1060 Journal of Pain and Symptom Management Vol. 48 No.

6 December 2014

Original Article

Chemotherapy-Associated Oral Sequelae

in Patients With Cancers Outside the Head
and Neck Region
Petter Wilberg, DDS, Marianne J. Hjermstad, PhD, Stig Ottesen, PhD, MD, and
Bente Brokstad Herlofson, PhD, DDS
Department of Oral Surgery and Oral Medicine (P.W., S.O., B.B.H.), Faculty of Dentistry, University
of Oslo, Oslo; Regional Centre for Excellence in Palliative Care (M.J.H., S.O.), Department of
Oncology, Oslo University Hospital, Ullev
al, Oslo; and European Palliative Care Research Centre
(M.J.H.), Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Abstract
Context. Chemotherapy induces a wide array of acute and late oral adverse
effects that makes symptom alleviation and information important parts of patient
care.
Objectives. To assess the prevalence and intensity of acute oral problems in
outpatients receiving chemotherapy for cancers outside the head and neck region
and to investigate if information about possible oral adverse effects was received
by the patients.
Methods. In this cross-sectional study, outpatients aged 18 years or older were
invited to participate and included if they fulfilled the inclusion criteria. All
patients completed the Edmonton Symptom Assessment System, participated in a
semistructured interview, and underwent an oral examination by a dentist.
Results. Of 226 eligible patients, 155 (69%) participated. Mean age was
57 years, and 34% were males. The most prevalent diagnoses were breast (45%)
and gastrointestinal cancers (37%). Xerostomia was reported by 59%, taste
changes by 62%, oral discomfort by 41%, and 27% had problems eating. Fatigue
(3.4) and xerostomia (3.1) received the highest intensity scores on the Edmonton
Symptom Assessment System. Oral candidiasis confirmed by positive cultures was
seen in 10%. Twenty-seven percent confirmed that they had received information
on oral adverse effects of cancer treatment.
Conclusion. Oral sequelae were frequently reported, and health care providers
should be attentive to the presence and severity of these problems. Less than one-
third of the patients remembered having received information about oral
sequelae associated with chemotherapy. A continuous focus on how to diagnose,
manage, and inform about oral cancer-related complications is advisable. J Pain
Symptom Manage 2014;48:1060e1069. Ó 2014 American Academy of Hospice and
Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Address correspondence to: Bente Brokstad Herlofson, P.O. Box 1109, Blindern, NO-0317 Oslo, Norway.
PhD, DDS, Department of Oral Surgery and Oral E-mail: b.b.herlofson@odont.uio.no
Medicine, Faculty of Dentistry, University of Oslo, Accepted for publication: March 10, 2014.

Ó 2014 American Academy of Hospice and Palliative 0885-3924/$ - see front matter
Medicine. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpainsymman.2014.02.009
Vol. 48 No. 6 December 2014 Oral Problems Associated With Chemotherapy 1061

Key Words
Neoplasms, drug therapy, oral health, health literacy, xerostomia, mucositis

