4 5T H 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 C L I N I C A L P H A R M A C I S T M U N S O N M E D I C A L C E N T E R T R A V E R S E C I T Y, M I C H I G A N
The
“N”
Factor:
Prevention & Treatment of
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
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
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
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
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
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/VPhysiology 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
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
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
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
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 NervesAbdominal Diaphragm Stomach Esophagus
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.
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 emesisHIGH 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)
MODERATE Risk (31-90%)
Aldesleukin >12-15 MIU/m2 Amifostine <300mg/m2 Arsenic trioxide Azacitidine Bendamustine Busulfan Carboplatin Carmustine </=250mg/m2 Cisplatin <50mg/m2 Clofarabine Cyclophosphamide </=1.5g/m2 Cytarabine >200mg/m2 Dactinomycin Daunorubicin Doxorubicin </=60mg/m2 Epirubicin </=90mg/m2 Idarubicin Ifosfamide <10g/m2 Interferon alfa >/=10 MIU/m2 Irinotecan
Melphalan
Methotrexate >/=250mg/m2 Oxaliplatin
temozolomide
LOW Risk (10-30%)
Amifostine </=300mg/m2
Aldesleukin </=12 MIU/m2
Cabazitaxel
Cytarabine 100-200mg/m2
Docetaxel
Doxorubicin (liposomal)
Eribulin
Etoposide
5-Fluorouracil
Floxuridine
Gemcitabine
Interferon alfa >5<10
MIU/m2
Ixabepilone
Methotrexate >50mg/m2
<250mg/m2
Mitomycin
Mitoxantrone
Paclitaxel
Paclitaxel-albumin
Pemetrexed
Pentostatin
Pralatrexate
Romidepsin
Thiotepa
topotecan
MINIMAL Risk (<10%)
Alemtuzumab Asparaginase Bevacizumab Bleomycin Bortezomib Cetuximab Cladribine Cytarabine <100mg/m2 Decitabine Denileukin diftitox Dexrazoxane Fludarabine Interferon alfa </=5 MIU/m2
Ipilimumab Methotrexate </=50mg/m2 Nelarabine Ofatumumab Panitumumab Pegasparaginase Peginterferon Rituximab Temsirolimus Trastuzumab Valrubicin Vinblastine 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
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, morningsickness 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
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*
*Reference 12
AJ…
Treatment risk:
Cisplatin - Level of emetogenicity = HIGH Etoposide – Level of emetogenicity = LOW
N/V Prophylaxis:
5-HT
3
+ 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*
*Reference 12
New ondansetron max IV = 16mg; PO = 24mg*
Drug Classes Available for Prevention &
Treatment of CINV
Serotonin (5-HT
3) Receptor Antagonists
Neurokinin-1 Receptor Antagonists
Corticosteroids
Dopamine Receptor Antagonists
Phenothiazines Butyrophenones Metoclopramide
Benzodiazepines
Cannabinoids
Serotonin (5-HT
3
) 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)
Serotonin (5-HT
3
) Receptor Antagonists
Adverse effects include:
Headache
Constipation or diarrhea
Transient ECG interval abnormalities (particularly QT
prolongation), often asymptomatic
Somnolence, sedation
Serotonin (5-HT
3
) 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-HT
3
’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-HT
3
’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
Neurokinin-1 (NK1) Receptor Antagonists
Aprepitant
is a substrate, a moderate inhibitor, and aninducer of CYP3A4 when used as a 3-day regimen
Fosaprepitant
,
given as a single dose, is a weak inhibitor ofCYP3A4 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
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
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
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
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
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
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
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
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
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
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
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
References
1. Gralla RJ, et al. Recommendations for the use of antiemetics: Evidence-based clinical practice guidelines. J Clin Oncol
1999;17:2971-16.
2. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J
Clin Oncol. 2011;29:4189-4198.
3. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer (MASCC). Prevention of
chemotherapy- and radiotherapy-induced emesis: Results of the Perugia Consensus Conference. Ann Oncol 2010;21 (Suppl 5):v232-v243.
4. NCCN Guidelines Version 1.2012. Antiemesis. National Comprehensive Cancer Network.
5. Hesketh, PJ. Chemotherapy-Induced Nausea and Vomiting. N Engl J Med 2008; 358:2482-94.
6. The Chemotherapy Source Book, 4th Ed., M.C. Perry. Lippincott 2008.
7. Lohr, LK, Current Practice in the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in Adults. J
Hematol Oncol Pharm. 2011;1(4):13-21.
8. T. Mays. Gastrointestinal Toxicities: Nausea and Vomiting in Oncology Pharmacy Preparatory Review Course, Volume
2. ACCP, ASHP 2011
9. Lohr, L., Chemotherapy-Induced Nausea and Vomiting. The Cancer Journal. Vol 144, No 2, March/April 2008.
10. Roscoe, JA, et al. Prevention of Delayed Nausea: A University of Rochester Cancer Center Community Clinical Oncology
Program Study of Patients Receiving Chemotherapy. J Clin Oncol August 20, 2012. Abstract.
11. Navari, RM et al. Olanzapine Versus Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A
Randomized Phase III Trial. J Supportive Oncol 2011;9:188-195.
12. U.S. Food and Drug Administration. Alert for Ondansetron and QT Prolongation. September 2011. 13. Aapro, MS, et al. Anticipatory Nausea and Vomiting. Support Care Cancer 2005;13:117-21.
14. 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.
15. U.S. Food and Drug Administration. FDA Issues Update on QT Prolongation Risk With Ondansetron. June 29, 2012.
16. Jarkowski, A., et al. The Risk of Neurotoxicity with Concomitant Use of Aprepitant and Ifosfamide. The Oncology Pharmacist;
April 2011.
17. Merck & Co., Inc. Fosaprepitant, Aprepitant Product Information.
