original articles Annals of Oncology

Annals of Oncology 23: 1986–1992, 2012

doi:10.1093/annonc/mds021
Published online 6 March 2012

The effect of guideline-consistent antiemetic therapy

on chemotherapy-induced nausea and vomiting
(CINV): the Pan European Emesis Registry (PEER)
M. Aapro1*, A. Molassiotis2, M. Dicato3, I. Peláez4, Á. Rodríguez-Lescure5, D. Pastorelli6, L. Ma7*,
T. Burke7, A. Gu7, P. Gascon8 & F. Roila9 on behalf of the PEER investigators
1
Medical Oncology and Radiation, IMO Clinique de Genolier, Genolier, Switzerland; 2School of Nursing Midwifery and Social Work, University of Manchester,
Manchester, UK; 3Hematology-Oncology, Luxembourg Medical Center, Luxembourg, Luxembourg; 4Hospital de Cabuenes, Gijón, Spain; 5Medical Oncology, Hospital
General Universitario de Elche, Elche, Spain; 6Oncologic Institute of the Veneto, Padova, Italy; 7Global Health Outcomes, Merck Sharp & Dohme Corp., Whitehouse
Station, USA; 8Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona, Barcelona, Spain; 9Medical Oncology, Santa Maria Hospital, Terni, Italy

Received 2 November 2011; revised 6 January 2012; accepted 13 January 2012

Background: While guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) are widely available,
clinical uptake of guidelines remains low. Our objective was to evaluate the effect of guideline-consistent CINV
prophylaxis (GCCP) on patient outcomes.
Patients and methods: This prospective, observational multicenter study enrolled chemotherapy-naive adults
initiating single-day highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer. Patients completed 6-
day daily diaries beginning with cycle 1 for up to three chemotherapy cycles. The primary study end point, complete
response (no emesis and no use of rescue therapy) during 120 h after cycle 1 chemotherapy, was compared between
GCCP and guideline-inconsistent CINV prophylaxis (GICP) cohorts using multivariate logistic regression, adjusting for
potential confounding factors.
Results: In cycle 1 (N = 991), use of GCCP was 55 % and 46 % during acute and delayed phases, respectively, and
29 % for the overall study period (acute plus delayed phases). Complete response was recorded by 172/287 (59.9 % )
and 357/704 (50.7 % ) patients in GCCP and GICP cohorts, respectively (P = 0.008). The adjusted odds ratio for
complete response was 1.43 (95 % confidence interval 1.04–1.97; P = 0.027) for patients receiving GCCP versus GICP.
Conclusion: GCCP reduces the incidence of CINV after single-day HEC and MEC.
Key words: antiemetic therapy, chemotherapy, emesis, guidelines, nausea

introduction 30 % –90 % receiving moderately emetogenic chemotherapy

Several evidence-based consensus guidelines for preventing
chemotherapy-induced nausea and vomiting (CINV) are
published and regularly updated [1–3]. However, studies
suggest that the clinical uptake of antiemetic guidelines is often
suboptimal, and CINV is a persistent problem for patients
receiving chemotherapy [4–8]. Patients who experience CINV
may be discouraged from completing their chemotherapy
regimen; CINV adversely impacts both quality of life and the
ability to carry out the activities of daily living [9–11].
Moreover, patients with emesis may require emergency care or
hospitalization, adding to the economic burden of cancer care
[12, 13].
In the absence of antiemetic therapy, > 90 % of patients
receiving highly emetogenic chemotherapy (HEC) and
*Correspondence to: Dr M. Aapro, Clinique de Genolier, Institut Multidisciplinaire
d’Oncologie IMO, Case Postale (PO Box) 100, Route du Muids 3, Genolier 1272,
Switzerland. Tel: +41-223669106; Fax: +41-223669207; E-mail: maapro@genolier.net
(MEC) experience CINV. The occurrence of CINV is typically
biphasic; thus, recommendations for antiemetic therapy are
targeted to prevent CINV in the acute phase, occurring in the
first 24 h, and the delayed phase, occurring > 24 h after
chemotherapy [14–16]. Prevention of CINV from the start of
chemotherapy is important, both because delayed emesis is
correlated with the presence of acute emesis [17] and because
patients who experience CINV in one cycle are more likely to
develop anticipatory CINV during subsequent chemotherapy
cycles [14].
There are a number of observational studies evaluating the
effectiveness of different antiemetic regimens and the optimal
means of implementing antiemetic guidelines in practice, but
the effect of guideline adherence in preventing CINV has not
been systematically studied [18–20]. The primary objective of
this prospective observational study was to analyze the
proportions of patients with complete response (no emesis and
no use of rescue therapy) during the first 120 h after cycle 1