Introduction treated for other cancer diagnoses. Further-

more, personnel with special training in oral
Modern antineoplastic therapy for cancers
or dental care are not routinely included in
outside the head and neck area includes a
the hospital oncology teams in Norway.
wide spectrum of classic, novel, and targeted
The Edmonton Symptom Assessment Sys-
chemotherapeutic medications, all of which
tem (ESAS) is designed for quantitative assess-
can be highly bioactive. These drugs have a
ment of symptom intensity with minimal
broad spectrum of biological effects,1 such as
patient burden and is among the most
a suppressing effect of the bone marrow, the
frequently used symptom assessment tools in
epithelium of the oral cavity, and the salivary
cancer research, clinical care, and palliative
glands.1,2 In addition, antineoplastic therapy
care.16,17 The ESAS form used in this study
and medications used for symptom relief in
was a modified Norwegian version frequently
cancer patients are known to have adverse ef-
used in cancer hospitals in Norway at the
fects that may severely impact oral health and
time of the study to screen for cancer symp-
well-being.1e3 Many of these medications have
toms.18 It differs from the original by
no declaration of oral adverse effects in avail-
including two additional items, one regarding
able registers.3,4 A higher prevalence of caries
pain during movement and one regarding xe-
has been reported in a study that compared pa-
rostomia, but no open item.18 A cutoff value of
tients who had received chemotherapy with pa-
greater than 3 has been suggested to indicate
tients who had been treated with radiotherapy
symptoms calling for closer follow-up and
or chemoradiotherapy.5 However, this discrep-
perhaps tailored interventions.19,20
ancy was attributed to the differences between
The primary aim of this study was to assess
oral management regimens before radio-
self-reported and clinically manifest oral
therapy and chemotherapy.5
health problems during antineoplastic treat-
Most studies focus on single oral complica-
ment in patients treated for solid organ can-
tions of antineoplastic therapy such as salivary
cers outside the head and neck region by
gland hypofunction (objectively measured
means of the ESAS, a semistructured interview,
reduction of salivary flow and/or altered saliva
and an oral examination performed by a
composition),2,6 xerostomia (subjective feeling
dentist. Our secondary aim was to assess
of dry mouth),2,3,6,7 caries,5 infections,1,5,8e11
whether information regarding oral complica-
mucositis,1,12 altered sense of taste and smell,13
tions before or during treatment was received
or bisphosphonate-related osteonecrosis of the
by the patients.
jaws.14 There have been reports that such prob-
lems often are inadequately addressed in clin-
ical oncology settings.10,15 These problems
may lead to nutritional problems,9,10 impaired Methods
social function, and reduced quality of life1,10 Study Design
and require close cooperation between medi- This cross-sectional descriptive study was
cal and dental specialists regarding prevention, conducted at the Cancer Center, Oslo Univer-
diagnosis, and management. sity Hospital, Ullev

