CLINICAL

CLINICAL

Review aRticle

Chemotherapy-Induced Nausea
and Vomiting: Optimizing Prevention
and Management
Kamakshi v. Rao, PharmD, BcOP, cPP; aimee Faso, PharmD, BcOP, cPP

Background: Nausea and vomiting are serious side effects of cancer chemotherapy that
can cause significant negative impacts on patients’ quality of life and on their ability to toler-
ate and comply with therapy. Despite advances in the prevention and management of
chemotherapy-induced nausea and vomiting (CINV), these side effects remain among the
most distressing for patients.
Objective: To discuss CINV and the current pharmacologic approaches to its management.
Stakeholder Perspective, Discussion: This article outlines the mechanism of CINV, followed by a review of current
page 240 approaches to pharmacologic therapy and current practice guidelines from national cancer
organizations. This information will help providers and payers understand the optimal man-
Am Health Drug Benefits. agement of patients with CINV, including practical considerations and value-based decision-
2012;5(4):232-240 making that considers cost issues.
www.AHDBonline.com Conclusion: Numerous preventive and treatment options are available to manage CINV.
Disclosures are at end of text
Addressing antiemetic regimens requires ongoing patient evaluation to determine the best
approach for each individual patient.

N
ausea and vomiting are 2 serious and related side and history of motion or morning sickness are clear risk
effects of cancer chemotherapy. These adverse factors for nausea and vomiting.5,6 Younger age has also
effects can cause significant negative impacts on been correlated with increased risk, although this may be
patients’ quality of life and on their ability to comply explained by the more aggressive chemotherapy regi-
with therapy. Also, nausea and vomiting can result in mens that tend to be administered to younger patients
anorexia, decreased performance status, metabolic who have more aggressive diseases.5-7 Finally, alcohol
imbalance, wound dehiscence, esophageal tears, and intake tends to be inversely correlated with the risk of
nutritional deficiency.1,2 Despite advances in the preven- developing CINV. Many factors contribute to the treat-
tion and management of chemotherapy-induced nausea ment-specific risk, including (1) the emetogenicity of
and vomiting (CINV), these side effects remain among the agents being used, (2) the dose and schedule of each
the most distressing for patients. The use of emerging agent, and (3) in the case of radiation-induced or post-
antiemetic medications has reduced the incidence of operative nausea, the site of radiation or surgery.
vomiting substantially, but evaluations show that “Emetogenicity” refers to an agent’s tendency to cause
approximately 30% to 60% of patients still experience nausea and/or vomiting. Initially described in 1997, the
either acute or delayed nausea after chemotherapy.3 emetogenicity scale, also known as the Hesketh scale,
Serial evaluations throughout the 1980s and into the divided chemotherapy agents and doses into 5 levels,
2000s show that, although vomiting has fallen further based on their likelihood to cause CINV.9 Since then,
down on the list of side effects that patients perceive as the American Society of Clinical Oncology (ASCO)
being their most severe, nausea remains either the first or and the National Comprehensive Cancer Network
second most severe side effect of chemotherapy.4-8 (NCCN) have modified this scale to be divided into the
Risk factors for CINV can be divided into patient- following 4 categories10,11:
specific and treatment-specific risk factors. Female sex • Highly emetogenic: medications or doses that cause
CINV in >90% of patients
Dr Rao is an oncology/BMT clinical pharmacist practitioner • Moderately emetogenic: medications that induce CINV
and Dr Faso is a hematology/oncology clinical pharmacist in 30% to 90% of patients
practitioner, University of North Carolina Hospitals and • Low emetogenic: medications that are associated with
Clinics, Chapel Hill, NC. CINV rates of 10% to 30%

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 Chemotherapy-Induced Nausea and Vomiting