© The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com
Annals of Oncology
HEC or MEC among patients receiving guideline-consistent
CINV prophylaxis (GCCP) as compared with guideline-
inconsistent CINV prophylaxis (GICP). Our hypothesis was
that use of GCCP, as compared with GICP, would result in a
greater proportion of patients achieving complete response in
the 120 h after the initiation of HEC or MEC. Secondary study
objectives were to describe the use of CINV prophylaxis for
HEC and MEC in European clinical practice and to describe
the experience of nausea and vomiting among patients
receiving GCCP or GICP for HEC and MEC.
patients and methods
study design
This prospective observational study was conducted from September 2009
to June 2010 in eight European countries, including Austria, Belgium,
France, Italy, Spain, Sweden, The Netherlands, and UK.
patients
Male and female outpatients (aged ≥ 18 years) who were chemotherapy
naive and scheduled to receive at least two cycles of single-day HEC or
MEC were eligible for inclusion in the study. Intended treatment of cancer
was with a minimum of any one of the following agents: cisplatin,
cyclophosphamide, dacarbazine, oxaliplatin, carboplatin, doxorubicin,
epirubicin, irinotecan, oral temozolomide, oral vinorelbine. Patients were
excluded from the study if they received chronic systemic corticosteroid
therapy, concurrent abdominal or pelvic radiation therapy, or HEC or
MEC within 120 h (5 days) after day 1 chemotherapy administration.
Other key exclusion criteria were the presence of brain metastases or
vomiting in the 24 h before chemotherapy.
procedures
The study was approved by the local ethics committee at each site, and
patients gave written informed consent. Adult patients initiating HEC or
MEC were recruited consecutively at study sites (hospital, community, and
private oncology clinics). Patients completed 6-day daily diaries beginning
on the day of single-day chemotherapy and for one to three chemotherapy
cycles. The study was designed specifically to avoid influencing treatment
decisions or inducing any study-specific investigations.
Electronic data capture forms were used to record demographic and
clinical data from source documents, including patient diaries, and to
complete investigator site questionnaires. Study sites anonymized any
patient identifiers before forwarding information to be recorded on the
Table 1. Definition of guideline-consistent chemotherapy-induced nausea and vomiting prophylaxis (GCCP), based on MASCC 2006 guidelines [22]
Chemotherapy Acute phase (day 1) GCCP
HEC Corticosteroid + NK1-RA + 5HT3-RA
Female AC Corticosteroid + NK1-RA + 5HT3-RAa
MEC Corticosteroid + 5HT3-RAa,b
a
All 5HT3-RA were considered equivalent and interchangeable. Oral and i.v. formulations of corticosteroid, 5HT3-RA, and NK1-RA were considered
equivalent and interchangeable.
b
Palonosetron on day 1 was considered to provide prophylaxis on days 2–3 for MEC.
c
The study GCCP definition differs from MASCC 2006 guidelines in the delayed phase for female AC and MEC by permitting use of both listed agents
(+/or instead of or).
AC, anthracycline plus cyclophosphamide; HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy; NK1-RA, neurokinin-1
receptor antagonist; 5HT3-RA, 5-hydroxytryptamine-3 receptor antagonist.
Volume 23 | No. 8 | August 2012
original articles
electronic data capture form via double data entry. Data collected with
regard to cancer chemotherapy included the intended and actual
chemotherapy regimens, antiemetic therapy, and any rescue medications
used, administered, or prescribed (drug, dosage, and formulation for all).
Patients completed the daily diary beginning before chemotherapy (on
day 1) and for a total of six calendar days. Before chemotherapy
administration, patients recorded whether they had any emesis in the prior
24 h and, on three separate visual analogue scales (VAS, scored from 0,
none, to 100, maximum), whether they had any nausea or anxiety in the
prior 24 h or any expectation of nausea. On subsequent days, items in the
diary, with the exception of emetic events, were recorded with reference to
the prior 24 h, and study results were thus defined in 24-h increments
beginning at the time of initiation of chemotherapy: day 1 (acute phase)
was the 24-h period after the initiation of chemotherapy, and days 2–5
(delayed phase) were the 24- to 120-h period after initiation of
chemotherapy. Patients recorded the time and date of emetic episodes, the
severity of nausea and of anxiety (0–100 VAS), and use of rescue
medication (type and dosage). On day 6 of cycle 1, patients recorded use of
complementary therapies (such as acupressure, herbal remedies, yoga, and
relaxation techniques) and health care visits to manage nausea or vomiting
in the prior 5 days. Completion of the cycle 1 diary was required for
patients to continue in the study to cycle 2, and completion of the cycle 2
diary, to continue to cycle 3.
Chemotherapy regimens were categorized according to international
guidelines based on the emetogenic potential of the agent in the regimen
with the highest emetic risk [21]. Our study definition of guideline
consistency of antiemetic therapy (GCCP) closely followed the 2006
antiemetic guidelines of the Multinational Association of Supportive Care
in Cancer (MASCC) [22] and was based, without imposing minimal doses,
on whether recommended drugs were administered or prescribed on the
recommended days (Table 1). Patients administered or prescribed the
recommended drugs on each day of the overall (acute and delayed phases)
period were classified as receiving GCCP for the overall phase. All other
patients were classified as receiving GICP during the overall phase.
outcome assessments
The primary study end point of complete response was defined as no
emesis and no use of rescue therapy to relieve symptoms of nausea or
vomiting. No emesis was defined as no vomiting (expulsion of stomach
contents through mouth) and no retching (nonproductive attempts to
vomit). Distinct emesis episodes were separated by the absence of vomiting
and retching for at least 1 min. No nausea was defined as nausea scored as
< 5 on the VAS. No CINV was defined as no emesis and no nausea. Rescue
medication was defined as any medication taken in addition to
prophylactic treatment for control of nausea or vomiting. Secondary
Delayed phase (days 2–4) GCCP
a
Corticosteroid days 2–4 + NK1-RA days 2–3
Corticosteroid +/or NK1-RA days 2–3c
Corticosteroid +/or 5HT3-RA days 2–3c
doi:10.1093/annonc/mds021 | 
original articles Annals of Oncology