al, Norway, from February
Oral complications related to the disease 2005 to April 2007. Eligible patients were ap-
and/or the treatment of solid organ cancers proached by one of three attending dentists
outside the head and neck area are not well in the outpatient unit and invited to participate
documented.10 This may be a result of oral on one of the days they were scheduled to
sequelae being underreported by patients receive a chemotherapy cycle as part of their
and/or medical personnel.4,10 Head and overall chemotherapeutic treatment. Three
neck cancer patients often receive a standard- main elements were included in the study
ized oral health regimen in Norway, but such design: 1) patients completed the modified
regimens are seldom routine for patients Norwegian version of the ESAS, 2) a
1062
semistructured interview was conducted, and
3) a clinical oral examination was performed
by a dentist. These procedures were performed
once for each patient, on the day when the
dentist was on duty at the Cancer Center.
Study Population
A total of 226 outpatients receiving nonmye-
loablative chemotherapy for solid organ can-
cers outside the head and neck region were
approached for inclusion. The inclusion
criteria were as follows: 1) a diagnosis of cancer
outside the head and neck area, 2) receiving
curative or adjuvant chemotherapy at the
time of the study in an outpatient setting, 3)
age 18 years or older, 4) ability to provide
informed consent, and 5) cognitive and phys-
ical ability to undergo study procedures. Exclu-
sion criteria were as follows: 1) cancer in the
head and neck region, 2) radiation treatment
to a metastasis in the head and neck region,
and 3) not willing or able to undergo all parts
of the study protocol.
Interview and Questionnaire
A protocol based on a previous study on oral
discomfort in palliative care cancer patients
was used.4 The Norwegian version of the
ESAS was completed before the examination.
The Norwegian ESAS is slightly modified
from the original and includes 10 common
symptoms of cancer (pain at rest, pain when
moving, fatigue, nausea, dyspnea, xerostomia,
appetite, anxiety, depression, general well-be-
ing).16,18 All symptoms are scored on a 0e10
numerical rating scale, with higher scores
implying higher symptom intensity. The ESAS
scores were reported as mean values (SD)
and also dichotomized by using a cutoff of
greater than 3 according to proposed cutoff
scores with greater sensitivity when screening
for moderate to severe symptoms on the
ESAS.19 This cutoff is often used nationally
and internationally to indicate symptoms
requiring further assessment.19e22
The 62-item registration form used for the
semistructured interview included age, gender,
and anamnestic information, such as seven ques-
tions about tobacco and alcohol use, and 16
items about prior general/oral health problems
and habits. A further 14 items investigated
current problems in the oral cavity. Six items
assessed whether information about issues
Wilberg et al. Vol. 48 No. 6 December 2014
related to the oral cavity was received by the pa-
tient before and during treatment. Cancer diag-
nosis and treatment information was collected
from the patients’ medical chart. Most items
had dichotomous answer categories, but cate-
gorical variables were used as appropriate, for
example, weight loss. Karnofsky Performance
Status score23 was registered by the investigating
dentist. The number of chemotherapeutic cy-
cles received in their overall treatment regimen
was recorded. The total number of systemic
medications per patient was counted.
Clinical Oral Examination
The oral examination was performed by a
dentist in a hospital examination room in the
outpatient cancer clinic and included a system-
atic registration of findings on the oral mucosa,
teeth, and gingiva. Clinical expression of a
fungal infection was recorded according to Ax-
ell’s classification of oral candidiasis,24 and mu-
cositis was recorded according to the World
Health Organization classification.25 Total
number of remaining teeth was assessed. Pla-
que and gingiva were evaluated by the
mucosal-plaque index developed for evaluation
of oral health and oral hygiene in hospitalized
and nursing home patients.26 If oral treatment
was needed, the patient was informed and assis-
ted in contacting a hospital or a private dentist.
Oral mucosal swabs were taken for identifica-
tion of fungal carriage and inoculated on Sab-
ouraud’s dextrose agar for four days at 37
C. If
oral candidiasis was suspected clinically and
confirmed by culture, treatment was given in
collaboration with the attending physician.
Ethical Considerations
Ethical approval was obtained from the
Regional Committee for Medical Research
Ethics, Health Region South-Eastern Norway.
Data storage and conduct of the study were
performed according to the regulations set
forth by the Norwegian Data Inspectorate,
the Data Protection Supervisor, and the
Research Committee at Oslo University Hospi-
tal. Written informed consent was obtained
from all participants.
Statistical Analysis
IBM SPSS Statistics 20.0 for Windows (IBM
Corp., Armonk, NY) was used for data analysis.
Variables were described by means, SD, and
Vol. 48 No. 6 December 2014 Oral Problems Associated With Chemotherapy 1063

