Managing Oral Mucositis in Patients With Cancer

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