• Minimally emetogenic: medications that cause CINV KEY POINTS

in <10% of patients.
“CINV” is a broad term used to describe the many ➤ Risk factors for CINV can be either patient-specific
types of nausea and vomiting that can occur in patients or treatment-specific.
with cancer. The major subtypes of nausea and vomiting ➤ Treatment-specific risks include emetogenicity of the
associated with chemotherapy are12-16: agents used, the dose and schedule of each agent,
• Acute: onset of nausea and vomiting within minutes and, if applicable, the radiation or surgery site.
to hours after administration of chemotherapy and ➤ Agents available to treat CINV include 5-HT3
resolving within 24 hours receptor antagonists, NK1 receptor antagonists, and
• Delayed: occurs 24 hours or later after administration corticosteroids, as well as dopamine receptor
of chemotherapy antagonists, benzodiazepines, olanzapine, and
cannabinoids.
• Anticipatory: occurs before chemotherapy administra-
tion; thought to be an indicator of previous poor con- ➤ Guidelines from the NCCN and ASCO can help
trol of nausea and vomiting providers personalize the antiemetic regimens for
their patients, but these are only starting points; a
• Breakthrough/refractory: nausea and vomiting that “value judgment” must also be made.
occur despite appropriate prophylaxis; requires the
use of rescue medications.
➤ The preferred status for palonosetron was derived
from data in 3 of 4 trials showing significant benefits
Because there are so many independent and variable in the delayed setting; these trials had significant
risk factors that can influence the risk for CINV in any flaws in design, leading us to question this
particular patient, it becomes paramount for providers to “preferred” status and suggest that all 5-HT3 receptor
individualize the approach to the prevention and treat- antagonists are equal if used at equivalent doses and
ment of CINV in every patient case. schedules.
➤ Providers must consider clinical, logistic, safety, and
Pathophysiology of Nausea and Vomiting cost factors when treating CINV, and antiemetic
The vomiting response is controlled centrally by the regimens for a particular patient must be evaluated
emetic center, which lies in the reticular formation of and then reevaluated at every treatment cycle.
the brain stem. The emetic center receives input from 3
sources: the periphery, the cortex, and the chemorecep-
tor trigger zone. Peripheral pathways are mediated main-
ly by serotonin (5-hydroxytryptamine3 [5-HT3]) and neu- receiving cisplatin-based regimens, and they subsequent-
rokinin (NK). The cortical pathway, which is responsible ly showed it to be superior to metoclopramide in patients
for anticipatory emesis, is mediated by dopamine and receiving cisplatin and noncisplatin regimens.18-22
histamine. The chemoreceptor trigger zone, which is a Currently, four 5-HT3 receptor antagonists are available
collection of neurons at the base of the brain and is in the United States—ondansetron, granisetron,
exposed to the body’s general circulation, mediates sig- dolasetron, and palonosetron. Palonosetron, the newest
nals through all of the above chemokines. Once the agent, was approved in 2003. These agents are believed
emetic center has been triggered, signals are then sent to to prevent CINV by antagonizing 5-HT3 receptors either
the salivatory, vasomotor, respiratory, and cranial centers peripherally on vagal nerve terminals and/or centrally in
to activate the organs involved with the vomiting reflex, the chemoreceptor trigger zone.23-27 Since their introduc-
namely the abdominal muscles, diaphragm, stomach, tion, 5-HT3 receptor antagonists have become part of the
and esophagus.17 cornerstone for CINV prevention, thanks to their effec-
tiveness and tolerable side-effect profile. The most com-
Pharmacologic Treatment Options for CINV mon adverse effects reported (in their respective package
Available Agents insert) with these agents are headache and constipation.
Before the 1980s, CINV was primarily managed Transient elevation of liver function enzymes and QTc
with dopamine receptor antagonists. Today, we have a prolongation have also been noted.
multitude of options available, targeting the various NK1 receptor antagonists. NK1 receptor antagonists
pathways of the process, to use in the prevention and inhibit substance P in peripheral and central emetic
management of CINV. pathways. Aprepitant was the first drug in this class to
5-HT3 receptor antagonists. Ondansetron was the first be approved by the FDA in 2003. Aprepitant was
US Food and Drug Administration (FDA)-approved 5- approved at doses of 125 mg orally on day 1 and 80 mg
HT3 antagonist in 1991. Early trials showed that orally on days 2 and 3 for the prevention of nausea and
ondansetron was an effective antiemetic for patients vomiting in patients receiving highly emetogenic or

