (serotonin), Substance P, and cholecystokinin
 In this process, 5-HT is believed to play the most important role

Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94.

 Physiology of CINV

 Abdominal Vagal Afferents

 Chemotherapy stimulates cells in
small intestine, releasing mediators
which bind to the vagal fibers
 Once bound, an afferent stimulus is
carried to the nucleus tractus
solitarius (NTS) in the dorsal brain
stem and subsequently activates the
“central pattern generator”
 The dorsal vagal complex contains
many receptors of significance in
the emetic process including NK1,
5-HT3 and dopamine-2 receptors
Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94.
 Physiology of CINV

 The Area Postrema (previously termed ‘Chemoreceptor Trigger Zone’)

 A circumventricular structure located at the caudal end of
the fourth ventricle
 Blood-brain-barrier is quite permeable in this part of the
brain and is thought to be accessible to blood and
cerebrospinal fluid-borne emetic stimuli
 Opioids can induce emesis
when bound to this area
 It is possible that gut-derived
peptides and chemotherapy
metabolites could also cause
emesis by binding at this site

Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94

 Physiology of CINV

 Amygdala
 An almond-shaped mass of nuclei
located deep within the temporal
lobe of the brain
 It is a limbic system structure
whose primary role is the
processing of memory and
emotional reactions

Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94

Amygdala, Wikipedia.
 Physiology
of CINV

Hesketh PJ. Chemotherapy-induced nausea and

vomiting. N Engl J Med 2008;358:2482-94.
 Reflex Pathways of Vomiting

Central Pattern
Generator

1. Salivatory
Center
2. Vasomotor
Center
3. Respiratory
Center
4. Cranial Nerves

Abdominal Diaphragm Stomach Esophagus

Hesketh,PJ. Chemotherapy-Induced Nausea and Vomiting. NEJM 2008;358:2482-94

 Neurotransmitters

 Four classes of neurotransmitters have been implicated

in CINV
 Dopamine
 The focus of early antiemetic studies
 5-Hydroxytryptamine (5-HT)
 The most important in acute CINV
 Substance P (a member of a group of peptides called tacykinins)
 Binds to neurokinin-1, 2, and 3 receptors
 NK1 receptors are found throughout CNS (including the dorsal vagal
complex) and in the GI tract
 Endocannabinoids
 Unlike the above which have a pro-emetic role, endogenous
cannabinoids exert an agonistic antiemetic effect.
Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94.
How do you determine a
patient’s risk for CINV ?
 Patient-Related Risk Factors

 Patient characteristics that may increase the risk

of CINV:
 Age < 50 years
 Female sex
 No/minimal history of alcohol use
 Prior experience or poor emetic
control with previous chemotherapy
 History of hyperemesis or extreme
morning sickness with pregnancy
 History of motion sickness, depression
or other psychosocial factors
Adapted from multiple resources.
 Treatment-Related Risk Factors

 Categories of Emetic Risk

 HIGH (Level 4)
 >90% frequency of emesis
 MODERATE (Level 3)
 31-90% frequency of emesis
 LOW (Level 2)
 10-30% frequency of emesis
 MINIMAL (level 1)
 <10% frequency of emesis

Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482-94.

 HIGH Risk (>90%)

 Carmustine >250mg/m2
 Cisplatin >50mg/m2
 Cyclophosphamide >1.5g/m2
 Dacarbazine
 Doxorubicin >60mg/m2
 Epirubicin >90mg/m2
 Ifosfamide >10g/m2
 Mechlorethamine
 Streptozocin
 AC combination
(defined as either doxorubicin or epirubicin
with cyclophosphamide)
NCCN Guidelines. Antiemesis Version 1.2012
 MODERATE Risk (31-90%)
 Aldesleukin >12-15 MIU/m2  Dactinomycin
 Amifostine <300mg/m2  Daunorubicin
 Arsenic trioxide  Doxorubicin </=60mg/m2
 Azacitidine  Epirubicin </=90mg/m2
 Bendamustine  Idarubicin
 Busulfan  Ifosfamide <10g/m2
 Carboplatin  Interferon alfa >/=10 MIU/m2
 Carmustine </=250mg/m2  Irinotecan
 Cisplatin <50mg/m2  Melphalan
 Clofarabine  Methotrexate >/=250mg/m2
 Cyclophosphamide  Oxaliplatin
</=1.5g/m2  temozolomide
 Cytarabine >200mg/m2

