2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

acute and delayed nausea or vomiting after administration
of chemotherapy. Comparison of physician/nurse perception
to patient reality demonstrated that estimations of the
incidence of acute nausea and vomiting were quite accurate
but that the incidence of delayed nausea or vomiting was
markedly underestimated. In fact, the incidence of delayed
nausea or vomiting could be twice that estimated by experienced
health professionals. Underestimation of nausea
was more extreme than underestimation of vomiting, and
the problem was particularly apparent in patients receiving
moderately emetogenic chemotherapy (often patients with
breast cancer receiving a combination of cyclophosphamide
and an anthracycline). Studies using similar methodology
have now been repeated in various parts of the world,
including Mexico, 7 Venezuela, 8 and Taiwan. 9 Although absolute
values may change (in Taiwan 9 there was an overestimation
of the incidence of acute vomiting while in
Venezuela 8 delayed vomiting was a greater problem than
delayed nausea), the overall pattern of underestimation of
nausea and vomiting, particularly in the delayed setting
where patients are not being directly observed, remains. We
therefore urge oncology practices to adopt as a standard
operating procedure for administration of the first cycle of a
new chemotherapy either a single telephone call to the
patient or a single administration of a reporting tool such as
the Multinational Association of Supportive Care in Cancer
(MASCC) Antiemetic Tool (MAT) (which has been validated
for 3-day recall) several days after administration of chemotherapy
10 to more accurately describe problems that should
be addressed during future chemotherapeutic cycles.
Even if the existence of greater amounts of nausea and
vomiting than expected is accepted intellectually as a problem
for the overall population of patients receiving chemotherapy,
failure to accept the problem in terms of one’s own
patients may limit adoption of appropriate remedies. In a
very interesting study, Mertens and colleagues 11 evaluated
different strategies to encourage greater compliance with
generally accepted antiemetic guidelines in a single hospital.
Distribution of written educational materials concerning
the guidelines led to a transient increase in compliance to
these standards, but prescription habits soon returned to
KEY POINTS
● The current incidence of chemotherapy-induced nausea
and vomiting, particularly delayed nausea and
vomiting, is underestimated by physicians and
nurses.
● The incidence of clinically significant toxicities such
as nausea and vomiting for new agents should be
better defined during the drug development process.
● Real-time recording of patient-reported outcomes
through telephone contact or questionnaire is more
accurate than reports of toxicities recalled several
weeks after the event.
● Physicians should be aware that patient efforts to
appear strong and cooperative may lead to underreporting
of toxicities.
● Nausea and vomiting are separate phenomena that
may require unique remedies.
542
STEVEN M. GRUNBERG
baseline. A single Grand Rounds presentation concerning
antiemetics by a nationally recognized expert speaker had
no effect on antiemetic guideline compliance within the
hospital. The investigators then used diaries to survey
patients receiving chemotherapy concerning their emetic
experience and shared these results with the patients’ own
physicians. When the physicians were able to see persistent
nausea and vomiting not as abstract problems but as events
documented to be happening to their own patients, then a
durable increase in compliance with antiemetic guidelines
as reflected in antiemetic prescribing habits was achieved.
This is consistent with the observations by Stuebe 12 concerning
the value of Level I as compared to Level IV evidence
in clinical practice. Physicians learn intellectually from the
randomized double-blind clinical trials that are the basis of
Level I evidence. However, we remember and react to our
experiences with our own patients, and it is the Level IV
evidence of “adverse anecdotes” that is most likely to lead to
a durable improvement in practice. However, even if we are
willing to change practice based on the experience of our
patients, we must be able to understand what those experiences
are, and questions of communication therefore become
important. Salsman and colleagues 13 interviewed physicians
and patients concerning barriers to effective communication
regarding treatment of chemotherapy-induced
nausea and vomiting and found interesting similarities as
well as interesting differences. Both physicians and patients
indicated a desire to minimize the number of medications
that were being taken to avoid drug-drug interactions
and side effects. This can be a positive goal as long as it
does not lead to underutilization of effective and necessary
remedies. A significant percentage of physicians and patients
suggested that the presence of nausea and vomiting
is an indication that chemotherapy is working. This is
disturbing since no relationship between the intensity of
chemotherapy-induced nausea and vomiting and the effectiveness
of chemotherapy has ever been demonstrated. Failure
to use available effective antiemetics due to a mistaken
belief that such a course of action was preserving therapeutic
efficacy would be a disservice to everyone involved. Of
particular concern was the finding that patients wanted to
“be strong” and not complain to their physicians, while
physicians believed that patients would report serious adverse
events if they occurred. This disconnect in communication
in and of itself could lead to undertreatment of
chemotherapy-induced nausea and vomiting even if potentially
effective agents were available.
An additional concept that may lead to the development of
more effective antiemetic agents is the realization that
nausea and vomiting are not manifestations of the same
phenomenon but rather two separate phenomena. 14 It has
long been assumed that nausea is simply the prodrome of
vomiting and that agents that relieve vomiting will therefore
certainly relieve nausea as well. This belief is the
justification for the use of antiemetic clinical trial endpoints
such as complete response (no vomiting and no use of rescue
medication), which do not even mention the term “nausea”
as sufficient for regulatory approval of agents not just to
prevent vomiting but rather to prevent “nausea and vomiting.”
In reality, vomiting is an objective endpoint (expulsion
of stomach contents), while nausea is a subjective endpoint
that is more difficult to localize or define. Because nausea is