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 CLINICAL

moderately emetogenic single-day chemotherapy.28 Additional Options

Aprepitant was approved after 2 trials showed that the Dopamine receptor antagonists. Before the approval
combination of aprepitant, ondansetron, and dexa- of the 5-HT3 antagonists, dopamine receptor antagonists
methasone decreased emesis or decreased the use of res- were the primary antiemetics used for CINV. With the
cue medications for patients receiving highly emeto- current availability of more effective preventive agents,
genic chemotherapy during the acute and delayed dopamine receptor antagonists are mostly used in the
phases.29,30 The most common adverse effects include management of breakthrough or refractory emesis. The
fatigue, headache, anorexia, diarrhea, hiccups, and dopamine antagonists are divided into phenothiazines
increased transaminases. (eg, prochlorperazine), butyrophenones (eg, haloperidol,
Aprepitant is primarily metabolized by cytochrome droperidol), and substituted benzamides (eg, metoclo-
(CY)P-450 3A4 with minor metabolism by CYP-1A2 pramide). These agents antagonize the dopamine (D2)
and CYP-2C9.28,31 Aprepitant has been shown to be an receptor in the chemoreceptor trigger zone.45,46
inhibitor of CYP-3A4 and an inducer of CYP-2A9. Metoclopramide antagonizes dopamine, but at high doses
Coadministration with corticosteroids such as dexa- it also has activity against the 5-HT3 receptor.47,48
methasone, a CYP-3A4 substrate, causes an increase in Common side effects of dopamine receptor antagonists,
plasma concentrations of dexamethasone. Therefore, which include extrapyramidal symptoms, dystonia, and
when aprepitant is given with dexamethasone for drowsiness, make them more suitable for breakthrough
CINV prevention, the dexamethasone dose should be nausea rather than for primary prophylaxis.
reduced. Because aprepitant is a weak inducer of CYP- Benzodiazepines. These agents are anxiolytics that
2C9, the metabolism of warfarin can be affected. A are used in patients receiving chemotherapy. Benzodi-
decrease of international normalized ratio has been azepines are appropriate adjunct therapies to decrease
noted with this combination, and patients should be treatment-related anxiety, and they are the preferred
monitored, although no empiric dose adjustments for agents to treat and prevent anticipatory nausea and
warfarin are recommended.32 vomiting.49-51 Lorazepam and alprazolam are the primary
Fosaprepitant, which was approved in 2008, is a agents used in this class, with sedation being the most
water-soluble prodrug of aprepitant that is administered common adverse effect, based on our clinical practice
intravenously before chemotherapy.33 Fosaprepitant is experience.
used as an intravenous (IV) 150-mg dose on day 1 only. Olanzapine. This atypical antipsychotic has antago-
The one-time 150-mg IV dose has been shown to be nist activity at adrenergic receptors, muscarinic recep-
noninferior to the 3-day oral aprepitant regimen.34 tors, and multiple dopamine (D1-4) and serotonin recep-
Corticosteroids. Corticosteroids were first shown to tors (5-HT2A, 5-HT2C, 5-HT3, 5-HT6).52,53 Several trials
be efficacious for CINV in the 1980s, and they are now have shown that olanzapine safely and effectively pre-
considered a mainstay of antiemetic regimens for the vents acute, delayed, and refractory CINV when com-
prevention of acute and delayed emesis.10,11,35 Although bined with other antiemetics in patients receiving
not approved by the FDA for CINV, corticosteroids moderately and highly emetogenic chemotherapy.54-56
have been found to be beneficial when used alone for Adverse effects such as sedation, weight gain, orthostatic
the prevention of nausea and vomiting in patients hypotension, hyperglycemia, and a black box warning
receiving low emetogenic chemotherapy and to for increased mortality in elderly patients with demen-
improve efficacy when combined with 5-HT3 receptor tia-related psychosis limit its use.57
antagonists in patients receiving moderately or highly Cannabinoids. Dronabinol and nabilone are 2
emetogenic chemotherapies.36-39 Dexamethasone is the cannabinoids that are currently approved by the FDA for
recommended corticosteroid according to current CINV in patients who have not adequately responded to
guidelines, although no studies have been performed conventional antiemetics. Cannabinoids are thought to
comparing available corticosteroids.10,11 prevent nausea and vomiting by antagonizing cannabi-
The mechanism of action of corticosteroids as noid receptor CB1 in the CNS and possibly CB2 recep-
antiemetic agents has not been elucidated, but it may tors as well.58 Cannabinoids have been shown to be as
be related to activity in the peripheral nervous system effective as or slightly more effective than dopamine
or in the central nervous system (CNS), and possibly receptor antagonists.59,60 Only 1 trial has directly com-
by antagonizing serotonin receptors.40-43 Tolerability to pared a cannabinoid with standard treatment.61
corticosteroids can be a concern, because when used for Ondansetron with dexamethasone plus dronabinol was
the prevention of delayed nausea and vomiting, com- found to be equally efficacious to ondansetron, dexa-
mon adverse effects have included insomnia, epigastric methasone, and placebo.61 This lack of added benefit has
discomfort, agitation, weight gain, and hyperglycemia.44 limited the use of cannabinoids in the preventive set-

