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One of the most uncomfortable consequences of anticancer therapy is the development of oral mucositis.
INSIGHTS
R&D
One of the most uncomfortable consequences of anticancer therapy is the development of
oral mucositis. This painful condition devel
ops in approximately 40% of patients treated with
standard chemotherapy, 30%—60% of patients re
ceiving radiation therapy for cancer of the head
and neck, 70% of patients who undergo bone mar
row transplantation and receive high-dose chemo-
therapy, and over 90% of patients receiving con
comitant chemotherapy and localized radiation. (1)
Oral mucositis is characterized by erythema,
swelling, and ulceration of the mucous membranes.
The consequences of this inflammation can greatly
affect a patient’s health, quality of life, and antican-
cer therapy outcome. The disruption of the natural
mucosal barrier can increase the risk of systemic
infections. Furthermore, the intense pain associ
ated with oral mucositis may impede the patient’s
eating and oral hygiene activities which in turn can
disrupt the efficacy of cancer therapy.
The economic consequences of oral mucositis
are substantial. In patients receiving high-dose
chemotherapy for
stem-cell transplant, Sonis and
colleagues (2) observed that the increased infections,
disruption of therapy, and
increased need for hospi
talization caused by oral mucositis added $43,000
per patient. Costs were also dependent
on the level
of oral mucositis. The authors estimated that for
each 1 point rise in the oral mucositis assessment
scale (OMAS), there was an additional $25,000 in
costs. Similarly, in patients treated with standard-
dose chemotherapy,
a large portion of the extra
costs of mucositis arise from the increased need for
hospitalization. (3)
Management of Oral Mucositis
The best management option for oral mucositis
however, is preventive therapy—a key component
of which is recognizing which patients are at risk.
Once it is established that the patient will likely
develop oral mucositis, it is imperative that preven
tive/educational
measures be given to reduce the
risk of developing mucositis or to reduce the sever
ity of mucositis. Key educational
material should in
clude the importance of oral hygiene to reduce the
risk of inflammation and nutritional advice to
help
the patient get the calories needed during therapy
while reducing the discomfort of mucositis.
If the patient does develop oral mucositis, most
treatment options are symptomatic to reduce pain
(analgesic), swelling (cryotherapy), and/or inflam
mation (anti-inflammatory). One treatment option
that has proven to be safe and effective at reduc
ing the incidence, severity, and duration of oral
mucositis is Caphosol®
(Supersaturated Calcium
Phosphate Rinse).
Caphosol
Caphosol is a super-saturated Ca2+/PO42- solution
and is believed to promote healing of the mucosal
lesions while helping to cleanse the oral cavity.
In this manner, it reduces both the intensity and
duration of mucositis in patients given high-dose
chemotherapy. This was observed in a prospective,
double-blind, randomized clinical trial by Papas
and colleagues5 who compared Caphosol used at
the initiation of cancer therapy in conjunction with
proper oral hygiene with standard fluoride rinse
in 95 patients undergoing hematopoietic stem-cell
transplantation. During the course of treatment,
oral mucositis was scored on a 6 point scale (0-no
change; 1-erythema; 2-single ulcer < 1 cm; 3-a few
ulcers approximately 1 cm; 4-multiple ulcers < 1
cm; 5-slough) and pain on a 0—100 visual analog
scale (VAS). Inflammation (absolute neutrophil
counts) and morphine intake were also measured
during the study.
One interesting aspect of this study was that it
acknowledged the importance of oral hygiene be-
fore beginning bone marrow transplant. Before
transplant, patients in the Caphosol group received
Caphosol and four topical fluoride treatments. Af
ter the transplant they received Caphosol at least
four times daily. The comparator group was given
a placebo gel with fluoride rinse prior to transplant
and the fluoride rinse continued after transplant (at
least 4 times daily).
The results of this study were very encouraging.
As shown in Figure 1, the mean number of days
patients experienced mucositis (days with score
> 1) or ulcerations were significantly lower in pa-
tients receiving Caphosol compared with standard
fluoride care. Patients given Caphosol also had sig
nificantly
fewer days of pain and fewer days that
required morphine (Figure 2). Further analysis
showed the patients
receiving Caphosol had fewer
days of neutrophil engraftment, lower peak levels
of mucositis and lower peak levels of pain.
The authors of this study concluded that Capho
sol “should be considered in the treatment of of
patients undergoing hematopeoitic stem-cell trans
plantation at high risk for mucositis.” The authors
also noted that the encouraging results seen in this
study with bone marrow transplant patients were
similar to results reported at conferences with pa
tients undergoing radiation and/or chemotherapy.
Concluding Remarks
Oral mucositis is a costly consequence of cancer
therapy that can impede the efficacy of anticancer
therapy. Even small reductions in OMAS scores can
reduce medical costs by the thousands while im-
proving the patient’s quality of life. Therefore, ev
ery effort to reduce the severity and/or risk of get-
ting mucositis should be undertaken by the patient
as well as the patient’s oncologist, general practitio-
ner, dentist, and other medical professionals.
Since most patients undergoing high-dose che
motherapies
for solid tumors, bone marrow trans
plant, and radiation for head and neck cancer will
develop oral mucositis, it is advised that these pa
tients be part of an oral hygiene plan that cleans
the oral cavity and promotes healing of the mu
cosal lesions. Using these simple preventive mea-
sures, the patient’s outcome and quality of life can
greatly improve.
Patient Related
Treatment Related
Risk factors for mucositis include4
Age (children and patients over 50 yr of age)
Female sex
Tumor location (e.g., oral cavity, throat)
Pre-existing mouth damage
Periodontal status
Tobacco and alcohol consumption
Genetic predisposition
Chemotherapy (type of drug, dose and intensity,
induced neuropenia)
Radiotherapy (location, fractioning,
combined with chemotherapy)
Bone marrow transplantation
References
1. Naidu MUR, Ramana GV, Rani PU, et al: Chemotherapy-
induced and/or radiation therapy—induced oral mucosi-
tis—Complicating the treatment of cancer. Neoplasia
2004;6:423-431.
2. Sonis ST, Oster G, Fuchs H, et al: Oral mucositis and the
clinical and economic outcomes of hematopoietic stem-cell
transplantation. J Clin Oncol 2001;19:2201-2205.
3. Elting LS, Cooksley C, Chambers M, et al: The burdens of
cancer therapy: Clinical and economic outcomes of chemo-
therapy-induced mucositis. Cancer 2003;98:1531-1539.
4. D’Hondt L, Lonchay C, Andre M, et al: Oral mucositis induced
by anticancer treatments: Physiopathology and treatments.
Ther Clin Risk Manag 2006;2:159-168.
5. Papas AS, Clark RE, Martuscelli G, et al: A prospective, ran-
domized trial for the prevention of mucositis in patients
undergoing hematopoietic stem cell transplantation. Bone
Marrow Transplant 2003;31:705-712.
Figure 1. The Caphosol group had a statistically significant lower mean
days of mucositis (P < .00096) and days of ulceration (P < .00019) com-
pared with the fluoride-rinse group.5
Figure 2. The Caphosol group had a statistically significant lower mean
< .00015) compared
days of pain (P < .0001) and days of morphine use (P
with the fluoride-rinse group.5
Days (mean) of
mucositis Days (mean) of painDays (mean) of ulceration Days (mean) of morphine
Caphosol
Flouride
Caphosol
Flouride