antiemetic agents included any antiemetic other than the three primary Table 2. Patient demographic and clinical characteristics
classes of antiemetic agents (corticosteroids, neurokinin-1 receptor
antagonists [NK1-RAs], and 5-hydroxytryptamine-3 receptor antagonists Characteristic GCCP GICP Overall Pa
[5-HT3-RAs]). (N = 287) (N = 704) (N = 991)
Mean age, years (SD) 57.1 (11.7) 56.6 (11.2) 56.7 (11.4) 0.542
statistical analyses Female 225 (78.4) 497 (70.6) 722 (72.9) 0.012
Patient characteristics and study end points were summarized using Primary cancer diagnosis
descriptive statistics. Categorical and continuous variables were compared Breast 157 (54.7) 368 (52.3) 525 (53.0) < 0.001
between GCCP and GICP cohorts using Pearson’s χ2 test and Student’s t Colorectal 47 (16.4) 79 (11.2) 126 (12.7)
test, respectively. Multivariate logistic regressions were used to compare Lung 21 (7.3) 90 (12.8) 111 (11.2)
proportions of patients (GCCP versus GICP) achieving complete response Ovarian 20 (7.0) 31 (4.4) 51 (5.1)
during the study period of 120 h after initiation of cycle 1 chemotherapy Other 42 (14.6) 136 (19.3) 178 (18.0)
( primary end point), as well as other CINV outcomes, including no emesis, Metastatic disease 65 (22.6) 228 (32.4) 293 (29.6) 0.002
no nausea, and no CINV. The models included GCCP/GICP as a binary History of nausea or 79 (28.0) 141 (20.4) 220 (22.6) 0.010
variable and other relevant demographic and clinical variables. Multivariate vomiting
Poisson regression was used to compare the count of health care visits due Alcohol use (≥10 drinks per 22 (7.8) 83 (12.0) 105 (10.8) 0.056
to CINV in cycle 1 between the GCCP and GICP cohorts. Statistical week)
significance was assessed at the two-sided 0.05 level. Chemotherapy emetic risk category
The study was planned to have 80 % power to detect a 10-percentage HEC 21 (7.3) 168 (23.9) 189 (19.1) < 0.001
point between-group difference (α = 0.05, two-sided) in complete response Female AC 133 (46.3) 330 (46.9) 463 (46.7)
with 300 assessable patients in the GCCP cohort and 900 patients in the MEC 133 (46.3) 206 (29.3) 339 (34.2)
GICP cohort, assuming a 55 % complete response in the guideline- Pre-chemotherapy diary question responses (0–100 VAS), mean (SD)
consistent group and a 45 % complete response in the guideline- Pre-chemotherapy 27 (30) 32 (32) 30 (32) 0.037
inconsistent group. anxietyb
Expectation of nauseab 30 (31) 36 (32) 34 (32) 0.020

results Values represent number ( % ) of patients unless otherwise noted.