percentages. The dependent variable, oral

discomfort, was determined by the patients’
answer to the dichotomous question: ‘‘Do
you suffer from discomfort or pain from the
oral cavity at present?’’ For the univariate anal-
ysis, Chi-squared tests, t-tests, and analysis of
variance with a post hoc Tukey’s honest signif-
icant difference test were used as appropriate.
The factors that were statistically significantly
associated (<0.05) with oral morbidity in the
univariate analysis were entered as predictors
in a multivariate logistic regression analysis us-
ing forward variable selection. All variables
entered in the multivariate analysis had vari-
ance inflation factors below five. Generally
for ESAS, the significant dichotomous vari-
ables showing ESAS greater than 3 were
selected for inclusion in the multivariate anal-
ysis as they are considered to represent moder-
ate to severe symptoms.19,20 The ESAS
xerostomia score of greater than 3 was chosen
as the variable to represent mouth dryness Fig. 1. Flowchart of patient inclusion.
because it indicates self-reported symptoms
requiring further assessment20 and was the study population reported xerostomia at the
first item regarding xerostomia to be time of the examination (Table 1), and 38%
answered. Therefore, we considered it less (n ¼ 58) said they had suffered from this for
likely to be biased by the multiple subsequent more than three months. Taste changes were re-
questions regarding oral health included in ported by 62% (n ¼ 96) of the patients, and 27%
the patient interview. A P-value of 0.05 or less (n ¼ 42) had problems eating. During the past
was taken to indicate statistical significance. six months, 25% (n ¼ 39) of the patients had
lost more than 5 kg of bodyweight (Table 1). Xe-
rostomia (82%, n ¼ 52) and taste changes (75%,
Results n ¼ 48) were the most frequently reported oral
symptoms in the discomfort group (Table 1).
Study Population
A total of 168 (74%) of the 226 eligible pa-
tients agreed to participate, and 155 (69%) Clinical Findings
completed the entire study (Fig. 1). The At the time of examination, microbial evi-
mean age of the study population was dence of candida carriage was found in 72%
57.0 years (SD 11.8), 67% (n ¼ 103) were fe- (n ¼ 109) of the patients. Ten percent
males, and the mean number of weeks since (n ¼ 16) had both clinical and microbiological
diagnosis was 88 (SD 102) (Table 1). Mean Kar- evidence of oral candidiasis (Table 1). Five of
nofsky Performance Status score was 74.7 (SD the patients with both clinical and microbio-
14.7). All patients had solid organ cancers, logical evidence of oral candidiasis were
with breast (45%, n ¼ 69), gastrointestinal already receiving antifungal treatment. Muco-
(37%, n ¼ 58), and prostate cancer (7%, sitis grade 3e4 was not found, but 12%
n ¼ 10) being the most prevalent diagnoses. (n ¼ 18) of the patients had Grade 1e2. Six pa-
Most patients (85%, n ¼ 131) had regionally tients used partial or complete dentures, and
advanced and/or metastatic disease (Table 1). 96% (n ¼ 147) of all patients had 17 teeth or
more, with 28 considered a full dentition.
Patient Interview Moderate or rich amounts of dental plaque
Oral discomfort was reported by 41% (n ¼ 64) were seen in 33% (n ¼ 51) of patients
of the patients. Fifty-nine percent (n ¼ 92) of the (Table 1).
1064 Wilberg et al. Vol. 48 No. 6 December 2014

Table 1
Patient Characteristics and Clinical Symptoms Related to Oral Discomfort
Reported Oral Discomfort

Total Yes No

Variable n ¼ 155 n ¼ 64 (41%) n ¼ 91 (59%) P-value

Patient characteristics
Age, mean (SD) 57.0 (11.8) 55.3 (12.1) 58.2 (11.5) 0.13
Female, N (%) 103 (67) 47 (73) 56 (62) 0.12
Weeks since diagnosis, mean (SD) 88 (102) 77 (85) 97 (112) 0.23
Smoker, N (%) 23 (15) 13 (20) 10 (11) 0.11
Karnofsky score > 40, N (%) 151 (97) 62 (97) 89 (98) 0.72
Regionally advanced, metastatic, or generalized disease, N (%) 131 (85) 52 (83) 79 (87) 0.46
Patient interview, N (%)
Xerostomia 92 (59) 53 (82) 39 (43) <0.001b
Taste changes 96 (62) 48 (75) 48 (53) 0.006a
Problems eating 42 (27) 26 (41) 16 (18) 0.002a
Lost >5 kg last 6 months 39 (25) 21 (33) 18 (20) 0.07
Clinical findings, N (%)
Candidiasis 16 (10) 12 (19) 4 (4) 0.004a
Mucositis grade 1e2 18 (12) 12 (19) 6 (7) 0.02a
Moderate or rich amount of dental plaque 51 (33) 16 (25) 35 (39) 0.09
Moderate inflammation of gingiva 22 (14) 8 (13) 14 (15) 0.64
Chemotherapy and medications, mean (SD)
Chemotherapeutic cycles 8.2 (7.7) 8.3 (6.5) 8.2 (8.6) 0.95
Number of systemic drugs 5.8 (2.5) 6.4 (2.6) 5.3 (2.4) 0.01a
a
P < 0.05.
b
P < 0.001.