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 Chemotherapy-Induced Nausea and Vomiting

Table 1 Recommended Antiemetic Regimens for CINV Prophylaxis

Emetic risk Treatment for acute phasea Treatment for delayed phase
High 3-drug combination treatment with an NK1 receptor NK1 receptor antagonist if oral
antagonist, a 5-HT3 receptor antagonist, and dexamethasone route was used; dexamethasone
Moderate 2-drug combination treatment with a 5-HT3 receptor Dexamethasone
antagonist and dexamethasone
Low Dexamethasone
Minimal No routine prophylaxis recommended
All patients should have “as-needed” rescue medication available, which can include prochlorperazine, promethazine,
a

or lorazepam, regardless of emetic risk level.

5-HT indicates serotonin; CINV, chemotherapy-induced nausea and vomiting; NK, neurokinin.

ting. In addition, vertigo, euphoria, and somnolence are organizations state that behavioral therapy, including
adverse effects that limit the use of cannabinoids. desensitization, is recommended for treatment of ANV.
The NCCN guidelines recommend the use of benzodi-
Current Practice Guidelines azepines to treat ANV.
Practice guidelines from the NCCN and ASCO are For radiation-induced nausea and vomiting, 5-HT3
available to help providers determine optimal prophylax- receptor antagonists are the preferred class of antiemetic.
is and the treatment of CINV.10,11 The NCCN Antiemesis The NCCN divides types of radiation into high risk
GuidelineTM, a consensus-based guideline that incorpo- (eg, total body irradiation), moderate risk (eg, radiation
rates evidence and expert opinion to make recommenda- to upper abdomen), and combined radiation with
tions, is revised annually.11 ASCO guidelines are purely chemotherapy.11 For moderate- and high-risk radiation,
evidence-based guidelines and are updated periodically; granisetron or ondansetron before each radiation treat-
the last update was in 2011.10 Table 1 summarizes specific ment, with or without dexamethasone, is recommended.
recommendations for antiemesis from the NCCN and Prophylaxis of nausea and vomiting with combination
from ASCO. For CINV, both guidelines outline primary chemotherapy and radiation is determined by the eme-
prophylaxis based on the emetogenicity of the patient’s togenic potential of the chemotherapy.
chemotherapy: high, moderate, low, and minimal. ASCO categorizes emetogenic risk of radiation as
For patients receiving highly emetogenic chemother- high (eg, total body irradiation), moderate (eg, upper
apy, both guidelines recommend a 3-drug combination abdomen), low (eg, head and neck), minimal (eg,
that includes a 5-HT3 receptor antagonist, an NK1 breast), and combination of radiation and chemothera-
receptor antagonist, and dexamethasone to prevent py.10 For moderate- and high-risk radiation, a 5-HT3
CINV. The NCCN specifies that the preferred 5-HT3 receptor antagonist before each radiation treatment,
receptor antagonist for highly emetogenic chemotherapy along with dexamethasone during fractions 1 to 5, are
is palonosetron,11 whereas ASCO does not list a pre- recommended. Granisetron and ondansetron are pre-
ferred 5-HT3 receptor antagonist. ferred 5-HT3 receptor antagonists in this setting, but
For patients receiving moderately emetogenic dolasetron can be considered. Palonosetron is listed as an
chemotherapy, the NCCN and ASCO recommend a 2- option, although there are no trials to indicate appropri-
drug combination of a 5-HT3 receptor antagonist, ate dosing frequency. Patients receiving radiation with a
preferably palonosetron, with dexamethasone. Dexa- low risk for nausea and vomiting can be offered a 5-HT3
methasone is recommended by both organizations for receptor antagonist or a dopamine receptor antagonist,
the prevention of CINV in patients with low or minimal such as metoclopramide or prochlorperazine, as a rescue
emetogenic potential. The NCCN also lists metoclo- treatment. Prophylaxis for nausea and vomiting for
pramide or prochlorperazine as possible alternatives. For patients receiving a combination of chemotherapy and
patients receiving minimal-risk chemotherapy, no med- radiation is determined by the chemotherapy regimen,
ications are recommended primarily as prophylaxis. unless the radiation causes a higher risk.
For anticipatory nausea and vomiting (ANV), ASCO
and the NCCN recommend that prevention with opti- Practical Considerations
mal primary prophylaxis is the best approach.10,11 Both Even with the current published guidelines, there are