a
Chi-square test for categorical values; t test for continuous variables for
patients the comparisons between GCCP and GICP cohorts.
A total of 1128 eligible patients were enrolled from 52 study b
Measured during the 24-h period before start of chemotherapy.
sites; of these, 991 (87.9 % ), 888 (78.7 % ), and 769 (68.2 % ) AC, anthracycline plus cyclophosphamide; CINV, chemotherapy-induced
patients received single-day chemotherapy and completed nausea and vomiting; GCCP, guideline-consistent CINV prophylaxis;
diaries for chemotherapy cycles 1, 2, and 3, respectively. The GICP, guideline-inconsistent CINV prophylaxis; HEC, highly emetogenic
remaining 137 patients were excluded from study because they chemotherapy; MEC, moderately emetogenic chemotherapy; VAS, visual
did not complete the cycle 1 diary (n = 102), they did not analogue scale
receive intended chemotherapy (n = 26), or they received HEC
or MEC within 120 h after day 1 chemotherapy (n = 9).
Table 2 summarizes demographic and clinical characteristics
for patients included in the analyses for cycle 1. Patients
ranged in age from 19 to 84 years, with mean age of 57 years
in both cohorts. Almost three quarters of patients were women,
with a significantly greater proportion of women in the GCCP
cohort, and 99 % of patients were white. Breast cancer was the
most common diagnosis. Overall, one-fifth of patients received
HEC, almost half were women who received anthracycline plus
cyclophosphamide (female AC), and the remaining patients
(34 % ) received MEC (see Table 2).

antiemetic therapy
Antiemetic therapies prescribed for cycle 1 of single-day
chemotherapy are summarized in online Supplemental Table
S1 (available at Annals of Oncology online) for the acute and
delayed phases according to guideline consistency. The use of
GCCP varied substantially between acute and delayed phases
and among the three categories of chemotherapy emetogenicity
(Figure 1). Of the emetic risk categories, HEC represented a
higher proportion of GICP than GCCP (23.9 % versus 7.3 % ),
while MEC was a higher proportion of GCCP than GICP
(46.3 % versus 29.3 % ; see Table 2). Guideline consistency was
highest overall (acute and delayed phases) for patients receiving
Figure 1. Prevalence of guideline-consistent CINV prophylaxis (GCCP)
for cycle 1 single-day chemotherapy, by emetogenicity of chemotherapy
and for the total study population. For the overall study period, patient
assignment to the GCCP cohort was based on guideline consistency during
both acute and delayed phases (0–120 h post-chemotherapy). AC,
anthracycline plus cyclophosphamide; HEC, highly emetogenic
chemotherapy; MEC, moderately emetogenic chemotherapy.
MEC and higher in the acute than the delayed phase for
patients who received HEC or MEC. For female AC, guideline
consistency was higher in the delayed than the acute phase, in

