Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
Discussion This discussion is being updated to correspond with the
individual patient variability (e.g., age, sex, prior chemotherapy, history
newly updated algorithm. Last updated 04/12/10
of alcohol use).5, 6 Approximately 70% to 80% of all cancer patients receiving chemotherapy experience nausea and/or vomiting,7, 8
NCCN Categories of Evidence and Consensus
whereas 10% to 44% experience anticipatory nausea and/or
Category 1: The recommendation is based on high-level evidence
vomiting.9-12 Patients often experience more nausea than vomiting.13
(e.g. randomized controlled trials) and there is uniform NCCN
Pathophysiology of Emesis
Vomiting results from stimulation of a multistep reflex pathway
Category 2A: The recommendation is based on lower-level evidence
controlled by the brain.5 Vomiting is triggered by afferent impulses to
and there is uniform NCCN consensus.
the vomiting center (located in the medulla) from the chemoreceptor
Category 2B: The recommendation is based on lower-level evidence
trigger zone, pharynx and gastrointestinal (GI) tract (via vagal afferent
and there is nonuniform NCCN consensus (but no major
fibers), and cerebral cortex. Vomiting occurs when efferent impulses
are sent from the vomiting center to the salivation center, abdominal
muscles, respiratory center, and cranial nerves.14
Category 3: The recommendation is based on any level of evidence
but reflects major disagreement.
The chemoreceptor trigger zone, vomiting center, and GI tract have
All recommendations are category 2A unless otherwise noted.
many neurotransmitter receptors. Activation of these receptors by chemotherapeutic agents or their metabolites may be responsible for
Overview
chemotherapy-induced emesis. The principal neuroreceptors involved in the emetic response are the serotonin (5-hydroxytryptamine [5-HT3])
Chemotherapy-induced vomiting (emesis) and nausea can significantly
and dopamine receptors.15, 16 Other neuroreceptors involved in emesis
affect a patient's quality of life, leading to poor compliance with further
include acetylcholine, corticosteroid, histamine, cannabinoid, opiate,
chemotherapy treatment. In addition, nausea and vomiting can result in
and neurokinin-1 (NK-1) receptors, which are located in the vomiting
metabolic imbalances, degeneration of self-care and functional ability,
and vestibular centers of the brain.17
nutrient depletion, anorexia, decline of the patient's performance status and mental status, wound dehiscence, esophageal tears, and
Antiemetic agents can block different neuronal pathways, exert their
withdrawal from potentially useful or curative anticancer treatment.1-4
effects at different points during the course of emesis, or behave synergistically with other antiemetic agents to potentiate an antiemetic
The incidence and severity of nausea and/or vomiting in patients
effect. When used at a certain concentration, each antiemetic agent
receiving chemotherapy are affected by numerous factors, including:
predominantly blocks one receptor type. A final common pathway for
(1) the specific chemotherapeutic agents used; (2) dosage of the
emesis has yet to be identified. Therefore, no single agent can be
agents; (3) schedule and route of administration of the agents; and (4)
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
expected to provide complete protection from the various emetic
chemotherapy and, overall, have poorer emesis control than older
phases of chemotherapy.
patients.22 Breakthrough emesis refers to vomiting that occurs despite prophylactic treatment and/or requires "rescue" with antiemetic agents.
Types of Nausea and/or Vomiting
Refractory emesis refers to emesis that occurs during subsequent
Chemotherapy-Induced Nausea and/or Vomiting
treatment cycles when antiemetic prophylaxis and/or rescue have failed
Nausea and/or vomiting induced by chemotherapy is commonly
in earlier cycles.
classified as acute, delayed, anticipatory, breakthrough, or refractory.
Radiation-Induced Nausea and/or Vomiting
Acute-onset nausea and/or vomiting usually occurs within a few minutes to several hours after drug administration and commonly
Patients receiving whole body or upper abdominal radiation therapy
resolves within the first 24 hours. The intensity of acute-onset emesis
have the greatest likelihood of developing nausea and/or vomiting.23, 24
generally peaks after 5 to 6 hours. The occurrence of acute emesis is
The GI tract (specifically, the small intestine) contains rapidly dividing
influenced by the patient's age and gender (females and younger
cells that are particularly sensitive to radiation. In addition, the potential
patients [age < 50 years] are more prone to emesis), environment in
for nausea and/or vomiting increases with larger daily fractional doses
which chemotherapy is administered, whether the patient has a history
of radiotherapy, larger total doses, and larger amounts of irradiated
of chronic alcoholism (which decreases the incidence of emesis) or
tissue. Total body irradiation, when given before bone marrow
motion sickness, previous episodes of nausea and vomiting, dosage of
transplantation, also commonly induces nausea and/or vomiting.24, 25
the emetogenic agent, and efficacy of the antiemetic regimen.18, 19
Emetogenicity of Chemotherapy
Delayed-onset nausea and/or vomiting develops in patients more than
The frequency of chemotherapy-induced emesis depends primarily on
24 hours after chemotherapy administration.18, 19 It occurs commonly
the emetogenic potential of the specific chemotherapeutic agents used.
with the administration of cisplatin, carboplatin, cyclophosphamide,
Several classifications have been developed to define the
and/or doxorubicin. For cisplatin, emesis reaches its maximal intensity
emetogenicity of chemotherapy; however, none has been universally
48 to 72 hours after administration and can last 6 to 7 days.
accepted.14, 26-29
Anticipatory nausea and/or vomiting occurs before patients receive their
Hesketh and colleagues developed a classification of the acute
next chemotherapy treatment. Because it is a conditioned response,
emetogenicity of anticancer chemotherapeutic agents and developed
anticipatory emesis can occur only after a negative past experience
an algorithm to define the emetogenicity of combination
with chemotherapy. The incidence of anticipatory nausea and/or
chemotherapeutic regimens.30 The classification was updated by
vomiting ranges from 18% to 57%, and nausea is more common than
Grunberg and colleagues; it divides chemotherapeutic agents into 4
vomiting.20, 21 Younger patients may be more susceptible to anticipatory
levels according to the percentage of patients not receiving antiemetic
nausea and vomiting, because they generally receive more aggressive
prophylaxis who experience acute emesis.31 This classification, which is
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
updated each year with recently introduced drugs, is used in these
term (e.g., imatinib). Antiemetic agents can be administered by the oral,
NCCN practice guidelines. Panel members from all of the published
rectal, IV, intramuscular, or transdermal route. When compared with
antiemetic treatment guidelines met to prepare a single consensus
other routes of administration, oral formulations of antiemetic agents
document. Although this process is ongoing, the consensus guidelines
are equally effective, safe, more convenient, and less costly. For
have been published.32 NCCN guidelines currently outline treatment
patients unable to swallow or digest tablets because of emesis, IV
using 4 categories of emetogenic potential for intravenous (IV), which
antiemetics are required. In selected patients who are unable to
correspond to the Grunberg classification as follows:
swallow, transdermal antiemetics may be of value. Although studies may show drugs to be equally effective on a population basis, individual
High emetic risk—90% or more of patients experience acute emesis
patients may respond differently. Therefore, some drug options may be
Moderate emetic risk—30% to 90% of patients experience acute
based on a patient's individual experience.