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 CLINICAL

Table 2 Dosing Ranges for Antiemetics Used for Primary Prophylaxis of CINV
Antiemetic Dose Antiemetic Dose
NK1 receptor antagonists Granisetron 2 mg oral or 1 mg oral
twice daily; 1 mg IV or
Fosaprepitant 150 mg IV 0.01 mg/kg IV
Aprepitant 125 mg oral on day 1 Dolasetron 100 mg oral
and 80 mg oral on
days 2 and 3 Palonosetron 0.25 mg IV
5-HT3 receptor antagonists Corticosteroid
Ondansetron 16-24 mg oral; 8 mg IV Dexamethasone 8-20 mg oral IV
5-HT indicates serotonin; CINV, chemotherapy-induced nausea and vomiting; IV, intravenous; NK, neurokinin.

Table 3 Pharmacokinetic Properties of 5-HT3 Receptor Antagonists

Agent Ondansetron Granisetron Dolasetron Palonosetron
Half-life (hrs) 3-4 7-9 7-8 40
Oral bioavailability, % 56 60 75 N/A
Renal elimination, % 5 12 67 42
Hepatic metabolism CYP-3A, CYP-1A, CYP-3A CYP-3A, CYP-3A4,
CYP-2D6, CYP-2E1 CYP-2D6 CYP-2D6, CYP-1A2
5-HT indicates serotonin; CYP, cytochrome P; N/A, not applicable.

unique challenges for clinicians who manage patients ondansetron, granisetron, and dolasetron.64 This results
with CINV or patients at risk of developing CINV. In this in altered dosing recommendations for palonosetron,
article, we focus on the following 3 practical challenges. which is dosed once per cycle rather than on a daily basis.
1. Are all 5-HT3 receptor antagonists created equal? As discussed earlier, the NCCN and ASCO guide-
Currently, there are four 5-HT3 antagonists available in lines have stated a preference for palonosetron for the
the US market—dolasetron, granisetron, ondansetron, prevention of CINV. These recommendations are based
and palonosetron. Studies with these agents show rela- on data from 4 trials.66-69 In 3 of these trials, palonosetron
tively similar rates of success in the prevention of CINV was compared with various other 5-HT3 receptor antag-
in patients receiving cisplatin-based chemotherapy reg- onists to determine noninferiority.67-69 Only 1 trial was
imens. In addition, studies have established acceptable designed to detect superiority in the comparison.66 All 4
oral:IV conversions that result in similar levels of eme- trials demonstrated similar success rates in preventing
sis control. Equivalent doses and pharmacokinetic acute CINV between palonosetron and the comparator.
properties of the agents are listed in Table 2 and Table The preferred status for palonosetron was derived from
3. When used in equivalent doses, ondansetron, the data showing significant benefits for palonosetron in
granisetron, and dolasetron are considered similar for the the delayed setting in 3 of the 4 trials, including the trial
prevention of nausea and vomiting.62,63 The pharmacoki- sized to measure superiority.
netics of ondansetron, granisetron, and dolasetron are All of these trials, however, had significant flaws in
slightly different, but not enough to result in any clini- their design. Most notable, all of the trials compared a
cally significant differences. single dose of palonosetron to a single dose of the com-
Palonosetron differs from the other 5-HT3 antagonists parator 5-HT3 receptor antagonist. Given palonosetron’s
by having increased binding affinity to the 5-HT3 extended half-life of 40 hours, compared with the half-
receptor, higher potency, and a longer half-life.64,65 The lives of between 3 and 8 hours for other 5-HT3 receptor
half-life of palonosetron is approximately 40 hours antagonists, comparisons at any time after 24 hours are
compared with the significantly lower half-lives of pharmacokinetically irrelevant. In addition, only 1 of