 | Aapro et al. Volume 23 | No. 8 | August 2012

Annals of Oncology
part, because we included as GCCP the prescription of
corticosteroid and/or (rather than ‘or’) NK1-RA.
The reasons for guideline inconsistency within the GICP
group varied across emetogenic risk group (see online
supplementalTable S2, available at Annals of Oncology online).
For HEC GICP patients, non-prescribing of corticosteroid
(delayed phase, range from 16.1 % to 38.7 % ) and NK1-RA
(acute phase, 51.8 % ) were the most common reasons for
guideline inconsistency. For female AC and MEC, the primary
reasons for guideline inconsistent prescribing were non-
prescribing of NK1-RA use (acute phase, 7 % ) and
corticosteroid and/or 5HT3-RA (delayed phase, 6.3 % to 29.6
% ), respectively.
Secondary antiemetic therapies were prescribed to 29 % of
patients overall with no significant difference between GCCP
and GICP cohorts (31.0 % versus 28.1 % , P = 0.364; online
Supplemental Table S3, available at Annals of Oncology online).
Of the secondary antiemetic therapies, benzodiazepines were
prescribed significantly more frequently in the GCCP cohort
(10.5 % versus 1.0 % , P < 0.001) and benzamides, in the GICP
cohort (13.2 % versus 24.4 % , P < 0.001). The overall use of
complementary therapies, most commonly herbal supplements
or special foods (e.g. ginger, fennel seeds) to prevent or
manage vomiting or nausea, was similar in the two cohorts
(16.7 % versus 18.3 % , P = 0.55).
CINV events
The percentage of patients with complete response (no emesis
or rescue therapy) was significantly higher in the GCCP cohort
than in the GICP cohort during both acute and delayed phases
as well as overall (during 120 h post-chemotherapy; Table 3).
Moreover, the proportions of patients with other desirable
CINV outcomes (no emesis, no nausea, and no CINV) were
higher in the GCCP than the GICP cohort in all phases, with
the differences either being statistically significant or suggesting
a strong trend. For all CINV end point results, the differences
between GCCP and GICP cohorts were numerically greater in
the acute than the delayed phase (see Table 3).
Table 3. Chemotherapy-induced nausea and vomiting (CINV) outcomes
by guideline consistency (GCCP versus GICP) in cycle 1 overall phase:
unadjusted and adjusted results
a b
GCCP GICP P Multivariate model
(N = 287) (N = 704) Odds ratio P GP visit
Complete response 172 (59.9) 357 (50.7) 0.008 1.43 (1.04–1.97)
No emesis 182 (63.4) 412 (58.5) 0.154 1.18 (0.86–1.63)
No nausea 138 (48.1) 286 (40.6) 0.031 1.37 (0.99–1.90)
No CINV 122 (42.5) 242 (34.4) 0.016 1.41 (1.01–1.96)
a
Chi-square test.
b b
Model adjusted for age, sex, pre-chemotherapy nausea, pre-chemotherapy
anxiety, expectation of nausea, use of primary antiemetic therapy not
recommended by guidelines, underdosing of primary antiemetic therapy,
and use of secondary antiemetic agents.
GCCP, guideline-consistent CINV prophylaxis; GICP, guideline-
inconsistent CINV prophylaxis.
Volume 23 | No. 8 | August 2012
original articles
Patients classified as GCCP had 1.43 times the odds of
complete response (95 % confidence interval 1.04–1.97; P =
0.027) in the overall study period compared with patients
receiving GICP, controlling for confounding factors (see
Table 3). Similar statistically significant results were observed
for the acute and delayed phases, though differences in CINV
between the GCCP and GICP groups were larger for the acute
than delayed phase (online supplemental Table S4, available at
Annals of Oncology online). The results for CINV end points
during cycles 2 and 3 supported cycle 1 results (online
supplemental Table S5, available at Annals of Oncology online).
The proportions of patients using health care resources
during the 5 days after chemotherapy tended to be lower in the
GCCP than the GICP cohort (Table 4). Visits to a general
practitioner were the most frequent. Compared with those in
the GICP cohort, patients in the GCCP cohort had
significantly fewer visits to specialists and the emergency room
during the 5-day post-chemotherapy period.
discussion
Among chemotherapy-naive patients who received HEC or
MEC in this large prospective study, the proportion with
complete response (no emesis or rescue therapy) during the
first 120 h after cycle 1 was significantly higher among those
receiving GCCP than those receiving GICP. Overall, almost 10
% more patients receiving GCCP achieved complete response
as compared with GICP. An improvement of 10 % in complete
response is considered to be a clinically meaningful difference
[21]. The beneficial effect of GCCP in promoting complete
response persisted after controlling for confounding factors.
There was a consistent benefit of GCCP across CINV end
points, and the results for cycles 2 and 3 were consistent with
those for cycle 1. Guideline consistency in the acute phase of
cycle 1 was highly significant in reducing CINV, including
nausea, in the acute phase: in multivariate analyses, adjusted