Low emetic risk—10% to 30% of patients experience acute emesis
Serotonin (5-HT3) Receptor Antagonists
Minimal emetic risk—fewer than 10% of patients experience acute
The development of the 5-HT3–receptor antagonists (i.e., dolasetron
mesylate, granisetron, ondansetron, palonosetron) represents a significant advance in antiemetic therapy.33-35 All of these agents have
In addition, the NCCN guidelines attempt to define antiemetic regimens
been shown to be effective in controlling the acute nausea and/or
for particular chemotherapy drugs that cover the entire duration of time
vomiting associated with cancer chemotherapy.35-49
a patient is at risk for nausea and vomiting. Panel members were concerned that some patients may not receive adequate prophylaxis for
Palonosetron is a 5-HT3 antagonist with an approximately 100-fold
delayed emesis; therefore, the algorithms were revised for high and
higher binding affinity for the 5-HT3 receptor compared to the other
moderate emetogenic potential agents to incorporate a dosing schedule
serotonin antagonists (i.e., ondansetron, granisetron, and dolasetron). It
that covers both acute and delayed emesis into a single algorithm.
has a half-life of approximately 40 hours, which is significantly longer
Recently, NCCN panel members categorized the emetogenic potential
than other commercially available 5-HT3 antagonists.35 Initial studies in
of oral antineoplastic agents.
patients receiving moderately emetogenic chemotherapy showed that a single IV dose of palonosetron was comparable to a single IV dose of
Types of Antiemetic Therapies
dolasetron for the prevention of acute chemotherapy-induced nausea
In general, to provide maximal protection against chemotherapy-
and emesis; however, IV palonosetron was superior to dolasetron in
induced emesis, antiemetic therapy should be initiated before
preventing delayed emesis.50 The safety and side-effect profiles of
chemotherapy. The antiemetic therapy should also be continued for the
palonosetron were indistinguishable from the control 5-HT3 antagonists
same length of time as the duration of the emetic activity of the
(ondansetron and dolasetron) using data submitted to the Food and
chemotherapeutic agent being used. However, daily use of antiemetics
Drug Administration (FDA). Intravenous palonosetron is FDA approved
is not recommended for some therapeutic agents that are taken long
as a single dose on day 1; it is recommended (category 1) for acute
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
and delayed emesis prevention when using moderate emetic risk
However, IV palonosetron is effective for preventing both delayed and
acute emesis. A meta-analysis of randomized controlled trials found that adding a 5-HT3 antagonist to dexamethasone did not improve the
Intravenous palonosetron is superior to other 5-HT3 antagonists for
antiemetic effect of dexamethasone for preventing delayed emesis.73
preventing delayed nausea.51 Repeat dosing of palonosetron in the
Another study found that 5-HT3 antagonists (except palonosetron,
days after chemotherapy (i.e., days 2 or 3) is likely to be safe. However,
which was not studied) were not more effective than prochlorperazine
in the setting of multi-day chemotherapy, need for repeat dosing with
for preventing delayed emesis.13
palonosetron is not yet known (see "Managing Multi-day Emetogenic
Chemotherapy Regimens").
Neurokinin-1–Receptor Antagonist
Aprepitant selectively blocks the binding of substance P at the NK-1
Many of the 5-HT3 antagonists can be delivered orally or intravenously.
receptor in the central nervous system. Thus, aprepitant provides a
In addition, the FDA has approved the use of a granisetron transdermal
different and complementary mechanism of action to all other
system for chemotherapy-induced nausea and vomiting. The patch
commercially available antiemetics. Aprepitant has been shown to
containing 34.3 mg of granisetron is applied approximately 24 to 48
augment the antiemetic activity of the 5-HT3–receptor antagonists and
hours before the first dose of chemotherapy; the maximum duration of
the corticosteroid dexamethasone to inhibit both acute and delayed
the patch is 7 days. A phase III randomized study compared the patch
cisplatin-induced emesis. The FDA has approved the use of aprepitant
to oral granisetron in patients receiving either highly emetogenic or
for preventing emesis in patients receiving moderately emetogenic
moderately emetogenic chemotherapy. The patch proved non-inferior
chemotherapy. An IV version of aprepitant (fosaprepitant dimeglumine),
to repeat dosing of the oral antiemetic granisetron over 3 to 5 days.52, 53
which can be given on day 1 only, is also approved by the FDA. IV
Many clinical trials directly comparing ondansetron, granisetron,
fosaprepitant is given 30 minutes before chemotherapy on day 1
dolasetron mesylate, and palonosetron have been conducted. These
only, per the package insert.
trials have used various doses, routes, and schedules of
When combined with 5-HT3 antagonists and dexamethasone on day 1
administration.50, 54-71 Studies have demonstrated that the 5-HT3
before cisplatin-based highly emetogenic chemotherapy and continued
antagonists are equally effective and have mild, infrequent side effects.
orally along with dexamethasone on days 2 and 3 after chemotherapy,
A meta-analysis found no difference in efficacy between ondansetron,
aprepitant significantly improved control of acute and delayed
granisetron, and dolasetron mesylate.72 The addition of dexamethasone
chemotherapy-induced nausea and emesis.74, 75 The oral doses of
improves the efficacy of the antiemetic regimen containing 5-HT3
aprepitant are 125 mg on day 1 (before chemotherapy) and then 80 mg
on days 2 and 3 (after chemotherapy).76 There are no studies showing
Ondansetron, granisetron, and dolasetron are effective in preventing
efficacy or safety of chronic dosing with aprepitant. It is possible that
acute emesis but appear to be less effective for delayed emesis.
the drug-drug interaction profile may change with chronic dosing.
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
A randomized phase III study (866 patients) showed that an aprepitant
forms because of first-pass metabolism. Patients should not take
regimen is better than a standard regimen for preventing vomiting in
aprepitant with pimozide, terfenadine, astemizole, or cisapride; these
patients receiving moderately emetogenic chemotherapy (non-cisplatin
combinations are contraindicated, because they may cause "serious or
based) during 120 hours after initiation of chemotherapy (complete
life-threatening reactions" (see the aprepitant package insert).
response, 50.8% versus 42.5%, P=.015); however, 40% of patients (receiving either regimen) still had significant nausea.77, 78 The
Chemotherapeutic agents known to be metabolized by CYP3A4 include
aprepitant regimen included aprepitant, ondansetron, and
docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib,
dexamethasone; the standard regimen included ondansetron and
vinorelbine, vinblastine, and vincristine. In clinical trials, aprepitant was
dexamethasone. An analysis of 2 phase III randomized trials found that
used concurrently with etoposide, vinorelbine, or paclitaxel; although
an aprepitant regimen is useful for patients receiving moderately
chemotherapy doses were not adjusted for potential drug interactions in
emetogenic chemotherapy plus high-dose cisplatin.79
phase III trials, caution is urged when using any chemotherapeutic
agent that is metabolized by CYP3A4.
A meta-analysis (7 randomized controlled trials) in patients receiving highly emetogenic chemotherapy found that NK-1 receptor antagonists
Aprepitant has been shown to interact with several
used alone or with standard therapy for acute emesis were not better
nonchemotherapeutic drugs (including warfarin, dexamethasone,
than the control; however, for delayed emesis, NK-1 receptor
methylprednisolone, oral contraceptives). Again, these interactions are
antagonists were better than the control.80 A phase II study (58
more significant with orally administered forms of these drugs than with
patients) found that combining palonosetron, aprepitant, and
IV forms because of first-pass metabolism.
dexamethasone was useful for various chemotherapeutic regimens
Induction of warfarin metabolism by aprepitant may lead to clinically
(moderate to moderate-highly emetogenic); 78% of patients had a
significant reductions in INR (international normalized ratio) values,
complete response (no emetic episodes and no rescue medication).81 A
particularly for patients on therapeutic (as compared to prophylactic)
similar study in 40 patients with breast cancer also found that a single
warfarin regimens. These changes, although brief in duration, may
day regimen of palonosetron, aprepitant, and dexamethasone was
require increased patient monitoring.
effective; 76% of patients had a complete response.82
Aprepitant decreases the AUC for patients taking oral contraceptives;
Drug Interactions
thus, other methods of birth control should be used during treatment
Aprepitant is simultaneously a substrate, moderate inducer, and
with aprepitant and for 1 month after the last dose of aprepitant (see
moderate inhibitor of cytochrome P450 enzyme 3A4 (CYP3A4);
package insert).
aprepitant also induces CYP2C9.83 Thus, aprepitant can alter the metabolism of certain drugs and change their plasma concentrations
Certain drugs can affect the AUCs of aprepitant. Concomitant
(i.e., AUCs [area under the curve]). These interactions are more
administration with CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,
significant with orally administered forms of these drugs than with IV
erythromycin) may lead to increased aprepitant AUCs, whereas
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
concomitant administration with CYP3A4 inducers (e.g.,
Principles of Emesis Control
carbamazepine, rifampin, phenytoin) may lead to decreased levels of
These principles are discussed in the algorithm.
The goal is to prevent nausea and/or vomiting.