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 Chemotherapy-Induced Nausea and Vomiting

Figure Proposed Value-Based Decision Algorithm for CINV

Clinical success
➤
Convenience Safety Cost

➤
➤
Appropriate –Likelihood of Consideration of –Cost per dose
selection of initial adherence adverse effects –Cost per cycle
therapy based on –Health literacy 5-HT3: QTc –Cost of
patient- and –Complexity of prolongation, hospitalization
treatment- regimen headache, for breakthrough
specific risk constipation
factors Steroids:
hyperglycemia
D2 antagonists:
drowsiness,
extrapyramidal
syndrome
➤

➤
➤

Guideline- Patient’s
based Incorporate value-based considerations optimal
therapy therapy

5-HT indicates serotonin; CINV, chemotherapy-induced nausea and vomiting.

the trials mandated the use of corticosteroids, which bleomycin, etoposide, and cisplatin for testicular cancer
are the backbone of any combination antiemetic regi- and showed favorable results.70 Another study evaluated
men.69 Given these significant flaws in design, we call the use of aprepitant in combination with granisetron
into question the “preferred” status of palonosetron and and dexamethasone, in patients receiving multiday
instead endorse the idea that all 5-HT3 receptor antag- highly emetogenic and moderately emetogenic
onists are indeed equal if used at equivalent doses and chemotherapy. Aprepitant was administered as 125 mg,
schedules. followed by 80 mg daily for the remainder of chemother-
2. Multiday chemotherapy. Most data on the use of apy days, and continued for 2 more days, all along with
5-HT3 receptor antagonists, especially NK1 receptor dexamethasone. This study demonstrated a complete
antagonists, are in the setting of single-day chemothera- remission rate of almost 58% in highly emetogenic and
py. However, numerous malignancies are treated with 73% in moderately emetogenic regimens.71
multiple sequential days of chemotherapy, often with 3. Breakthrough/refractory nausea and vomiting.
various agents being given on different days. Current Breakthrough/refractory nausea and vomiting are chal-
guidelines recommend using the appropriate level of lenging to treat. In particular, refractory nausea and
prophylaxis, according to the emetogenicity of the regi- vomiting may cause significant morbidity, including
men, on each day of the regimen, and continuing weight loss, metabolic imbalances, and nutritional defi-
delayed prophylaxis for 2 to 3 days after the completion ciency, and may result in the inability of patients to
of chemotherapy.10,11 In patients receiving moderately remain on their therapy schedule. The use of anti-
emetogenic regimens, this is a relatively straightforward dopaminergic and anticholinergic agents is very appro-
approach. In patients receiving highly emetogenic regi- priate in this setting. More important, however, is the
mens, however, it becomes more difficult. need to continually reassess the patient’s response to
The timing of the NK1 receptor antagonist dose or of therapy with each cycle. In some cases, severe or refrac-
the frequency of palonosetron dosing in these regimens tory nausea could be predicted, given a patient’s history
is poorly defined. Einhorn and colleagues evaluated the of poor tolerance of therapy, and adjustments could have
use of every 2-day palonosetron in patients receiving the been made to decrease the risk of nausea and vomiting.
highly emetogenic chemotherapeutic combination of Also, regular reevaluation of risk factors can help to