NCCN Guidelines. Antiemesis Version 1.2012

 LOW Risk (10-30%)
 Amifostine </=300mg/m2  Ixabepilone
 Aldesleukin </=12 MIU/m2  Methotrexate >50mg/m2
 Cabazitaxel <250mg/m2
 Cytarabine 100-200mg/m2  Mitomycin
 Docetaxel  Mitoxantrone
 Doxorubicin (liposomal)  Paclitaxel
 Eribulin  Paclitaxel-albumin
 Etoposide  Pemetrexed
 5-Fluorouracil  Pentostatin
 Floxuridine  Pralatrexate
 Gemcitabine  Romidepsin
 Interferon alfa >5<10  Thiotepa
MIU/m2  topotecan
NCCN Guidelines. Antiemesis Version 1.2012
 MINIMAL Risk (<10%)
 Alemtuzumab  Ipilimumab
 Asparaginase  Methotrexate </=50mg/m2
 Bevacizumab  Nelarabine
 Bleomycin  Ofatumumab
 Bortezomib  Panitumumab
 Cetuximab  Pegasparaginase
 Cladribine  Peginterferon
 Cytarabine <100mg/m2  Rituximab
 Decitabine  Temsirolimus
 Denileukin diftitox  Trastuzumab
 Dexrazoxane  Valrubicin
 Fludarabine  Vinblastine
 Interferon alfa </=5 MIU/m2  Vincristine
 Vinorelbine
NCCN Guidelines. Antiemesis Version 1.2012
 Rule(s) of Thumb

 Combination therapy
 is usually more emetogenic than single agent regimens
 Multiday regimens
 put patient at risk for both acute and delayed N/V
 Emetogenicity is dose-related,
 with high-dose chemotherapy regimens (eg., stem cell transplant
conditioning regimens) being more emetogenic than lower doses
 Emetogenic potential may be different on different
days of treatment –
 antiemetics should be tailored accordingly
 Antiemetic choices should be based on the drug with
the highest level of emetogenicity
 Making it Real…
 AJ is a 46-year old woman who was
recently diagnosed with extensive
stage small cell lung cancer. She is a
non-drinker who stopped smoking 12
years ago. Her past medical history is
significant for depression, morning
sickness with multiple pregnancies and
motion sickness. Her oncologist plans
to use cisplatin 75mg/m2 (day 1) and
etoposide 100mg/m2 (days 1-3) every
28 days to treat her disease.
 What About AJ…

 AJ is a 46-year old woman who was recently

diagnosed with extensive stage small cell lung
cancer. She is a non-drinker who stopped smoking
12 years ago. Her past medical history is significant
for depression, morning sickness with multiple
pregnancies and motion sickness. Her oncologist
plans to use cisplatin 75mg/m2 and etoposide
100mg/m2 every 28 days to treat her disease.
 What About AJ…

 AJ is a 46-year old woman who was recently

diagnosed with extensive stage small cell lung
cancer. She is a non-drinker who stopped smoking
12 years ago. Her past medical history is significant
for depression, morning sickness with multiple
pregnancies and motion sickness. Her oncologist
plans to use cisplatin 75mg/m2 and etoposide
100mg/m2 every 28 days to treat her disease.
 What About AJ…

 AJ is a 46-year old woman who was recently

diagnosed with extensive stage small cell lung
cancer. She is a non-drinker who stopped smoking
12 years ago. Her past medical history is significant
for depression, morning sickness with multiple
pregnancies and motion sickness. Her oncologist
plans to use cisplatin 75mg/m2 and etoposide
100mg/m2 every 28 days to treat her disease.
 What About AJ…

 AJ is a 46-year old woman who was recently

diagnosed with extensive stage small cell lung
cancer. She is a non-drinker who stopped smoking
12 years ago. Her past medical history is significant
for depression, morning sickness with multiple
pregnancies and motion sickness. Her oncologist
plans to use cisplatin 75mg/m2 and etoposide
100mg/m2 every 28 days to treat her disease.
 What should AJ be given to
prevent N/V with treatment?
 Considerations…

 Treatment risk:
 Cisplatin (day 1) - Level of emetogenicity = HIGH

 Etoposide (days 1-3) – Level of emetogenicity = LOW

 Emetic Pattern:
 HIGH Risk = 3 days after last dose of chemotherapy

 MODERATE Risk = 2 days after last dose of chemotherapy

Patient should be protected throughout

the full period of risk
 New Ondansetron max IV = 16mg, PO = 24mg*

(115mg IV Discontinued)