Other Non–5-HT3–Receptor Antagonist Antiemetics
The risk of emesis and nausea for persons receiving chemotherapy
Before the advent of the 5-HT3–receptor antagonists, the available
of high and moderate emetogenic potential lasts at least 3 days for
antiemetic agents included phenothiazines,84 substituted
high and 2 days for moderate after the last dose of chemotherapy.
benzamides,85, 86 antihistamines,87 butyrophenones,88 cortico-
Patients need to be protected throughout the full period of risk.
steroids,89-91 benzodiazepines,92, 93 and cannabinoids.94, 95 Most drugs
Oral and IV antiemetic formulations have equivalent efficacy.
used to prevent chemotherapy-induced emesis are classified as
The toxicity of the specific antiemetic(s) should be considered.
dopamine antagonists, serotonin antagonists, and other antagonists.
Antiemetic regimens should be chosen based on the drug with the
Combination antiemetic therapy is more effective than single-agent
highest emetic risk in the chemotherapy regimen, previous
therapy. Olanzapine (thiobenzodiazepine) was found to be effective for
experience with antiemetics, and patient-specific risk factors.
acute and delayed emesis in a phase II trial in patients (n = 30) who received cyclophosphamide, doxorubicin, and/or cisplatin;96, 97 other
In addition to emesis induced by chemotherapy, emesis in cancer
studies have also showed the value of olanzapine for delayed and
patients can also potentially be caused by:
refractory emesis and nausea.98-101 However, olanzapine should be
used with caution in elderly patients (see boxed warning/label indication
Partial or complete bowel obstruction
regarding death, type II diabetes, and hyperglycemia).102
Vestibular dysfunction Brain metastases
Treatment Issues
Electrolyte imbalance: hypercalcemia, hyperglycemia, hyponatremia
Selected issues that arose in the panel's deliberations on the guidelines
are discussed in the following sections. As new data about the use of
Concomitant drug treatments, including opiates
antiemetics in patients receiving chemotherapy become available,
Gastroparesis induced by a tumor or chemotherapy (i.e., vincristine)
clinicians should consider these data when caring for such patients,
or other causes (e.g., diabetes).
even if the information has not been included in the guidelines. In
Psychophysiologic factors, including anxiety and anticipatory nausea
contrast to other NCCN guidelines in which most of the
recommendations are category 2A, many of the recommendations for
For use of antiemetics for nausea and vomiting that is not related to
antiemetic management are classified as category 1, reflecting the
large number of randomized controlled trials that have focused on
antiemetic management.
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
For multidrug regimens, select antiemetic therapy based on drug with
with or without either an H2 blocker or a proton pump inhibitor (category
the highest emetic risk.30, 31
1 for the combined regimen);24, 25, 74 note that the regimen and doses are often modified on days 2 to 4 after chemotherapy.
Prevention of Acute Emesis
To prevent acute emesis, antiemetic therapy should start before the
A recent randomized trial suggested that palonosetron is preferred for
administration of chemotherapy and then should cover the first 24
high emetic risk chemotherapy in combination with dexamethasone.103
hours. For highly emetogenic IV drugs, the antiemetic regimens are
However, this trial has been criticized because: 1) the control arm was
described in the algorithm. For moderately emetogenic IV drugs, the
not adequately dosed; thus, the trial "stacked the deck" in favor of
regimens are described in the algorithm. For low and minimally
palonosetron; 2) a larger non-FDA-approved dose of palonosetron was
emetogenic IV drugs, the regimens are described in the algorithm.
used; and 3) aprepitant was not used in this study. Therefore, the
Emesis prevention for oral chemotherapeutic agents is described in the
NCCN panel does not believe that palonosetron is preferred over the
algorithm. This section discusses prechemotherapy and
other 5-HT3 antagonists for high emetic risk chemotherapy.
postchemotherapy emesis prevention rather than primary treatment.
A Canadian meta-analysis suggests that it is not cost-effective to use
5-HT3 antagonists (i.e., ondansetron) on days 2 to 4 to prevent delayed
The guidelines specify different prophylactic antiemetic regimens for
emesis; however, ondansetron (when used alone) did protect against
cancer patients receiving chemotherapy of different emetogenic
delayed emesis in this meta-analysis.104 Palonosetron was not
potential (i.e., high, moderate, low, minimal). Prophylactic antiemetics
assessed in these studies. The NCCN panel recommends the use of
should be administered before chemotherapy. The recommendations
5-HT3 antagonists as one of several options to prevent delayed emesis
for prophylactic antiemetic treatment include drug dosages. The
for moderately emetogenic agents.
guidelines reflect accumulating experience with the 5-HT3 antagonists,
The antiemetic regimen for moderately emetogenic IV drugs on day 1
demonstrating their effectiveness in a range of doses. Unless indicated,
includes dexamethasone and a 5-HT3 antagonist with or without
the order of listed antiemetics in the algorithm does not reflect
lorazepam and/or either an H2 blocker or a proton pump inhibitor.5, 78
Aprepitant (or fosaprepitant) should be added (to dexamethasone and a
Highly emetogenic IV drugs include carmustine > 250 mg/m2, cisplatin
5-HT3 antagonist) for select patients receiving other chemotherapies of
at 50 mg/m2 or more, cyclophosphamide > 1500 mg/m2, dacarbazine,
moderate emetic risk (e.g., carboplatin, cisplatin, doxorubicin,
mechlorethamine, streptozocin, or anthracycline plus
epirubicin, ifosfamide, irinotecan, or methotrexate), because these
cyclophosphamide (AC) combinations (doxorubicin or epirubicin with
agents are more emetogenic than the other moderately emetogenic
cyclophosphamide). The antiemetic regimen for these highly
agents.25, 30 Any one of the 5-HT3 antagonists can be used, because
emetogenic drugs on day 1 includes aprepitant (or fosaprepitant),
they are all category 1 for day 1. Note that IV fosaprepitant may be
dexamethasone, and a 5-HT3 antagonist with or without lorazepam and
substituted for oral aprepitant on day 1 only.
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
The antiemetic regimen for low emetogenic IV drugs includes
Postchemotherapy/Delayed Emesis Prevention
non-5-HT3 antagonists, such as dexamethasone, prochlorperazine, or
The best management for delayed emesis is prevention.105 For
metoclopramide, with or without lorazepam and/or either an H2 blocker
chemotherapy involving agents with high emetogenic potential, the
or a proton pump inhibitor. When using prochlorperazine or
prophylactic treatment (i.e., dexamethasone and aprepitant) is
metoclopramide, patients should be monitored for dystonic reactions.
continued through the period when delayed emesis may occur. Using
Diphenhydramine (25-50 mg PO or IV either every 4 or every 6 hours)
this strategy, prophylaxis continues for 2 to 4 days after completion of a
can be used for dystonic reactions.
chemotherapy cycle. However, 5-HT3 antagonists are given on day 1
For IV regimens with high emetogenic potential, aprepitant is used at a oral dosage of 125 mg on day 1 and then 80 mg on days 2 and 3.
For drugs with moderate emetogenic potential, postchemotherapy
When given with aprepitant, dexamethasone is used at a dosage of 12
prevention depends on what antiemetics were used before
mg on day 1; the dose can be oral or IV. All four 5-HT3–receptor
chemotherapy. For example, palonosetron (category 1) is only
antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron)
administered on day 1.54 If aprepitant or fosaprepitant was used on day
are considered to have similar effectiveness for control of acute emesis.
1, then aprepitant is continued on days 2 and 3.
If appropriate, lorazepam (0.5-2 mg either every 4 or every 6 hours on days 1-4; either oral, IV, or sublingual) may be used with each of these
Note that the NCCN antiemetic regimens differ on days 2 to 3.24, 25, 105
regimens (i.e., high, moderate, or low).