Chemotherapy and Medication also received significantly more systemic medica-

The mean number of antineoplastic cycles
received before the study was 8.2 (SD 7.7)
(Table 1). There was no significant difference
in the mean number of cycles between those
who reported oral discomfort and those who
did not (P ¼ 0.95) (Table 1). There was a signif-
icant difference in the total number of systemic
drugs used (6.4 [SD 2.6] vs. 5.3 [SD 2.4];
P ¼ 0.01), with patients reporting oral discom-
fort taking more medications than patients who
did not experience oral discomfort (Table 1).
Most patients (62%) received fluorouracil (5-
FU)-based regimens (Table 2). There was a signif-
icantly lower proportion of patients receiving
FEC (5-FU, epirubicin, and cyclophosphamide)
therapy who reported taste alterations compared
with the other treatment regimens (41% vs. 68%,
P ¼ 0.004) (Table 2). A larger portion of patients
receiving FLOX (5-FU, leucovorin, and oxalipla-
tin) experienced problems eating (47% vs. 22%,
P ¼ 0.005), mucositis (25% vs. 8%, P ¼ 0.008),
and candidiasis (25% vs. 7%, P ¼ 0.002)
compared with patients receiving other treat-
ment regimens (Table 2). Patients on FEC,
FLOX, and taxane regimens received a signifi-
cantly higher number of systemic drugs than
patients on regimens not including 5-FU or tax-
anes. The patients on FEC or FLOX regimens
tions than those on other 5-FU regimens. Patients
on taxane-based regimens had received a signifi-
cantly higher number of chemotherapeutic
cycles (mean 20.3, SD 13.7, P < 0.001) and had
lived longer with their cancer diagnosis
(186 weeks, SD 128, P < 0.001) than patients
receiving other treatment regimens (Table 2).
Intravenous bisphosphonate therapy was used
in 12% (n ¼ 19) of the patients, but no case of os-
teonecrosis of the jaw was seen.
Edmonton Symptom Assessment System
The highest mean scores on the ESAS in all
patients were found for fatigue (mean 3.4, SD
2.5) and xerostomia (mean 3.1, SD 2.9)
(Table 3). A significantly larger proportion of
the patients who reported oral discomfort
scored greater than 3 on ESAS xerostomia
than those who did not (61% vs. 21%;
P < 0.001) (Table 3). Patients who reported
oral discomfort also reported a significantly
higher mean intensity on the ESAS xerostomia
item than those who did not (4.7, SD 2.6 vs.
1.9, SD 2.5; P < 0.001) (Table 3).
Information
Seventy-three percent (n ¼ 112) of the pa-
tients stated that they had not received any
Vol. 48 No. 6 December 2014 Oral Problems Associated With Chemotherapy 1065

Table 2
Characteristics and Adverse Oral Symptoms Related to Different Chemotherapeutic Regimens, N ¼ 155
FEC With FLOX With Taxanes With Other Regimens
Miscellaneous Miscellaneous Other 5-FU Miscellaneous Than 5-FU and
Drugs Drugs Regimens Drugs Taxanes

n ¼ 35 n ¼ 32 n ¼ 29 n ¼ 25 n ¼ 34
Variable (23%) (21%) (19%) (16%) (22%)

Patient characteristics
Age, mean (SD) 51.0 (9.6)a 55.3 (11.3) 63.3 (11.6)a 59.3 (12.8) 57.7 (11.1)
Female, n (%) 33 (94)b 15 (47) 12 (41) 16 (64) 27 (80)
Patient interview, n (%)
Oral discomfort 17 (49) 16 (50) 10 (35) 10 (40) 11 (32)
Xerostomia 21 (60) 18 (56) 20 (69) 14 (56) 19 (56)
Taste changes 14 (41)a 23 (72) 20 (69) 19 (76) 20 (59)
Problems eating 6 (18) 15 (47)a 8 (28) 7 (28) 6 (18)
Clinical findings, n (%)
Mucositis 4 (11) 8 (25)a 3 (10) 2 (8) 1 (3)
Candidiasis 3 (9) 8 (25)a 4 (14) 0 (0) 1 (3)
ESAS, n (%)
ESAS xerostomia >3 10 (29) 16 (50) 14 (48) 8 (32) 10 (29)
ESAS appetite >3 6 (17) 9 (28) 12 (41) 8 (32) 9 (27)
Treatment, mean (SD)
Number of systemic drugs 6.7 (1.8)a 7.4 (1.8)a 4.9 (2.6) 6.0 (2.4) 3.7 (2.3)a
Number of chemotherapeutic cycles 5.3 (3.9) 6.6 (5.0) 7.4 (3.9) 20.3 (13.7)a 8.6 (7.7)
Number of weeks since diagnosis 51 (72) 60 (76) 50 (51) 186 (128)a 88 (110)
FEC ¼ 5-FU, epirubicin, and cyclophosphamide; FLOX ¼ 5-FU, leucovorin, and oxaliplatin; 5-FU ¼ fluorouracil; ESAS ¼ Edmonton Symptom
Assessment System.
a
P < 0.05 compared with patients receiving the other treatment regimens.
b
P < 0.001 compared with patients receiving the other treatment regimens.