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 CLINICAL

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2006. www.merck.com/product/usa/pi_circulars/e/emend/emend_pi.pdf?WT.mc_id=
Author Disclosure Statement N02N3. Accessed June 21, 2012.
29. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist
Dr Rao and Dr Faso have reported no conflicts of interest. aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a
multinational, randomized, double-blind, placebo-controlled trial in patients receiv-
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Stakeholder Perspective on next page

Vol 5, No 4 l July 2012 www.AHDBonline.com l American Health & Drug Benefits l 239
 Chemotherapy-Induced Nausea and Vomiting

STAKEHOLDER PERSPECTIVE
Selecting Best Therapies for Control of Chemotherapy-Induced
Nausea and Vomiting
PROVIDERS/PAYERS: In a world of guidelines, guidelines are great in some cases, but value-based
algorithms, and literature searches, we often forget to considerations are essential to optimizing therapy in
focus on the patient. Nausea and vomiting are side our patients. Without consideration of the whole per-
effects that need to be evaluated differently from other son, the potential increased risk factors for CINV, and
effects related to chemotherapy in patients with can- other comorbid conditions, payers may approve reim-
cer. Thoughtful evaluation to determine the patho- bursement for whatever standard guidelines recom-
physiologic mechanisms that trigger nausea, as mend, but this will not necessarily be getting the best
described in the article by Dr Rao and Dr Faso, is key treatment for our patients. As providers, we have to
to selecting the optimal antinausea medications.1 make sure that we drive the decision for antiemetic
When evaluating chemotherapy-induced nausea and therapy based on patient-specific factors in addition
vomiting (CINV), we automatically think of serotonin to the chemotherapy itself.
in peripheral receptors and dopamine in the chemo- PATIENTS: Nausea and vomiting remain the side
receptor trigger zone as the primary culprits; however, effects of chemotherapy that patients with cancer fear
we must also consider any underlying causes that may the most. Almost every patient has known someone or
be contributing factors. had a family member who has “suffered” through
Direct interaction with and discussion of patients’ chemotherapy and has had horrendous issues with
past experiences with nausea, their perception of nausea, CINV. Patients report that they would rather be in
and their day-to-day lives affect the choice of antiemet- pain than have CINV, because many can work through
ics for patients with cancer. Neurologic or vision the pain, but nausea is completely debilitating. The
changes secondary to chemotherapy may contribute to best option is empowering patients to take control of
vestibular changes, indicating a need for anticholiner- their nausea through proper education, use of anti-
gics or antihistamines. Taste and smell changes second- emetics that are appropriate to their case, and through
ary to chemotherapy may require benzodiazepines or cor- continual follow-up and adjustment to their antiemetic
ticosteroids to help control nausea. The main point is regimens. Patients need to be given the opportunity to
that the patient must be evaluated beyond just the eme- sit down with a nurse or a pharmacist to reiterate the
togenic potential of the chemotherapy itself. As the counseling provided by their physicians. Our experi-
authors pointed out, clinical success is the first step in ence with this process has helped to improve monitor-
the value-based decision algorithm. ing and follow-up for patients with CINV.
Comorbid conditions also affect the success of these We must not only give patients the antiemetics
agents, and it is sometimes important to consider side they need, but we must also provide them with the
effects as intended benefits of some of these drugs. resources to be properly educated about these medica-
Steroids may cause agitation or weight gain, but some tions. Therefore, to incorporate value-based consider-
patients experience this as increased energy or mood ations for optimal therapy, it is necessary to ensure
boosts, which can be a dual benefit beyond the anti- that a cohesive multidisciplinary approach is provided
nausea component. Sedation is a common side effect to the patient.
with benzodiazepines, but patients with insomnia
(especially secondary to their corticosteroid use) may Robert Mancini, PharmD
realize dual benefit here as well. The key factors for Oncology Pharmacist
these patients are convenience and safety. St. Luke’s Mountain States Tumor Institute
A final consideration for healthcare providers is Boise, ID
the question of reimbursement, when the choice 1. Wood GJ, Shega JW, Lynch B, Von Roenn JH. Management of intractable nau-
“does not fit with the guidelines.” The fact is that sea and vomiting in patients at the end of life. JAMA. 2007;298:1196-1207.

240 l American Health & Drug Benefits l www.AHDBonline.com July 2012 l Vol 5, No 4