There are 4 possible regimens on days 2-3 (lorazepam and/or either an H2 blocker or a proton pump inhibitor may be added to each of these
The emetogenic potential of oral chemotherapeutic agents is shown in
regimens) including: 1) aprepitant and dexamethasone; 2) aprepitant;
the algorithm. Antiemetic prophylaxis is recommended for the following
3) dexamethasone; or 4) 5-HT3 antagonist, such as ondansetron,
oral agents: altretamine, busulfan (4 mg/d or more), cyclophosphamide
granisetron, or dolasetron.105 It is important to note that the doses of
(100 mg/m2/day or more), estramustine, etoposide, lomustine (single
both aprepitant (80 mg PO) and dexamethasone (8 mg PO or IV) are
day), procarbazine, and temozolomide (75 mg/m2/day or more).
decreased when used on days 2-3 (when compared with the doses
Prophylaxis uses oral 5-HT3 antagonists (such as dolasetron,
given on day 1). Note that palonosetron is not given on days 2-3.
granisetron, or ondansetron) with or without lorazepam and/or either an H2 blocker or a proton pump inhibitor. If routine prophylaxis is not
The NCCN, MASCC (Multinational Association of Supportive Care in
recommended, then either metoclopramide or prochlorperazine may be
Cancer), and ASCO (American Society of Clinical Oncology) guidelines
given before chemotherapy is started and then on an as needed basis
all recommend using aprepitant to prevent delayed nausea and/or
only (i.e., PRN) with or without lorazepam and/or either an H2 blocker
vomiting when giving AC regimens.24, 25 Several randomized trials have
or a proton pump inhibitor.
shown that dexamethasone is efficacious for preventing delayed emesis; however, only one trial found that use of a 5-HT3 antagonist is effective.105 The MASCC and NCCN (but not ASCO) guidelines also
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
recommend using dexamethasone for preventing delayed emesis when
chemotherapy, the antiemetic regimen (both the day 1 and
giving AC regimens.105
postchemotherapeutic) that did not protect the patient during the present cycle should be assessed and alternatives should be
Breakthrough Treatment
considered. Consider using antacid therapy (e.g., proton pump
Breakthrough emesis presents a difficult situation, because refractory
inhibitors, H2 blockers) if patients have dyspepsia, because patients
ongoing nausea and/or vomiting is often challenging to reverse.
sometimes have difficulty discriminating heartburn from nausea.
Generally, it is much easier to prevent nausea and/or vomiting than to treat it. Thus, routine around-the-clock administration of antiemetics
Radiation-Induced Nausea and/or Vomiting
should be strongly considered to prevent emesis, rather than PRN (as
Prophylaxis for radiation-induced nausea and/or vomiting is based on
required) dosing. The general principle of breakthrough treatment is to
the site of radiation and whether it is combined with chemotherapy.109
give an additional agent as needed from a different drug class.24
When radiation is combined with chemotherapy, prophylaxis is dictated
However, no one treatment is better than another for managing
by the emetogenic potential of the chemotherapy regimen.
breakthrough emesis.106 Some patients may require several agents using different mechanisms of action. The oral route is not likely to be
Radiation to the upper abdomen may be treated with oral ondansetron
feasible because of ongoing vomiting; therefore, rectal or IV therapy is
(8 mg 2 times daily), with or without oral dexamethasone, based on the
often required. Nasal sprays (e.g., metoclopramide) might be useful for
results of a randomized study comparing oral ondansetron with placebo
treatment of breakthrough emesis, because they provide acute delivery
in patients receiving daily fractionated radiotherapy including the
of agents.107, 108 Multiple concurrent agents, perhaps in alternating
abdomen. In this study, 67% of patients given ondansetron had
schedules or by alternating routes, may be necessary.
complete control of emesis compared with 45% of patients who received placebo.110 A study showed that the addition of oral
Dopamine antagonists (e.g., metoclopramide), haloperidol,
dexamethasone (4 mg daily) to the ondansetron regimen decreases
corticosteroids, and agents such as lorazepam may be required.
emesis and nausea, although the effect is modest.111 Another option is
Nabilone (which is a cannabinoid) is approved by the FDA for nausea
oral granisetron (2 mg every day) with or without oral dexamethasone.
and vomiting in patients who have not responded to conventional antiemetic agents. Adequate hydration or fluid repletion should be
Total body irradiation may be treated with either ondansetron (8 mg 2 to
ensured, and any possible electrolyte abnormalities should be
3 times daily) or granisetron; either agent can be given with or without
assessed and corrected. Before administering the next cycle of
oral dexamethasone (2 mg 3 times daily).111 The dose of granisetron is
chemotherapy, the patient should be reassessed with attention to
either 2 mg oral every day or 3 mg IV every day112, 113 (category 2B
various possible nonchemotherapy-related reasons for breakthrough
recommendation, because this dose of granisetron is higher than the
emesis with the current cycle (i.e., brain metastases, electrolyte
dose typically used). No prophylaxis is recommended for patients
abnormalities, tumor infiltration of the bowel or other GI abnormality,
receiving irradiation to other sites.
and other comorbidities. In addition, before the next cycle of
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
Treatment of breakthrough radiation-induced emesis is similar to
difficult to recommend a specific antiemetic regimen for each day,
chemotherapy-induced emesis. Patients who do not receive primary
especially because acute and delayed emesis may overlap after the
prophylaxis and experience breakthrough nausea and/or vomiting may
initial day of chemotherapy until the last day of chemotherapy. The
be treated with ondansetron, similar to primary prophylaxis.
period of risk for delayed emesis after chemotherapy administration has concluded also depends on the specific regimen and the emetogenic
Anticipatory Nausea and/or Vomiting
potential of the last chemotherapy agent administered in the regimen.
The most effective way to treat anticipatory nausea and/or vomiting is
For multi-drug regimens, antiemetic therapy should be selected based
to prevent it by using optimal antiemetic therapy during every cycle of
on the drug with the highest emetic risk. General principles for
treatment.24, 114 Behavioral therapy has been used in patients with
managing multi-day emetogenic chemotherapy regimens
anticipatory nausea and/or vomiting.115-120 Systematic desensitization
recommended by the panel are described in the algorithm.
may also be helpful.116 Hypnosis with guided imagery is another behavioral technique that has shown some success in treating this
Dexamethasone should be administered once daily either orally or
intravenously for every day of moderately or highly emetogenic chemotherapy and for 2-3 days after chemotherapy for regimens that
The antianxiety agents, lorazepam and alprazolam, have been
are likely to cause significant delayed emesis. However,
combined with antiemetics for anticipatory nausea and/or
dexamethasone should not be added when the chemotherapy regimen
vomiting.114,121, 122 The usual starting dose of alprazolam for anxiety is
already includes a corticosteroid.
0.25 to 0.5 mg orally
A 5-HT3 receptor antagonist should be administered each day before
3 times daily, beginning on the night before treatment. In elderly
the first dose of moderately or highly-emetogenic chemotherapy.
patients, patients with debilitating disease, and patients with advanced
Intravenous palonosetron may be used before the start of a 3-day
liver disease, the usual starting dose of alprazolam is 0.25 mg orally 2
chemotherapy regimen instead of multiple daily doses of oral or
or 3 times daily for treatment of anxiety. This dose may be gradually
intravenous 5-HT3 receptor antagonists.127, 128 Repeat dosing of
increased if needed. Note that the elderly are especially sensitive to the
palonosetron 0.25 mg IV is likely to be safe, based upon the dose
effects of benzodiazepines. The dose should be gradually reduced
ranging phase II trial where up to 30 times the FDA-approved dose (90
when decreasing or discontinuing alprazolam therapy.
mcg/kg) was administered and the 3 phase III trials that evaluated palonosetron 0.75 mg as a single fixed dose.50, 54, 129, 130 Compared to
Managing Multi-Day Emetogenic Chemotherapy
the approved dose of palonosetron of 0.25 mg, these higher doses
Regimens
were not associated with significantly different grades or durations of
Patients receiving multi-day chemotherapy are at risk for both acute
adverse events. Of note, patients receiving highly emetogenic multi-day
and delayed nausea and vomiting based on the emetogenic potential of
cisplatin-based chemotherapy for testicular cancer received multiple-
the individual chemotherapy agents and their sequence.24, 75, 123-126 It is
day dosing of palonosetron and dexamethasone, which prevented
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-10
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
nausea and emesis.131 In terms of efficacy, need for repeat dosing with palonosetron, either daily or less frequently, in the setting of multi-day
chemotherapy is not yet known.