information about possible oral adverse effects about the importance of maintaining good
related to cancer and cancer treatment before oral hygiene during treatment. A significantly
or during therapy, whereas 30% (n ¼ 45) had higher proportion of the patients who re-
received information about how to reduce xe- ported oral discomfort also reported that
rostomia. Of the 92 (59%) patients reporting they were not satisfied with the information
xerostomia as a problem, 34% (n ¼ 31) said received before and during their treatment
that they had received such information. compared with those without oral discomfort
Only 27% (n ¼ 42) had received information (35.9% vs. 19.8%, P ¼ 0.03).

Table 3
Symptom Intensity Assessed by the ESAS, in Patients With or Without Oral Discomfort
Symptom Intensity Percentage With Symptom Intensity >3

Self-Reported Oral Self-Reported Oral

Discomfort Discomfort
ESAS All
Patients Yes (n ¼ 64); No (n ¼ 91);
(n ¼ 155); Yes (n ¼ 64); No (n ¼ 91); Percent With Percent With Percent With
ESAS Symptom Mean (SD) Mean (SD) Mean (SD) P-value Symptom >3 Symptom >3 Symptom >3 P-value
a
Pain at rest 1.4 (2.1) 1.8 (2.3) 1.1 (1.9) 0.04 15 21 11 0.11
Pain when moving 2.0 (2.6) 2.6 (2.8) 1.6 (2.3) 0.02a 24 31 19 0.07
Fatigue 3.4 (2.5) 4.1 (2.3) 2.9 (2.5) 0.004a 48 59 41 0.02a
Nausea 1.4 (2.1) 2.3 (2.4) 0.8 (1.7) <0.001b 15 27 7 0.001a
Dyspnea 2.0 (2.5) 2.1 (2.6) 1.9 (2.5) 0.51 25 25 24 0.94
Xerostomia 3.1 (2.9) 4.7 (2.6) 1.9 (2.5) <0.001b 37 61 21 <0.001b
Appetite 2.4 (2.8) 2.9 (2.7) 2.0 (2.8) 0.05a 28 36 23 0.08
Anxiety 1.9 (2.3) 2.3 (2.4) 1.7 (2.2) 0.07 21 28 17 0.09
Depression 1.6 (2.1) 1.9 (2.5) 1.3 (1.8) 0.08 15 20 11 0.11
General well-being 2.4 (2.3) 3.2 (2.3) 1.7 (2.1) <0.001b 29 44 19 0.001a
ESAS ¼ Edmonton Symptom Assessment System.
a
P < 0.05.
b
P < 0.001.
1066 Wilberg et al.
Multivariate Analysis
The significant factors associated with oral
discomfort in the univariate analysisdtotal
number of systemic medications, problems
eating, taste changes, candidiasis, mucositis,
and ESAS score greater than 3 on fatigue,
nausea, xerostomia, and general well-beingd
were entered as predictors in a multivariate lo-
gistic regression analysis using forward variable
selection. The multivariate analysis showed
that ESAS xerostomia greater than 3
(P < 0.001), mucositis (P ¼ 0.03), and a higher
number of systemic medications (P ¼ 0.03)
were significantly associated with more oral
discomfort.
Discussion
The present study showed that oral sequelae
are common in patients treated for cancers
outside the head and neck area. In the multi-
variate analysis, oral discomfort was signifi-
cantly associated with patient-reported ESAS
xerostomia scores greater than 3, the presence
of oral mucositis, and using a high number of
medications.
In this study, the prevalence of mucositis
grade 1e2 was 12%, and no patients suffered
from mucositis grade 3e4. This is lower than
figures previously reported by the mucositis
section of the Multinational Association of
Supportive Care in Cancer/International Soci-
ety of Oral Oncology in their review of cancer-
induced mucosal injuries.1 In their overview,
the incidence of World Health Organization
mucositis grade 3e4 was between 3% and
18% for chemotherapeutic regimens
described in our study. This discrepancy may
be a result of our study design. We recorded
mucositis before infusion of antineoplastic
medications. In a cross-sectional study, this
does not necessarily correspond to when the
patients experience the highest level of
toxicity. Toxicity also may vary throughout a
course of treatment with different agents. In
the interview, some patients reported that
they had experienced more severe oral ulcera-
tions before our examination. However, muco-
sitis grade 1e2 was significantly associated with
the patients’ self-reported perception of oral
discomfort at the time of examination in the
multivariate analysis. In our opinion, this
Vol. 48 No. 6 December 2014
emphasizes the need to increase the awareness
of this problem during chemotherapy and
inform the patients about preventive measures