odds ratios for absence of CINV were significantly higher for
the GCCP cohort. The benefits of GCCP tended to be less
pronounced in the delayed phase, although the odds ratio for
Table 4. Health care visits to manage CINV over 5 days after initiation of
chemotherapy—cycle 1
Parameter GCCP GICP Multivariate modelb
(N = 287) (N = 704) Rate ratio (95 % CI) P
7 (2.4)a 29 (4.1) 0.68 (0.45–1.02) 0.062
0.027 Specialist visit 3 (1.1) 11 (1.6) 0.51 (0.34–0.79) 0.002
0.301 ER visit 4 (1.4) 12 (1.7) 0.57 (0.38–0.84) 0.004
0.056 Hospital days 5 (1.7) 10 (1.4) 1.22 (0.79–1.86) 0.364
0.041 a
Values represent total number of visits (normalized to number of visits
per 100 patients).
P values derived from Poisson regression models, accounting for
overdispersion, adjusting for the same set of confounding factors as those
applied in the multivariate analyses depicted in Table 3.
CINV, chemotherapy-induced nausea and vomiting; ER, emergency room;
GCCP, guideline-consistent CINV prophylaxis; GICP, guideline-
inconsistent CINV prophylaxis; GP, general practitioner.
doi:10.1093/annonc/mds021 | 
original articles
the primary end point, complete response, was significantly
greater in the GCCP cohort. These findings parallel published
observations that, in routine practice, nausea and delayed
symptoms remain the most challenging to manage [11, 23–26].
The use of GCCP was relatively low overall (29 % ) and
lowest (11 % ) for patients in the highest emetic risk category,
most commonly because of the less than optimal use of NK1-
RA and corticosteroids, particularly out to day 4.
Patients receiving GCCP had significantly fewer specialist
and emergency room visits to manage CINV over the 5 days
after chemotherapy than those receiving GICP and marginally
nonsignificantly fewer general practice visits (P = 0.06). While
the absolute numbers of hospital days and clinic and
emergency visits due to CINV were not large, the differences
between cohorts could have important economic and clinical
implications considering the many patients treated with
multiple cycles of HEC and MEC regimens on an annual basis
throughout Europe.
This large prospective study has enabled us to examine
antiemetic prescribing patterns across a range of European
countries and oncology centers. The sample size, consisting of
nearly 1000 assessable patients treated with MEC or HEC,
provides a robust evaluation of the benefits of guideline-
consistent prophylaxis of CINV, including the newest
antiemetic therapies, aprepitant and palonosetron. As a result,
the study results will generalize well to current Western
European clinical practice.
A weakness of the study is that the GCCP classification was
based on CINV prophylaxis as prescribed for oral agents,
rather than on actual use by patients. Therefore, patients who
failed to adhere to the prescribed regimen would have been
misclassified, likely leading to an underestimation of the
differences between GCCP and GICP. Moreover, we cannot
rule out the possibility of omissions or errors by patients in the
diaries. Other study weaknesses include those common to
observational studies, namely, cohort assignment based on
physician prescribing rather than randomization, resulting in
baseline differences between study cohorts and potential
confounding by indication. The use of multivariate logistic
regression addresses the latter limitation; however, statistically
significant differences could occur due to chance.
Comparisons with previous studies on the prevalence and
effect of guideline consistency are complicated by differing
guidelines, definitions of consistency, time periods, locations,
and patient populations. Adherence to guidelines in earlier
single-center studies in the United States and Europe was
reportedly better for the acute than the delayed phase [4, 5, 8],
consistent with our findings for the total study population.
Similarly, earlier studies that evaluated the effect of guideline
implementation reported better antiemetic outcomes as
guideline adherence increased; these were smaller single-center
studies based in the United States before the availability of
aprepitant and palonosetron [5, 19, 20].
The emetogenicity of chemotherapy is accepted as the most
important risk factor for CINV and is used to guide selection
of antiemetic therapy [14]. Our findings provide support for
the use of GCCP to reduce the incidence of CINV after cycle 1
HEC, female AC, and MEC. The low prevalence of GCCP in
the highest emetogenic risk regimens (11 % for HEC) may
 | Aapro et al.
Annals of Oncology
reflect economic constraints of hospitals and government
payers considering the higher costs of branded-only antiemetic
therapies. Nonetheless, this is an area especially needing
improvement, and providing appropriate CINV prophylaxis to
the subgroups of patients at highest risk of CINV will likely
have the greatest impact on improving patient outcomes.
Comprehensive and long-term efforts consisting of efficient