Aprepitant may be used for multi-day chemotherapy regimens likely to be highly emetogenic and associated with significant risk for delayed nausea and emesis. As per the labeled indication, aprepitant should be administered 125 mg orally 1 hour prior to chemotherapy on day 1, along with a 5-HT3 receptor antagonist and dexamethasone. Aprepitant 80 mg should be administered daily on days 2 and 3 after the start of chemotherapy along with dexamethasone.75 Repeated dosing of aprepitant over multiple cycles is tolerated.75 Based on phase II data, aprepitant 80 mg may be safely administered on days 4 and 5 after chemotherapy.76 It is not yet known if dosing aprepitant after day 3 improves control of nausea or emesis in this clinical setting. Note that fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant
(125 mg) on day 1 only.
Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-11
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
References
9. Nesse RM, Carli T, Curtis GC, Kleinman PD. Pretreatment nausea in cancer chemotherapy: a conditioned response? Psychosom Med
1. Laszlo J. Emesis as limiting toxicity in cancer chemotherapy. In:
1980;42:33-36. Available at:
Laszlo J, ed. Antiemetics and Cancer Chemotherapy. Baltimore,
Maryland: Williams & Wilkins; 1983:1-5.
10. Wilcox PM, Fetting JH, Nettesheim KM, Abeloff MD. Anticipatory
2. Ingle RJ, Burish TG, Wallston KA. Conditionability of cancer
vomiting in women receiving cyclophosphamide, methotrexate, and 5-
chemotherapy patients. Oncol Nurs Forum 1984;11:97-9102. Available
FU (CMF) adjuvant chemotherapy for breast carcinoma. Cancer Treat
at: http://www.ncbi.nlm.nih.gov/pubmed/6566342.
Rep 1982;66:1601-1604. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7049385.
3. Mitchell EP. Gastrointestinal toxicity of chemotherapeutic agents. Semin Oncol 1992;19:566-579. Available at:
11. Carey MP, Burish TG. Anxiety as a predictor of behavioral therapy
outcome for cancer chemotherapy patients. J Consult Clin Psychol 1985;53:860-865. Available at:
4. Richardson JL, Marks G, Levine A. The influence of symptoms of
disease and side effects of treatment on compliance with cancer therapy. J Clin Oncol 1988;6:1746-1752. Available at:
12. Morrow GR, Lindke J, Black PM. Predicting development of
anticipatory nausea in cancer patients: prospective examination of eight clinical characteristics. J Pain Symptom Manage 1991;6:215-223.
5. Herrstedt J. Antiemetics: an update and the MASCC guidelines
Available at: http://www.ncbi.nlm.nih.gov/pubmed/2030296.
applied in clinical practice. Nat Clin Pract Oncol 2008;5:32-43. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18097455.
13. Hickok JT, Roscoe JA, Morrow GR, et al. 5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed
6. Hesketh PJ, Grunberg SM, Herrstedt J, et al. Combined data from
nausea caused by doxorubicin: a URCC CCOP randomised controlled
two phase III trials of the NK1 antagonist aprepitant plus a 5HT 3
trial. Lancet Oncol 2005;6:765-772. Available at:
antagonist and a corticosteroid for prevention of chemotherapy-induced
nausea and vomiting: effect of gender on treatment response. Support Care Cancer 2006;14:354-360. Available at:
14. Craig JB, Powell BL. The management of nausea and vomiting in
clinical oncology. Am J Med Sci 1987;293:34-44. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3544842.
7. Morran C, Smith DC, Anderson DA, McArdle CS. Incidence of nausea and vomiting with cytotoxic chemotherapy: a prospective
15. Borison HL, Wang SC. Physiology and pharmacology of vomiting.
randomised trial of antiemetics. Br Med J 1979;1:1323-1324. Available
Pharmacol Rev 1953;5:193-230. Available at:
at: http://www.ncbi.nlm.nih.gov/pubmed/445053.
8. Jenns K. Importance of nausea. Cancer Nurs 1994;17:488-493.
16. Seigel LJ, Longo DL. The control of chemotherapy-induced emesis.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/7820827.
Ann Intern Med 1981;95:352-359. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7023313.
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-1
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
17. Dodds LJ. The control of cancer chemotherapy-induced nausea
25. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of
and vomiting. J Clin Hosp Pharm 1985;10:143-166. Available at:
Clinical Oncology guideline for antiemetics in oncology: update 2006. J
Clin Oncol 2006;24:2932-2947. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16717289.
18. Kris MG, Gralla RJ, Clark RA, et al. Incidence, course, and severity of delayed nausea and vomiting following the administration of high-
26. Laszlo J. Treatment of nausea and vomiting caused by cancer
dose cisplatin. J Clin Oncol 1985;3:1379-1384. Available at:
chemotherapy. Cancer Treat Rev 1982;9 Suppl B:3-9. Available at:
19. Roila F, Boschetti E, Tonato M, et al. Predictive factors of delayed
27. Strum SB, McDermed JE, Pileggi J, et al. Intravenous
emesis in cisplatin-treated patients and antiemetic activity and
metoclopramide: prevention of chemotherapy-induced nausea and
tolerability of metoclopramide or dexamethasone. A randomized single-
vomiting. A preliminary evaluation. Cancer 1984;53:1432-1439.
blind study. Am J Clin Oncol 1991;14:238-242. Available at:
Available at: http://www.ncbi.nlm.nih.gov/pubmed/6692333.
28. Lindley CM, Bernard S, Fields SM. Incidence and duration of
20. Moher D, Arthur AZ, Pater JL. Anticipatory nausea and/or vomiting.
chemotherapy-induced nausea and vomiting in the outpatient oncology
Cancer Treat Rev 1984;11:257-264. Available at:
population. J Clin Oncol 1989;7:1142-1149. Available at:
21. Jacobsen PB, Redd WH. The development and management of
29. Aapro M. Methodological issues in antiemetic studies. Invest New
chemotherapy-related anticipatory nausea and vomiting. Cancer Invest
Drugs 1993;11:243-253. Available at:
1988;6:329-336. Available at:
30. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying
22. Morrow GR. Clinical characteristics associated with the
the acute emetogenicity of cancer chemotherapy. J Clin Oncol
development of anticipatory nausea and vomiting in cancer patients
1997;15:103-109. Available at:
undergoing chemotherapy treatment. J Clin Oncol 1984;2:1170-1176.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/6491699.
31. Grunberg SM, Osoba D, Hesketh PJ, et al. Evaluation of new
23. Harding R, Young R, Anno G. Radiotherapy-induced emesis. In:
antiemetic agents and definition of antineoplastic agent emetogenicity--
Andrews P, Sanger G, eds. Emesis in Anti-Cancer Therapy. London:
an update. Support Care Cancer 2005;13:80-84. Available at:
Chapman & Hall Medical; 1993:163-178.
24. Roila F, Hesketh PJ, Herrstedt J. Prevention of chemotherapy- and
32. Koeller JM, Aapro MS, Gralla RJ, et al. Antiemetic guidelines:
radiotherapy-induced emesis: results of the 2004 Perugia International
creating a more practical treatment approach. Support Care Cancer
Antiemetic Consensus Conference. Ann Oncol 2006;17:20-28.
2002;10:519-522. Available at:
Available at: http://www.ncbi.nlm.nih.gov/pubmed/16314401.
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-2
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
33. Hesketh PJ, Gandara DR. Serotonin antagonists: a new class of
40. Marty M. A comparative study of the use of granisetron, a selective
antiemetic agents. J Natl Cancer Inst 1991;83:613-620. Available at:
5-HT3 antagonist, versus a standard anti-emetic regimen of
chlorpromazine plus dexamethasone in the treatment of cytostatic-induced emesis. The Granisetron Study Group. Eur J Cancer 1990;26
34. Andrews PL, Bhandari P, Davey PT, et al. Are all 5-HT3 receptor
Suppl 1:S28-32. Available at:
antagonists the same? Eur J Cancer 1992;28A Suppl 1:2-6. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/1320915.
