Sorensen, J. B., Skovsgaard, T., Bork, E., Damstrup, L., & Ingeberg, S. (2008). Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil–based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies. Cancer, 112(7), 1600–1606.

Intervention Characteristics/Basic Study Process

Randomized after consent to one of three arms (A, B, or C)

A = chlorhexidine mouthwash (0.1% without alcohol, 10 ml) with taste additives

B = placebo mouthwash (normal saline) with taste additives  

C = crushed ice

Participants were stratified according to age (older than 40 versus younger than 40), smoking or nonsmoking, and use of dental prosthesis. Patients and the physician were blinded with respect to mouthwash versus placebo.

Both rinses were administered for 1 minute TID on days 1–21; crushed ice was administered from 10 minutes before until 35 minutes after the start of chemotherapy.

Sample Characteristics

Study sample included patients with gastric or colorectal cancer receiving bolus 5-FU 425 mg/m2 and bolus leucovorin 20 mg/m2 (Mayo regimen) for five days every four weeks.

Exclusion criteria were head and neck radiotherapy and symptoms of infections.

 
Arm A: n = 73
Arm B: n = 66
Arm C: n = 67

 

Measurement Instruments/Methods

Patients were evaluated when they returned for the second round of treatment on day 28.
 
Patients were evaluated on days 14 and 28. Signs and symptoms from the oral cavity were observed and registered on a daily basis and written into the questionnaires on days 14 and 28.

The treating physician evaluated patients on days 14 and 28 using the NCI Common Toxicity Criteria (CTC).
 

Results

No differences were observed in compliance with regimen or side effects (e.g., headache, taste disturbances).
 
Twenty-three percent of patients in arm B and 43% of patients in arms A and C had no mucositis.

Of the three arms, only one patient had grade 4 mucositis (arm A).
The frequency of grades 3 and 4 were 12% in arm A, 32% in arm B, and 10% in arm C. Frequency was significantly lower in arm A (p < 0.01) and arm C (p < 0.005) compared with arm B. Arms A and C were similar.

No differences were observed between patient or physician scoring.

Median duration of oral mucositis was 3 days (arm A), 5 days (arm B), and –1 day (arm C). Duration was significantly shorter in arm B than in arm A (p = 0.035) and arm C (p = 0.003). No differences were observed between arms A and C.

Neither smoking nor performance status predicted severity of oral mucositis.

Ages were unequal across arms but not statistically different.
 

Limitations

Power analysis of 15%; decreased CTC mucositis grade 3–4; 75 patients in each arm. The study had 225 evaluable participants, but not all participants returned forms.

Two arms were double blinded. Cryotherapy could not be double blinded but was blind to MD assessment.