education, training, and monitoring of all individuals involved
are needed to achieve better adherence to antiemetic guidelines
[6, 7]. Key components of successful prior multifaceted
strategies to improve guideline adherence include educational
outreach visits by opinion leaders [18, 20], the use of
standardized antiemetic protocols included in chemotherapy
order forms [19], providing feedback to clinicians on the
extent and severity of patient CINV outcomes [5], and clinical
interventions by pharmacists in the event of inappropriate
antiemetic orders [20].
Our study results indicate that there is a significant benefit of
guideline-consistent antiemetic therapy across a range of CINV
end points in the acute and delayed phases and overall. The
incidence of CINV was relatively high, and the prevalence of
GCCP relatively low, for the overall study period. Trends favored
the GCCP group for lower health care resource use secondary to
CINV. The results of this observational study highlight the need
to improve the transferability to clinical practice of antiemetic
research. Studies are needed to explore the barriers to guideline
use for clinicians and to test the effects of different strategies to
enhance their use of guidelines. Strategies targeting patients
receiving HEC or females receiving AC regimens, where
adherence is lower and outcomes poorer are recommended.
Education on guideline recommendations for corticosteroids
(primarily delayed phase) and NK1-RA (overall phase) within
these subgroups is also recommended. Better communication
and implementation of antiemetic guidelines must be
considered as a means to reduce the burden of CINV.
acknowledgements
We thank all the investigators who participated in this study
( please see Appendix for listing of Chief Investigators by
study site).
funding
This work was supported by Merck Sharp & Dohme Corp.
Medical writing and editorial assistance was provided by
Elizabeth V. Hillyer and funded by Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc., Whitehouse
Station, NJ.
disclosure
MA holds no shares in any drug company or in mutual funds
investing exclusively in pharma; he has received study grants,
honoraria for consultancy, and/or is on the speaker bureau of
Abraxis, Amgen, AstraZeneca, Bayer Schering, Bristol-Myers,
Celgene, Cephalon, GSK, Helsinn, Hospira, Johnson and
Johnson Ortho Biotech, Merck, MSD, Novartis, Pfizer,
Pierre-Fabre, Roche, Sandoz, Schering, sanofi-aventis, Vifor.
Volume 23 | No. 8 | August 2012
Annals of Oncology
AM has served in the advisory board and received honoraria
and research funding from Merck & Co Ltd; received
honoraria and research funding from Roche UK Ltd; research
funding from Acacia Pharma; and honoraria from ProStrakan
and Bayer. MMD is a member of the Merck speakers bureau
and advisory board. IP, ÁR-L, DP, and AG have no conflicts to
declare. PG is a member of a Merck advisory board. LM was
an employee of Merck at the time of the study. TB is an
employee of Merck. FR has served on the advisory board and
received honoraria from Merck. All remaining authors have
declared no conflicts of interest.
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appendix
Chief Investigators for the Pan European Emesis Registry
(PEER) are listed below.
Austria: Paul Sevelda (Vienna General Hospital), Herbert
Watzke (Medical University Vienna), Guntram Winder
(Hospital Dornbirn), Richard Greil (University Hospital
Salzburg), Alois Lang (Hospital Rankweil); Belgium: Simon
Van Belle (UZ Gent), Dirk Schrijvers (ZNA Middelheim),
Didier Verhoeven (AZ KLINA), Wim Demey (AZ Sint-Jozef ),
Francoise Majois (Centre Hospitalier Jolimont La Louvière),
Frederique Bustin (CHR de la Citadelle Liège), Chantal Andre
(CHR de la Citadelle Liège); France: Marc Espie (Hôpital Saint
-Louis), Maya Hacini (Hôpital Chambery), Anne-Claire Hardy
Bessard (Clinique Armoricaine), Nicolas Isambert (Centre G-F
Leclerc), Alain Lortholary (Centre Catherine de Sienne),
Pierre-Jean Souquet (CH Lyon Sud), Mohamed Hebbar
(CHRU Lille-hôpital Claude Huriez); Italy: Massimiliano
Berretta (Centro di Riferimento Oncologico IRCCS), Claudio
Dazzi (Presidio Ospedaliero S. Maria delle Croci), Manlio
Ferrarini (Istituto Nazionale per la Ricerca sul Cancro IRCCS),
Marzia Locatelli (Istituto Europeo di Oncologia IRCCS), Vito
Lorusso (Presidio Ospedaliero Vito Fazzi, Polo Oncologico
Giovanni Paolo II), Paolo Marchetti (Azienda Ospedaliera
S. Andrea), Andrea Martoni (Azienda Ospedaliero-
Universitaria Policlinico S.Orsola-Malpighi), Davide Pastorelli
(Istituto Oncologico Veneto IRCCS), Sandro Pignata
(Fondazione Giovanni Pascale, Istituto Nazionale per lo Studio
e la Cura dei Tumori IRCCS), Monica Giordano (Az.
Ospedaliera Sant’Anna); Netherlands: Joachim Aerts (Amphia
Zkhs, Loc Molengracht), Reinoud Blaisse (Alysis Zorggroep,
Loc Rijnstate), Agnis van der Wouw (VieCuri MC Noord-
Limburg); Spain: Ignacio Peláez (Hospital de Cabueñes), Silvia
doi:10.1093/annonc/mds021 | 
original articles Annals of Oncology