41. Marty M, Pouillart P, Scholl S, et al. Comparison of the 5-
35. Grunberg SM, Koeller JM. Palonosetron: a unique 5-HT3-receptor
hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F)
antagonist for the prevention of chemotherapy-induced emesis. Expert
with high-dose metoclopramide in the control of cisplatin-induced
Opin Pharmacother 2003;4:2297-2303. Available at:
emesis. N Engl J Med 1990;322:816-821. Available at:
36. Grunberg SM, Stevenson LL, Russell CA, McDermed JE. Dose
42. Soukop M. A comparison of two dose levels of granisetron in
ranging phase I study of the serotonin antagonist GR38032F for
patients receiving high-dose cisplatin. The Granisetron Study Group.
prevention of cisplatin-induced nausea and vomiting. J Clin Oncol
Eur J Cancer 1990;26 Suppl 1:S15-19. Available at:
1989;7:1137-1141. Available at:
43. Roila F, Tonato M, Cognetti F, et al. Prevention of cisplatin-induced
37. Chevallier B. Efficacy and safety of granisetron compared with high-
emesis: a double-blind multicenter randomized crossover study
dose metoclopramide plus dexamethasone in patients receiving high-
comparing ondansetron and ondansetron plus dexamethasone. J Clin
dose cisplatin in a single-blind study. The Granisetron Study Group. Eur
Oncol 1991;9:675-678. Available at:
J Cancer 1990;26 Suppl 1:S33-36. Available at:
44. Fraschini G. Antiemetic activity of ondansetron in cancer patients
38. Cupissol DR, Serrou B, Caubel M. The efficacy of granisetron as a
receiving non-cisplatin chemotherapy. Semin Oncol 1992;19:41-47.
prophylactic anti-emetic and intervention agent in high-dose cisplatin-
Available at: http://www.ncbi.nlm.nih.gov/pubmed/1387249.
induced emesis. Eur J Cancer 1990;26 Suppl 1:23-27. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2169782.
45. Kamanabrou D. Intravenous granisetron--establishing the optimal dose. The Granisetron Study Group. Eur J Cancer 1992;28A Suppl 1:6-
39. De Mulder PH, Seynaeve C, Vermorken JB, et al. Ondansetron
11. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1320919.
compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter,
46. Sledge GW, Einhorn L, Nagy C, House K. Phase III double-blind
randomized, double-blind, crossover study. Ann Intern Med
comparison of intravenous ondansetron and metoclopramide as
1990;113:834-840. Available at:
antiemetic therapy for patients receiving multiple-day cisplatin-based
chemotherapy. Cancer 1992;70:2524-2528. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1423181.
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-3
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
47. Chevallier B. The control of acute cisplatin-induced emesis--a
induced nausea and vomiting. J Oncol Pharm Pract 2009;15:223-231.
comparative study of granisetron and a combination regimen of high-
Available at: http://www.ncbi.nlm.nih.gov/pubmed/19304880.
dose metoclopramide and dexamethasone. Granisetron Study Group. Br J Cancer 1993;68:176-180. Available at:
54. Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron
improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-
48. Navari RM, Kaplan HG, Gralla RJ, et al. Efficacy and safety of
blind randomized phase III trial comparing single doses of palonosetron
granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in
with ondansetron. Ann Oncol 2003;14:1570-1577. Available at:
the prevention of nausea and vomiting induced by high-dose cisplatin. J
Clin Oncol 1994;12:2204-2210. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7931490.
55. Bonneterre J, Hecquet B. Granisetron (IV) compared with ondansetron (IV plus oral) in the prevention of nausea and vomiting
49. Riviere A. Dose finding study of granisetron in patients receiving
induced by moderately-emetogenic chemotherapy. A cross-over study.
high-dose cisplatin chemotherapy. The Granisetron Study Group. Br J
Bull Cancer 1995;82:1038-1043. Available at:
Cancer 1994;69:967-971. Available at:
56. Jantunen IT, Kataja VV, Johansson RT. Ondansetron and
50. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved
tropisetron with dexamethasone in the prophylaxis of acute vomiting
prevention of moderately emetogenic chemotherapy-induced nausea
induced by non-cisplatin-containing chemotherapy. Acta Oncol
and vomiting with palonosetron, a pharmacologically novel 5-HT3
1992;31:573-575. Available at:
receptor antagonist: results of a phase III, single-dose trial versus
dolasetron. Cancer 2003;98:2473-2482. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14635083.
57. Jantunen IT, Muhonen TT, Kataja VV, et al. 5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately
51. Aapro MS. Palonosetron as an anti-emetic and anti-nausea agent in
emetogenic chemotherapy--a randomised study. Eur J Cancer
oncology. Ther Clin Risk Manag 2007;3:1009-1020. Available at:
1993;29A:1669-1672. Available at:
52. Grunberg S, Gabrial N, Clark G. Phase III trial of transdermal
58. Martoni A, Angelelli B, Guaraldi M, et al. An open randomised
granisetron patch (Sancuso) compared to oral granisetron (OG) for
cross-over study on granisetron versus ondansetron in the prevention
chemotherapy-induced nausea and vomiting (CINV) after multi-day
of acute emesis induced by moderate dose cisplatin-containing
moderately emetogenic (MEC) or highly emetogenic (HEC)
regimens. Eur J Cancer 1996;32A:82-85. Available at:
chemotherapy [abstract P-18] [abstract]. Presented at the
MASCC/ISOO 20th Anniversary International Symposium Supportive Care in Cancer; St. Gallen, Switzerland. 687.
59. Campora E, Simoni C, Rosso R. [Tropisetron versus ondansetron in the prevention and control of emesis in patients undergoing
53. Howell J, Smeets J, Drenth HJ, Gill D. Pharmacokinetics of a
chemotherapy with FAC/FEC for metastatic or surgically treated breast
granisetron transdermal system for the treatment of chemotherapy-
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-4
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
carcinoma]. Minerva Med 1994;85:25-31. Available at:
66. Navari R, Gandara D, Hesketh P, et al. Comparative clinical trial of
granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol 1995;13:1242-
60. Gebbia V, Cannata G, Testa A, et al. Ondansetron versus
1248. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7738628.
granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial. Cancer
67. Stewart A, McQuade B, Cronje JD, et al. Ondansetron compared
1994;74:1945-1952. Available at:
with granisetron in the prophylaxis of cyclophosphamide-induced
emesis in out-patients: a multicentre, double-blind, double-dummy, randomised, parallel-group study. Emesis Study Group for
61. Mantovani G, Maccio A, Bianchi A, et al. Comparison of
Ondansetron and Granisetron in Breast Cancer Patients. Oncology
granisetron, ondansetron, and tropisetron in the prophylaxis of acute
1995;52:202-210. Available at:
nausea and vomiting induced by cisplatin for the treatment of head and
neck cancer: a randomized controlled trial. Cancer 1996;77:941-948. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8608488.
68. Audhuy B, Cappelaere P, Martin M, et al. A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous
62. Noble A, Bremer K, Goedhals L, et al. A double-blind, randomised,
doses of dolasetron mesilate and granisetron in patients receiving high
crossover comparison of granisetron and ondansetron in 5-day
dose cisplatin chemotherapy. Eur J Cancer 1996;32A:807-813.
fractionated chemotherapy: assessment of efficacy, safety and patient
Available at: http://www.ncbi.nlm.nih.gov/pubmed/9081358.
preference. The Granisetron Study Group. Eur J Cancer 1994;30A:1083-1088. Available at:
69. Fauser AA, Duclos B, Chemaissani A, et al. Therapeutic
equivalence of single oral doses of dolasetron mesilate and multiple doses of ondansetron for the prevention of emesis after moderately
63. Ruff P, Paska W, Goedhals L, et al. Ondansetron compared with
emetogenic chemotherapy. European Dolasetron Comparative Study
granisetron in the prophylaxis of cisplatin-induced acute emesis: a
Group. Eur J Cancer 1996;32A:1523-1529. Available at:
multicentre double-blind, randomised, parallel-group study. The
Ondansetron and Granisetron Emesis Study Group. Oncology 1994;51:113-118. Available at:
70. Hesketh P, Navari R, Grote T, et al. Double-blind, randomized
comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute
64. Ondansetron versus granisetron, both combined with
cisplatin-induced emesis in patients with cancer. Dolasetron
dexamethasone, in the prevention of cisplatin-induced emesis. Italian
Comparative Chemotherapy-induced Emesis Prevention Group. J Clin
Group of Antiemetic Research. Ann Oncol 1995;6:805-810. Available
Oncol 1996;14:2242-2249. Available at:
at: http://www.ncbi.nlm.nih.gov/pubmed/8589019.