*Reference 12
 AJ…

 Treatment risk:
 Cisplatin - Level of emetogenicity = HIGH

 Etoposide – Level of emetogenicity = LOW

 N/V Prophylaxis: 5-HT3 + NK1 + corticosteroid*

 Palonosetron (Aloxi) 0.25mg IV day 1 +

 Fosaprepitant (Emend) 150mg IVPB, day 1 +

 Dexamethasone 12mg PO/IV day 1,

8mg PO day 2, 8mg PO BID, days 3-4
 Prochlorperazine (Compazine) 10mg PO
Q6hr PRN is ordered for breakthrough N/V
*References 2, 3, 4
 New ondansetron max IV = 16mg; PO = 24mg*

New ondansetron max IV = 16mg, PO = 24mg*

(Discontinued)

*Reference 12
 Drug Classes Available for Prevention &
Treatment of CINV

 Serotonin (5-HT3) Receptor Antagonists

 Neurokinin-1 Receptor Antagonists
 Corticosteroids
 Dopamine Receptor Antagonists
 Phenothiazines

 Butyrophenones

 Metoclopramide

 Benzodiazepines
 Cannabinoids
 Serotonin (5-HT3) Receptor Antagonists

 Block serotonin receptors in two ways:

 Peripherally – by blocking release from enterochromaffin
cells in the GIT
 Centrally – antagonism of central receptors in the medulla

 Agents
 Ondansetron (Zofran)

 Granisetron (Kytril, Sancuso)

 Dolasetron (Anzemet)

 Palonosetron (Aloxi)
 Serotonin (5-HT3) Receptor Antagonists

 Adverse effects include:

 Headache

 Constipation or diarrhea

 Transient ECG interval abnormalities (particularly QT

prolongation), often asymptomatic
 Somnolence, sedation

 Elevated transaminases, dizziness

 Serotonin (5-HT3) Receptor Antagonists

 Role in cancer patients:

 Standard therapy for highly and moderately emetogenic
agents due to efficacy and low adverse effect profiles
 Addition of corticosteroids is synergistic (20% increase in
effectiveness)
 Not as effective as corticosteroids for delayed N/V
 All agents, when administered in equipotent doses, have
similar efficacy and safety
 Palonosetron has longer half-life and more avid receptor binding
 Granisetron (Sancuso) is a patch formulation
 Current guidelines indicate that PO administration is
equivalent to IV administration in efficacy

References 2,3,4.
 5-HT3’s and QT Prolongation

 September 2011, FDA released an alert concerning

an association between Zofran (ondansetron) and
prolongation of QT intervals. The FDA required a
revision of labeling as follows:

 “…to include a warning to avoid use in patients with

congenital long QT syndrome….Additionally,
recommendations for ECG monitoring in patients with
electrolyte abnormalities (e.g., hypokalemia,
hypomagnesemia), CHF, bradyarrhythmias, or in patients
taking other medications that can lead to QT prolongation…”

U.S. Food and Drug Administration. September 15, 2011.

 5-HT3’s and QT Prolongation

 In a subsequent report the FDA made the following

recommendations:
 A recently completed clinical study suggests that a 32mg single IV dose of
ondansetron may affect the electrical activity of the heart (QT interval
prolongation), which could pre-dispose patients to develop Torsades de
Pointes.
 Ondansetron will continue to be used in the prevention and
treatment of CINV; HOWEVER, no single IV ondansetron
dose should exceed 16mg.
 This does not change any of the recommended oral dosing
regimens for ondansetron (max PO dose = 24mg).

U.S. Food and Drug Administration. June 29, 2012.

 Neurokinin-1 (NK1) Receptor Antagonists

 Inhibits the substance P/neurokinin 1 (NK1)

receptor
 Augments the antiemetic activity of 5-HT3 receptor
antagonists and corticosteroids to inhibit acute and delayed
phases of CINV in both highly and moderately emetogenic
regimens
 Do not use as single agent
 Adverse effects may include:
 Fatigue

 Hiccups

 Weakness, dizziness
 Neurokinin-1 (NK1) Receptor Antagonists

 Aprepitant is a substrate, a moderate inhibitor, and an

inducer of CYP3A4 when used as a 3-day regimen
 Fosaprepitant, given as a single dose, is a weak inhibitor of
CYP3A4 and does not induce CYP3A4
 Potential drug interactions include:
 Oral contraceptives (decreased efficacy)
 Warfarin (decreased efficacy)
 Dexamethasone/methylprednisolone (increased efficacy)
 Midazolam (increased efficacy)
 CYP3A4 inhibitors (increase aprepitant AUC)
 Erythromycin, itraconazole, ketoconazole, etc
 CYP3A4 inducers (decrease aprepitant AUC)
 Carbamazepine, phenytoin, rifampin
Merck & Co., Inc. Product Information. 2009.
 Neurokinin-1 (NK1) Receptor Antagonists

