R&D INSIGHTS

One of the most uncomfortable consequences of anticancer therapy is the development of 

oral mucositis. This painful condition develops in approximately 40% of patients treated with 

standard chemotherapy, 30%–60% of patients receiving radiation therapy for cancer of the head 

and neck, 70% of patients who undergo bone marrow transplantation and receive high-dose chemo- 

therapy, and over 90% of patients receiving concomitant 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 associated 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 hospitalization 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 preventive/educational
measures be given to reduce the risk of developing mucositis or to reduce the severity of mucositis. Key educational
material should include 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 inflammation (anti-inflammatory). One treatment option 

that has proven to be safe and effective at reducing 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.  After 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 significantly
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 Caphosol “should be considered in the treatment of of 

patients undergoing hematopeoitic stem-cell transplantation 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 patients 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, every 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 chemotherapies
for solid tumors, bone marrow transplant, and radiation for head and neck cancer will 

develop oral mucositis, it is advised that these patients be part of an oral hygiene plan that cleans 

the oral cavity and promotes healing of the mucosal 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 

days of pain (P < .0001) and days of morphine use (P < .00015) compared 

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