65. Marty M, Kleisbauer JP, Fournel P, et al. Is Navoban (tropisetron)
71. Lofters WS, Pater JL, Zee B, et al. Phase III double-blind
as effective as Zofran (ondansetron) in cisplatin-induced emesis? The
comparison of dolasetron mesylate and ondansetron and an evaluation
French Navoban Study Group. Anticancer Drugs 1995;6 Suppl 1:15-21.
of the additive role of dexamethasone in the prevention of acute and
Available at: http://www.ncbi.nlm.nih.gov/pubmed/7749165.
delayed nausea and vomiting due to moderately emetogenic
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-5
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
chemotherapy. J Clin Oncol 1997;15:2966-2973. Available at:
72. Jordan K, Hinke A, Grothey A, et al. A meta-analysis comparing the
78. Warr DG, Hesketh PJ, Gralla RJ, et al. Efficacy and tolerability of
efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-
aprepitant for the prevention of chemotherapy-induced nausea and
induced emesis. Support Care Cancer 2007;15:1023-1033. Available
vomiting in patients with breast cancer after moderately emetogenic
at: http://www.ncbi.nlm.nih.gov/pubmed/17205281.
chemotherapy. J Clin Oncol 2005;23:2822-2830. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15837996.
73. Huang JQ, Zheng GF, Deuson R, et al. Do 5-hydroxytryptamine3 receptor antagonists (5-HT3) improve the antiemetic effect of
79. Gralla RJ, Warr DG, Carides AD, et al. Effect of aprepitant on
dexamethasone for preventing delayed chemotherapy-induced nausea
antiemetic protection in patients receiving moderately emetogenic
and vomiting (CINV)? A meta-analysis of randomized controlled trials
chemotherapy plus high-dose cisplatin: Analysis of combined data from
[abstract]. J Clin Oncol 2004;22 (Suppl 14): Abstract 6037. Available at:
2 phase III randomized clinical trials [abstract]. J Clin Oncol 2004;22
(Suppl 14):Abstract 8137. Available at: http://meeting.ascopubs.org/cgi/content/abstract/22/14_suppl/8137.
74. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced
80. Tremont-Lukats IW, Gonzalez-Barboteo J, Bruera E, Brescia FJ.
nausea and vomiting: a multinational, randomized, double-blind,
Meta-analysis of neurokinin-1 receptor antagonists (NK-1 RA) for
placebo-controlled trial in patients receiving high-dose cisplatin--the
chemotherapy-induced nausea and vomiting (CINV) [abstract]. J Clin
Aprepitant Protocol 052 Study Group. J Clin Oncol 2003;21:4112-4119.
Oncol 2004;22 (Suppl 14):Abstract 8047. Available at:
Available at: http://www.ncbi.nlm.nih.gov/pubmed/14559886.
75. de Wit R, Herrstedt J, Rapoport B, et al. The oral NK(1) antagonist,
81. Grote T, Hajdenberg J, Cartmell A, et al. Combination therapy for
aprepitant, given with standard antiemetics provides protection against
chemotherapy-induced nausea and vomiting in patients receiving
nausea and vomiting over multiple cycles of cisplatin-based
moderately emetogenic chemotherapy: palonosetron, dexamethasone,
chemotherapy: a combined analysis of two randomised, placebo-
and aprepitant. J Support Oncol 2006;4:403-408. Available at:
controlled phase III clinical trials. Eur J Cancer 2004;40:403-410.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/14746859.
82. Grunberg SM, Dugan M, Muss H, et al. Effectiveness of a single-
76. Chawla SP, Grunberg SM, Gralla RJ, et al. Establishing the dose of
day three-drug regimen of dexamethasone, palonosetron, and
the oral NK1 antagonist aprepitant for the prevention of chemotherapy-
aprepitant for the prevention of acute and delayed nausea and vomiting
induced nausea and vomiting. Cancer 2003;97:2290-2300. Available at:
caused by moderately emetogenic chemotherapy. Support Care
Cancer 2009;17:589-594. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19037667.
77. Warr DG, Eisenberg P, Hesketh PJ, et al. Effect of aprepitant for the prevention of nausea and vomiting after one cycle of moderately
83. Shadle CR, Lee Y, Majumdar AK, et al. Evaluation of potential
emetogenic chemotherapy: A randomized double-blind trial in 866
inductive effects of aprepitant on cytochrome P450 3A4 and 2C9
patients [abstract]. J Clin Oncol 2004;22 (Suppl 14):Abstract 8007.
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-6
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
activity. J Clin Pharmacol 2004;44:215-223. Available at:
91. Cassileth PA, Lusk EJ, Torri S, et al. Antiemetic efficacy of
dexamethasone therapy in patients receiving cancer chemotherapy. Arch Intern Med 1983;143:1347-1349. Available at:
84. Wampler G. The pharmacology and clinical effectiveness of
phenothiazines and related drugs for managing chemotherapy-induced emesis. Drugs 1983;25 Suppl 1:35-51. Available at:
92. Kris MG, Gralla RJ, Clark RA, et al. Consecutive dose-finding trials
adding lorazepam to the combination of metoclopramide plus dexamethasone: improved subjective effectiveness over the
85. Gralla RJ, Itri LM, Pisko SE, et al. Antiemetic efficacy of high-dose
combination of diphenhydramine plus metoclopramide plus
metoclopramide: randomized trials with placebo and prochlorperazine
dexamethasone. Cancer Treat Rep 1985;69:1257-1262. Available at:
in patients with chemotherapy-induced nausea and vomiting. N Engl J
Med 1981;305:905-909. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7024807.
93. Kris MG, Gralla RJ, Clark RA, et al. Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or
86. Gralla RJ, Tyson LB, Bordin LA, et al. Antiemetic therapy: a review
diphenhydramine when used in combination with metoclopramide plus
of recent studies and a report of a random assignment trial comparing
dexamethasone. A double-blind, randomized trial. Cancer
metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treat Rep
1987;60:2816-2822. Available at:
1984;68:163-172. Available at:
94. Herman TS, Einhorn LH, Jones SE, et al. Superiority of nabilone
87. Bakowski MT. Advances in anti-emetic therapy. Cancer Treat Rev
over prochlorperazine as an antiemetic in patients receiving cancer
1984;11:237-256. Available at:
chemotherapy. N Engl J Med 1979;300:1295-1297. Available at:
88. Grossman B, Lessin LS, Cohen P. Droperidol prevents nausea and
95. Steele N, Gralla RJ, Braun DW, Young CW. Double-blind
vomiting from cis-platinum. N Engl J Med 1979;301:47. Available at:
comparison of the antiemetic effects of nabilone and prochlorperazine
on chemotherapy-induced emesis. Cancer Treat Rep 1980;64:219-224. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6250699.
89. Aapro MS, Alberts DS. High-dose dexamethasone for prevention of cis-platin-induced vomiting. Cancer Chemother Pharmacol 1981;7:11-
96. Navari RM, Einhorn LH, Loehrer PJ, et al. A phase II trial of
14. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6122510.
olanzapine for the prevention of chemotherapy induced nausea and vomiting (CINV) [abstract]. J Clin Oncol 2004;22 (Suppl 14):Abstract
90. Aapro MS, Plezia PM, Alberts DS, et al. Double-blind crossover
8046. Available at:
study of the antiemetic efficacy of high-dose dexamethasone versus
high-dose metoclopramide. J Clin Oncol 1984;2:466-471. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6539363.