 Chemotherapeutic agents known to be metabolized

by CYP3A4
 docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide,
imatinib, vinorelbine, vinblastine, vincristine
 Doses were not adjusted when used concurrently with etoposide,
vinorelbine, or paclitaxel in phase III trials, but caution is
warranted
 Ifosfamide neurotoxicity
 Recent study found no association between aprepitant use and
the risk of neurotoxicity in patients receiving ifosfamide-based
therapy; caution is warranted

Jarkowski,A., et al. The Risk of Neurotoxicity with Concomitant Use of Aprepitant and Ifosfamide. The Oncology Pharmacist; April 2011.
Product Information. Merck & Co.
 Neurokinin-1 (NK1) Receptor Antagonists

 Dosing
 ORAL
 Aprepitant 125mg PO day 1, 80mg PO days 2 and 3 +
 5-HT3 of choice day 1
 Dexamethasone 12mg PO day 1, 8mg PO days 2, 3, 4

 IV
 Fosaprepitant 150mg IV day 1 (only)
 5-HT3 of choice day 1
 Dexamethasone 12mg PO day 1, 8mg PO day 2, 8mg PO BID days
3 and 4

Merck & Co., Inc. Product Information.

 Fosaprepitant (Emend IV)

 Important points:
 Final solution concentration 1mg/ml in NS
 Administer over at least 20-30 minutes using PVC-free tubing;
increase administration time and/or solution volume if vein
irritation develops
 Incompatible with divalent cations like magnesium and
calcium; infuse through NS line only
 Incompatible with palonosetron (Aloxi) – flush pre/post with
NS
 Compatible (admix or Y-site) with ondansetron or granisetron
and dexamethasone or methylprednisolone
 May cause hypersensitivity reactions (contains the same base
as contained in docetaxel)
Merck & Co., Inc. Medical Information. Nov. 2010.
 Corticosteroids

 General:
 Dosing:
 Dexamethasone dose ranges from 8-20mg
 Methylprednisolone dose ranges from 40-125mg
 Reduce dose when used with aprepitant/fosaprepitant
 Do not give additional steroid if present in treatment regimen
 Adverse effects from single and short courses less frequent, but
may include:
 Euphoria, anxiety, insomnia
 Increased appetite
 Hyperglycemia
 Mild fluid retention
 When IV doses are given too rapidly patient may experience
transient and intense perianal, vaginal, or anal burning
References 3,4.
 AJ…
 Presents to clinic 5 days after her first
cycle of cisplatin and etoposide. She
states that she had continuous nausea
with several episodes of emesis and is
considering no further therapy.
 She has been using prochlorperazine
(Compazine) without significant
benefit.

What would be a reasonable

recommendation now ?
 Breakthrough Considerations…

 If patient has no N/V – don’t change anything

 If patient has N/V, choose an agent with a different
mechanism of action and add ‘PRN’ to current regimen
 Take patient-specific characteristics into consideration
 Anxiety, depression, concurrent medications, dyspepsia

 Multiple concurrent medications may be required

 If N/V controlled, continue breakthrough medication(s) on

scheduled basis

NCCN Guidelines. Antiemesis. Version 1.2012.

 Breakthrough Considerations…

 If N/V uncontrolled:
 Consider changing antiemetic therapy to higher-level primary
treatment
 Consider adding aprepitant/fosaprepitant
 Add other antiemetics, such a dopamine antagonists,
butyrophenones
 Adjust intensity or frequency of 5-HT3
 Changing to a different 5-HT3 may be of questionable benefit
 If treatment goal is non-curative, consider different
chemotherapy regimen
 Adding an anxiolytic to combination antiemetics
 Consider antacid, H2 antagonist or PPI therapy in patients
with dyspepsia
NCCN Guidelines. Antiemesis. Version 1.2012.
 Dopamine Antagonists

 Phenothiazines – effective with moderately and mildly

emetogenic agents; delayed N/V
 Prochlorperazine (Compazine)
 Dose: 10mg PO/IV/IM every six hours (max of 40mg/day); 25mg Supp PR
Q12hr
 Promethazine (Phenergan)
 Not a very potent antiemetic for cancer patients
 Recent shortages of Compazine IV have increased use
 12.5-25mg PO every 4 hours
 25mg PO Phenergan ~ = 6.25mg IV Q 4-6 hours
 Strong vein irritant with possible tissue damage on extravasation; give IV via
central line
 Adverse effects (class)
 Sedation (especially with IV Phenergan and in elderly)
 Hypotension
 Akathisia and dystonia
 Dopamine Antagonists