and pain-relieving interventions.
In a systematic review from 2010, Jensen
et al.6 described a prevalence of xerostomia
of 50% during chemotherapy. In the present
study, 59% of the patients experienced xero-
stomia at the time of examination, with 37%
grading it as greater than 3 on the numerical
ESAS scale. Xerostomia greater than 3 on the
ESAS was significantly associated with patient-
perceived oral discomfort in the multivariate
analysis, and xerostomia had the highest symp-
tom intensity score on the ESAS among pa-
tients reporting oral discomfort. This may
indicate that oncology teams have a greater
focus on alleviation of other cancer- and
treatment-related symptoms, for example,
pain, nausea, depression, and dyspnea.
Furthermore, physicians and nurses have little
training in recognizing, diagnosing, and man-
aging oral complications, and education in
recognition and treatment of oral complica-
tions is advisable for oncology nurses and phy-
sicians. Oral health personnel are seldom
included in oncology teams managing patients
with cancers outside the head and neck in Nor-
way, but it would be preferable if personnel
with experience in cancer-related oral health
problems were included as an integral part of
the oncology team.
The number of systemic medications influ-
enced the patients’ perception of oral discom-
fort as a higher number of medications
predicted more oral discomfort, also seen in
the multivariate analysis. Many drugs used in
cancer therapy and in alleviation of symptoms
related to cancer and cancer treatment are
known to induce hyposalivation, mucositis,
taste alterations, and other sequelae. A high
number of medications should make health
personnel attentive to oral adverse effects
and may be an indicator of when to involve
oral health personnel in the follow-up of
patients.
Our data suggest that significantly fewer pa-
tients receiving FEC chemotherapy regimens
experienced taste changes than patients
treated with other regimens. This is in contrast
to the findings by Bernhardson et al.13 who
showed that FEC chemotherapy had the
same risk of taste and smell disturbances as,
Vol. 48 No. 6 December 2014 Oral Problems Associated With Chemotherapy
for example, FLOX. They concluded that taste
and smell changes were common problems
during chemotherapy, but that sociodemo-
graphic factors were more related to the prob-
lem than to the treatment regimens per se.
However, we did not assess smell disturbances,
which may explain some of this discrepancy.
Other explanations might be that the study
sample size was small, almost all patients
receiving FEC in our study were females, and
concurrent medications may differ. Patients
receiving FLOX regimens had more problems
with mucositis, candida infections, and eating
than patients on other regimens. Sonis et al.1
reported a higher risk of Grade 3e4 mucositis,
for example, docetaxel (a taxane) (13%) than
for FLOX regimens. This discrepancy may be
explained by when in the overall chemothera-
peutic regimen our examination was conduct-
ed and possible different treatment modalities
between our study and the studies reported in
the review. We found that patients on taxane-
based regimens had lived significantly longer
with their diagnosis and had received a higher
number of chemotherapeutic cycles. The most
likely explanation is that anthracycline-based
regimens are considered to be the first-line
chemotherapeutic treatment option in breast
cancer patients in Norway, whereas taxane-
based regimens are most often used as second-
or third-line regimens.
Most of the study population claimed not
to have received information about means
to reduce xerostomia, potential oral adverse
effects of treatment, or how to maintain
proper oral hygiene during treatment. This
is in line with a previous study from our
group, demonstrating a lack of information
among palliative care cancer patients.4 How-
ever, this was an unexpected finding as all
cancer patients who come for scheduled
chemotherapy have a consultation with an
oncologist before start of the treatment, and
