Phenylbutyrate Mouthwash

Phenylbutyrate Mouthwash

PEP Topic 

Phenylbutarate is a chemical compound that is a type of gene modulator that can reduce oxidative stress induced tissue damage and is currently an approved drug for urea cycle disorder. A mouth rinse containing phenylbutarate was studied for its effects on mitigating oral mucositis in patients with cancer.

Effectiveness Not Established

Research Evidence Summaries

Yen, S. H., Wang, L. W., Lin, Y. H., Jen, Y. M., & Chung, Y. L. (2012). Phenylbutyrate mouthwash mitigates oral mucositis during radiotherapy or chemoradiotherapy in patients with head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics, 82(4), 1463-1470.


Study Purpose:

To determine the therapeutic safety and efficacy of phenylbutyrate (an antitumor histone deacetylase inhibitor and chemical chaperone) 5% mouthwash for treating oral mucositis caused by cancer therapy.  

Intervention Characteristics/Basic Study Process:

One group received standard oral care plus 5 ml of phenylbutyrate 5% mouthwash (swish and spit) applied four times daily; the other group received standard oral care plus 5 ml of placebo that contained the same base of mouthwash but no phenylbutyrate.

Sample Characteristics:

The study was comprised of 31 patients (14 in the phenylbutyrate group and 17 in the placebo arm), age 20 years or older.

MALES (%) 11 treatment and 17 placebo, FEMALES (%) 6 treatment and 2 placebo




SITE: Multi-site

SETTING TYPE: Both inpatient and outpatient

LOCATION: Two medical centers in Taiwan

Phase of Care and Clinical Applications:

PHASE OF CARE: Active treatment

APPLICATIONS: Elderly care, end of life, and palliative care

Study Design:


Measurement Instruments/Methods:

  • WHO mucositis score    
  • Oral Mucositis Assessment Scale ulceration score
  • Duration of OM


Study showed that at cumulative doses below 5,000 cGy, the WHO mucositis score and the mean OMAS ulceration scores were relatively low between both groups.  However, at cumulative doses above 5,000 cGy, the severity of the mucositis and ulceration increased in the placebo group and decreased in the phenylbutyrate group. From 5,500 to 7,500 cGy, the phenylbutyrate group showed a statistically significant decrease in the severity of mucositis (WHO p = 0.0262, OMAS ulceration score p = 0.049). At a cumulative RT dose of 6,000-7,000, the intensity of ulceration was significantly lower in patients that received phenylbutyrate. The median duration of symptomatic mucositis was 16 days in the control group and 50 days in the placebo group. Endpoints included safety and efficacy.


Phenylbutyrate benefited patients by reducing the risk of severe mucositis by 24% and decreasing extensive ulceration by 61%; this was accomplished by shortening the duration of severe mucositis and promoting wound healing during RT and CCRT. Authors suggest that phenylbutyrate might expedite recovery of OM post RT, and that patients treated with this might also retain the ability to eat more often.


  • Small sample <100
  • Small pilot trial not evaluating for prevention but for treatment.

Nursing Implications:

By decreasing the severity and duration of OM, it can increase the patient’s ability to eat and possibly reduce episodes of N/V. A larger, Phase II trial would be indicated to illustrate benefit. The sample was just over 30.