Antolin Novoa (Hospital Teresa Herrera—Complejo
Hospitalario Universitario A Coruña-CHUAC), Jose Esteban
Salgado Pascual (Hospital de Navarra), Vicente Alberola
Candel (Hospital Arnau de Vilanova), Álvaro Rodríguez-
Lescure (Hospital General Universitario de Elche), Laura
Palomar (Hospital Universitario La Fe), Virtudes Soriano
Teruel (Instituto Valenciano de Oncologia); UK: Mike Bayne
(Dorset County Hospital), Karen McAdam (Peterborough and
Stamford Hospitals), Alex Molassiotis (The University of
Manchester & Christie Hospital NHS Foundation Trust),
Elaine Rankin (Ninewells Hospital and Medical School), Leslie
Samuel (Aberdeen Royal Infirmary), Anirban Chatterjee (Royal
Shrewsbury Hospital), Sarah Khan (Nottingham University
Hospital and King’s Mill Hospital), Neville Davidson
(Broomfield Hospital); Sweden: Max Flogegard
(Blodmottagningen); Bengt Norberg (Onkolog Kliniken), Petra
Flygare (Onkolog Kliniken #9097), Bo Nordenskjold
(Onkologkliniken).

Annals of Oncology 23: 1992–1998, 2012

doi:10.1093/annonc/mds141
Published online 13 June 2012

Daily skin care habits and the risk of skin eruptions

and symptoms in cancer patients
H. J. Byun1,2,3, H. J. Lee4,5*, J. I. Yang6, K. H. Kim1,2,3, K. O. Park7, S. M. Park7,8, K. E. Lee5,9,
J. Choi10, D.-Y. Noh5,11 & K. H. Cho1,2,3*
1
Skin Cancer/Chemotherapy Skin Care Center, Seoul National University Cancer Hospital, Seoul;; 2Department of Dermatology, Seoul, National University College of
Medicine, Seoul;; 3Institute of Dermatological Science, Medical Research Center, Seoul National University, Seoul;; 4Gastric Cancer Center, Seoul National University
Cancer Hospital, Seoul;; 5Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul;; 6Department of Internal Medicine,
Healthcare Research Institute, Seoul National University Hospital Gangnam Healthcare Center, Seoul;; 7Center for Cancer Education and Information, Seoul National
University Cancer Hospital and Department of Nursing, Seoul National University Hospital, Seoul;; 8Department of Family Medicine, Seoul National University College of
Medicine, Seoul;; 9Thyroid Cancer Center, Seoul National University Cancer Hospital, Seoul;; 10Department of Biomedical Engineering, Seoul National University College
of Medicine, Seoul;; 11Breast Cancer Center Seoul National University Cancer Hospital, Seoul, South Korea

Received 15 November 2011; revised 29 March 2012; accepted 10 April 2012

Background: Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible
to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer
patients have rarely been studied.
Patients and methods: We conducted a survey of daily skin care habits and the presence of skin problems in 866
cancer patients.
Results: Hot water bath >1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of
itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and
symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of
definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total
results, including that hot water bath >1 h significantly increased the risk of definite eruptions (OR 3.41).
Conclusions: Being a cross-sectional study, our study could not prove causality. However, at the present stage of
knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to
prevent skin problems in cancer patients.
Key words: bath, cancer, eruptions, itching, moisturizer, skin care habits

introduction cytotoxic agents and radiation therapy. To overcome the

Cancer patients are at high risk for skin problems because
rapidly proliferating skin cells are susceptible to anticancer
*Correspondence to: Prof. H. J. Lee, Department of Surgery and Cancer Research
Institute, Seoul National University College of Medicine, 101 Daehang-ro, Jongno-gu,
Seoul 110-744, South Korea. Tel: +82-2-766-3975; Fax: +82-2-766-3975;
E-mail: appe98@snu.ac.kr; Prof. K. H. Cho, Department of Dermatology, Seoul National
University College of Medicine, 101 Daehang-ro, Jongno-gu, Seoul 110-744, South
Korea. Tel: +82-2-2072-2412; Fax: +82-2-742-7344; E-mail: khcho@snu.ac.kr
nonspecific damage of normal cells by cytotoxic agents,
targeted agents have been developed and are increasingly used;
however, the most widely used targeted agents are epidermal
growth factor receptor (EGFR) inhibitors, which notoriously
induce acneiform rash in ∼45%–100% [1]. Skin lesions can
cause cosmetic problems leading to impairment in the quality
of life and poor patient compliance, more dose delays, and
even discontinuation of antineoplastic therapy [2, 3].

© The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com.