receive an information booklet from the
department. This booklet contains, among
other information, a description of oral symp-
toms such as soreness of the mucosa, mucosi-
tis, and xerostomia including management
strategies. This suggests that oral information
early in the disease process and written
educational material are not necessarily suffi-
cient to make patients retain this informa-
tion. A continuous focus on oral adverse
1067
effects and management strategies
throughout the cancer treatment is advisable.
Furthermore, simple assessment tools for oral
side effects, such as the new European Orga-
nization for Research and Treatment of Can-
cer oral health module, the QLQ-OH17
(Quality of Life Questionnaire-Oral Health
17),27 may help increase the awareness
among health care providers, identify pa-
tients who may need specialized oral care,
and as such, prevent more profound side
effects.
One limitation of the present study was the
higher proportion of females, which does not
reflect the gender distribution of cancer inci-
dence (male 54%) in Norway.28 This was
most likely a result of an allocation of certain
cancer diagnoses, for example, testicular and
breast cancer, to different hospitals within
the region at the time of the study. However,
we found no indication that oral adverse ef-
fects affect women more than men. The
cross-sectional design as opposed to a prospec-
tive design and the lack of control group may
be viewed as a limitation as this does not
permit comparisons over time or with healthy
subjects.
The diversity of the study population with re-
gard to age, diagnosis, time since diagnosis,
and chemotherapeutic treatment regimens
may be regarded both as a limitation and a
strength of the study. This limited the possibil-
ity of investigating differences across sub-
groups. However, the study may indicate
patient groups of interest to follow in future
longitudinal studies, such as patients receiving
FEC or FLOX regimens. This would enable us
to evaluate the development of different oral
adverse effects over time, implement preven-
tive measures, and give specific information
at the right time.
A major strength of the present study is the
mixed methods, with self-report, an interview
and an oral examination performed by a
dentist. Another factor is that all concurrent
systemic medications were recorded alongside
the chemotherapeutic regimens. Concurrent
medication may be one of the several factors
that may explain why patients receiving the
same chemotherapeutic regimen experience
oral morbidity differently. Therefore, we
believe that the combination of patient self-
report of symptoms, interview disclosing
1068
additional information, and the clinical
examination provide important information
regarding oral problems in cancer outpatients
treated with chemotherapy.
Conclusion
Outpatients receiving chemotherapy for
solid organ cancers outside the head and
neck region experienced several oral sequelae,
most notably xerostomia and mucositis, that
were predicted by a high quantity of concur-
rent systemic medications. Xerostomia was
rated significantly higher than all other
commonly experienced symptoms of cancer
treatment. Most patients had not received in-
formation about oral complications or oral
care before treatment. A continuous focus on
how to inform, diagnose, and manage oral
cancer-related complications would be advis-
able. Oral health care personnel should be
an integral part of oncology teams.
Disclosures and Acknowledgments
This study received financial support from
the Norwegian Cancer Society, grant number
59030001. The authors thank them for the
gracious support of their research. The au-
thors do not have any financial benefits or con-
flicts of interest that might bias this work.
The authors thank Professor Leiv Sandvik
for his help with the statistics, Professor Nina
Aass for her help with oncology questions,
and collaborating dentists Kristine Løken and
Margareth Kristensen for their help during
data collection.
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