 Metoclopramide (Reglan)
 Dopamine antagonist at lower doses; serotonin antagonist at
high doses
 Use in breakthrough N/V
 Dosing: 10-20mg PO/IV Q6hr PRN
 Most common adverse effects – diarrhea, dystonia

 Haloperidol (Haldol)
 Used in breakthrough N/V
 Dosing: 0.5-1mg PO/IV/IM Q6hr PRN
 Most common adverse effects – drowsiness, dystonia, dry
mouth
 AJ…
 The addition of metoclopramide is a
very reasonable choice.
 10-20mg PO Q6hr

 If she responds favorably, this should

be added as a scheduled med to her
regimen with the next cycle.
 If not, consider haloperidol or
olanzapine
 Refractory Nausea & Vomiting

 Olanzapine (Zyprexa)
 An antipsychotic that blocks multiple neurotransmitters in the CNS
including dopamine, serotonin, acetylcholine and histamine
 When compared with aprepitant-based regimens in moderately and
highly emetogenic chemotherapy it is at least as effective in acute N/V
control and more effective in controlling delayed symptoms
 Dosing:
 2.5-10mg/day starting day (HS) before or day of chemotherapy and continue
for 5-10 days
 Adverse effects:
 Sedation or sleep disturbance, fatigue, dizziness, dry mouth and weight
gain
 Cautions:
 Use in elderly
 Hyperglycemia; an association with onset of diabetes mellitus
 QT prolongation
Navari,RM., et al. Olanzapine Versus Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Randomized Phase III Trial. J Support
Oncol 2011;9:188-195.
 Cannabinoids

 Approved by FDA for the treatment of CINV in patients

who fail to respond adequately to conventional
antiemetics.
 Dronabinol (Marinol) – 5-10mg PO every 3-6 hours
 Nabilone (Cesamet) – 1-2mg PO BID
 Recommend starting with low
dose to minimize toxicity
 Common adverse effects
 Dizziness
 Drowsiness
 Dysphoria
 Dry mouth
 Other Possibilities…

 In addition to the four primary neurotransmitters,

GABA and histamine receptors may also play a role
in CINV
 Gabapentin (Neurontin)
 Antiemetic action noted in patients with breast cancer who
received gabapentin to help relieve hot flashes
 Antihistamines
 Antiemetic effect may be related to blocking histamine
receptors or by inducing sedation

Lohr,L., Current Practice in the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in Adults. J Hematol
Oncol Pharm. 2011;1(4):13-21.
 Refractory Nausea & Vomiting

 Patients with persistent N/V after chemotherapy

should be evaluated for other possible causes:
 Brain metastases
 Electrolyte abnormalities

 Tumor infiltration of bowel or

other GI abnormalities
 Other comorbidities
 What is AJ at risk for ?
Anticipatory Nausea & Vomiting !!
 Risk Factors for Anticipatory N/V

 Age < 50 years

 N/V after last chemotherapy administration described
as “moderate, severe or intolerable”
 Feeling “warm or hot all over” after last chemotherapy
administration
 Susceptibility to motion sickness
 History of anxiety or depression
 Anticipatory anxiety (also a conditioned response to adverse
stimuli) is more prevalent than ANV
 Experiencing “sweating” and/or “generalized
weakness” after last chemotherapy administration
Aapro, MS., et al. Anticipatory nausea and vomiting. Support Care Cancer 2005;13:117-21.
 Anticipatory Nausea & Vomiting

 Not typically associated with stimulation of

neuroreceptors
 Stimuli most frequently associated with ANV were olfactory
(smell) and cognitive
 Most literature describes observational
versus experimental studies
 Good News ~ there is much less observed
ANV now than in older studies!
 Treatment includes pharmacologic
and non-pharmacologic methods
Aapro MS, Molassiotis, A, Olver, I. Anticipatory Nausea and Vomiting. Support Care Caner (2005) 13: 117-121.
 Benzodiazepines

 Antianxiety agents may be helpful in ANV or used to

treat breakthrough CINV
 They may delay the onset of ANV and help to control sleep
disturbances related to diagnosis and chemotherapy
 Affect the limbic system and cortical input into the
medulla
 Agents commonly recommended:
 Lorazepam
 Alprazolam
 Adverse effects
 Sedation, dizziness, amnesia,
respiratory depression
Lohr,L., Chemotherapy-Induced Nausea and Vomiting. The Cancer Journal. Vol 14, No.2, March/April 2008, pg 85-93.
 Important Principles

 Evaluate each patient individually

 Evaluate the emetogenic potential and pattern of
the chemotherapeutic regimen to be given
 Antiemetics are most effective when given
prophylactically
 Flexibility is the key
The End
 References
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