97. Navari RM, Einhorn LH, Passik SD, et al. A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier Oncology Group study. Support Care Cancer
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-7
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
2005;13:529-534. Available at:
105. Roila F, Warr D, Clark-Snow RA, et al. Delayed emesis:
moderately emetogenic chemotherapy. Support Care Cancer 2005;13:104-108. Available at:
98. Srivastava M, Brito-Dellan N, Davis MP, et al. Olanzapine as an
antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom Manage 2003;25:578-582. Available at:
106. Massa E, Astara G, Madeddu C, et al. Palonosetron plus
dexamethasone effectively prevents acute and delayed chemotherapy-induced nausea and vomiting following highly or moderately
99. Passik SD, Navari RM, Jung S-H, et al. A phase I trial of olanzapine
emetogenic chemotherapy in pre-treated patients who have failed to
(Zyprexa) for the prevention of delayed emesis in cancer patients: a
respond to a previous antiemetic treatment: comparison between
Hoosier Oncology Group study. Cancer Invest 2004;22:383-388.
elderly and non-elderly patient response. Crit Rev Oncol Hematol
Available at: http://www.ncbi.nlm.nih.gov/pubmed/15493359.
2009;70:83-91. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18723369.
100. Passik SD, Kirsh KL, Theobald DE, et al. A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in
107. Grunberg S, Clark-Snow RA, Koeller J. Chemotherapy-induced
cancer patients. J Pain Symptom Manage 2003;25:485-488. Available
nausea and vomiting: contemporary approaches to optimal
at: http://www.ncbi.nlm.nih.gov/pubmed/12727048.
management : Proceedings from a symposium at the 2008 Multinational Association of Supportive Care in Cancer (MASCC)
101. Passik SD, Lundberg J, Kirsh KL, et al. A pilot exploration of the
Annual Meeting. Support Care Cancer 2010. Available at:
antiemetic activity of olanzapine for the relief of nausea in patients with
advanced cancer and pain. J Pain Symptom Manage 2002;23:526-532. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12067777.
108. Ormrod D, Goa KL. Intranasal metoclopramide. Drugs 1999;58:315-322; discussion 323-314. Available at:
102. Morita T, Tei Y, Shishido H, Inoue S. Olanzapine-induced delirium
in a terminally ill cancer patient. J Pain Symptom Manage 2004;28:102-103. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15276190.
109. Maranzano E, Feyer P, Molassiotis A, et al. Evidence-based recommendations for the use of antiemetics in radiotherapy. Radiother
103. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone
Oncol 2005;76:227-233. Available at:
versus granisetron plus dexamethasone for prevention of nausea and
vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009;10:115-
110. Franzen L, Nyman J, Hagberg H, et al. A randomised placebo
124. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19135415.
controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 1996;7:587-592. Available at:
104. Geling O, Eichler H-G. Should 5-hydroxytryptamine-3 receptor
antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence
111. Wong RK, Paul N, Ding K, et al. 5-hydroxytryptamine-3 receptor
and drug cost implications. J Clin Oncol 2005;23:1289-1294. Available
antagonist with or without short-course dexamethasone in the
at: http://www.ncbi.nlm.nih.gov/pubmed/15718327.
prophylaxis of radiation induced emesis: a placebo-controlled
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-8
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
randomized trial of the National Cancer Institute of Canada Clinical
Altern Complement Med 2006;12:489-495. Available at:
Trials Group (SC19). J Clin Oncol 2006;24:3458-3464. Available at:
119. Figueroa-Moseley C, Jean-Pierre P, Roscoe JA, et al. Behavioral
112. Belkacemi Y, Ozsahin M, Pene F, et al. Total body irradiation prior
interventions in treating anticipatory nausea and vomiting. J Natl Compr
to bone marrow transplantation: efficacy and safety of granisetron in the
Canc Netw 2007;5:44-50. Available at:
prophylaxis and control of radiation-induced emesis. Int J Radiat Oncol
Biol Phys 1996;36:77-82. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8823261.
120. Molassiotis A, Yung HP, Yam BM, et al. The effectiveness of progressive muscle relaxation training in managing chemotherapy-
113. Okamoto S, Takahashi S, Tanosaki R, et al. Granisetron in the
induced nausea and vomiting in Chinese breast cancer patients: a
prevention of vomiting induced by conditioning for stem cell
randomised controlled trial. Support Care Cancer 2002;10:237-246.
transplantation: a prospective randomized study. Bone Marrow
Available at: http://www.ncbi.nlm.nih.gov/pubmed/11904789.
Transplant 1996;17:679-683. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8733681.
121. Razavi D, Delvaux N, Farvacques C, et al. Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant
114. Aapro MS, Molassiotis A, Olver I. Anticipatory nausea and
chemotherapy: a double-blind, placebo-controlled study assessing the
vomiting. Support Care Cancer 2005;13:117-121. Available at:
usefulness of alprazolam. J Clin Oncol 1993;11:1384-1390. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/8315437.
115. Ezzo J, Vickers A, Richardson MA, et al. Acupuncture-point
122. Malik IA, Khan WA, Qazilbash M, et al. Clinical efficacy of
stimulation for chemotherapy-induced nausea and vomiting. J Clin
lorazepam in prophylaxis of anticipatory, acute, and delayed nausea
Oncol 2005;23:7188-7198. Available at:
and vomiting induced by high doses of cisplatin. A prospective
randomized trial. Am J Clin Oncol 1995;18:170-175. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7900711.
116. Morrow GR, Morrell C. Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. N Engl J Med
123. Ellebaek E, Herrstedt J. Optimizing antiemetic therapy in multiple-
1982;307:1476-1480. Available at:
day and multiple cycles of chemotherapy. Curr Opin Support Palliat
Care 2008;2:28-34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18685391.
117. Redd WH, Andrykowski MA. Behavioral intervention in cancer treatment: controlling aversion reactions to chemotherapy. J Consult
124. Einhorn LH, Rapoport B, Koeller J, et al. Antiemetic therapy for
Clin Psychol 1982;50:1018-1029. Available at:
multiple-day chemotherapy and high-dose chemotherapy with stem cell
transplant: review and consensus statement. Support Care Cancer 2005;13:112-116. Available at:
118. Ezzo J, Streitberger K, Schneider A. Cochrane systematic reviews
examine P6 acupuncture-point stimulation for nausea and vomiting. J
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-9
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Antiemesis
125. Navari RM. Prevention of emesis from multiple-day and high-dose
germ cell cancer. Support Care Cancer 2007;15:1293-1300. Available
chemotherapy regimens. J Natl Compr Canc Netw 2007;5:51-59.
at: http://www.ncbi.nlm.nih.gov/pubmed/17436025.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17239326.
126. Herrstedt J, Sigsgaard TC, Nielsen HA, et al. Randomized,
double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy. Support Care Cancer 2007;15:417-426. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17093916.
127. Musso M, Scalone R, Bonanno V, et al. Palonosetron (Aloxi) and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving multiple-day chemotherapy. Support Care Cancer 2009;17:205-209. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18839220.
128. Celio L, Denaro A, Canova S, et al. Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting. Tumori 2008;94:447-452. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18822676.
129. Aapro MS, Grunberg SM, Manikhas GM, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 2006;17:1441-1449. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16766588.
130. Eisenberg P, MacKintosh FR, Ritch P, et al. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol 2004;15:330-337. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14760130.
131. Einhorn LH, Brames MJ, Dreicer R, et al. Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for
Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.REF-10
Source: http://enotes.us/CancerAntiEmesisRx2011.pdf
EHR Integration in Point of Service Systems: Patient Care Storyboard The Patient Medication Profile The Pharmaceutical Information Network (PIN) is one component of the EHR; it is the central repository of the patient's Medication Profile. Medication and allergy information is loaded into the EHR from pharmacies,
Symposium on Risk versus Hazard Symposium on Risk versus Hazard Risk versus Hazard – How to Regulate in the 21st Century Ragnar E. Lofstedt* In Europe, debate as to whether one should regulate chemicals based on intrinsic hazard or assessment of risk, or possibly a combination of both, has been gaining momentum. This article first provides a brief history of this risk versus hazard debate. Secondly, it ex-amines how European regulators are currently handling the regulation of two chemical compounds, namely Bisphenol A and Deca BDE (a brominated flame retardant), based on forty-five expert interviews with regulators, policy makers and industry representatives in eight Member States, as well as with European Commission officials. The paper shows that there is no clear consensus as to when risk or hazard considerations should be the basis for regulatory decision-making, with wide discrepancies between Member States (e.g. the UK is overall more risk based than Sweden) and between regulatory agencies within Member States. The penultimate section puts forward a series of recommendations to help regula-tors and policy makers develop more consistent and science based regulations for Europe.
