Chitapanarux, I., Tungkasamit, T., Petsuksiri, J., Kannarunimit, D., Katanyoo, K., Chakkabat, C., . . . Traisathit, P. (2018). Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis. Supportive Care in Cancer, 26, 879–886.

To compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemo rt-induced OM in patients with head and neck cancer.

Sixty locally advanced patients with head and neck cancer treated with high-dose RT concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to two weeks after completion of treatment.

• N: 60   
• AGE: 18-70 years
• MALES (%): 24 and 23  
• FEMALES (%): 6 and 7
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Patients with locally advanced head and neck cancer with high-dose radiotherapy and platinum-based chemotherapy 
• OTHER KEY SAMPLE CHARACTERISTICS: Starting similar chemRT regimens; matched

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Chiang Mai UH (CMUH), King Chulalongkom Memorial H (KCMH), Siriraj H (SH) and Udonthani Cancer H (UCH)

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS:  Elder care, palliative care

RCT with two intervention groups

Patients were evaluated by the radiation oncologists at baseline before CCRT, weekly during CCRT, at the end of CCRT, and at four weeks after CCRT. The Oral Mucositis Assessment Scale (OMAS) was used to assess severity of mucositis. Ulceration score was 0 for no lesion, 1 for lesion less than 1 cm², 2 for lesion 1–3 cm², and 3 for lesion more than 3 cm². Erythema score was 0 for no lesion, 1 for mild to moderate erythema, and 3 for severe erythema. Pain score (0–10), all prescribed medications including analgesic, artificial saliva supplement, and anti-infection medications, the need for hospitalization, treatment interruption, and the addition of nutritional support or feeding tube were also recorded. Oral candidiasis assessment was based on the physical examination of pseudomembranous lesions or angular cheilitis in centers except at CMUH center where confirmation by microscopic identification of Candida was used.

Prophylaxis rinsing with benzydamine HCl can be more effective in reducing severity of OM induced by CCRT, when compared to basic care with sodium bicarbonate mouthwash. Median of OMAS scores at weekly assessment during CCRT was lower in benzydamine HCl group compared to control. In both groups, maximum of third quartile of OMAS scores around fifth to seventh week of CCRT. Scores decreased at four weeks after CCRT. Statistically, median for OMAS scores was significantly lower in study group at every week between second and eighth week of CCRT. The corresponding p values for those weeks in chronological order were 0.003, < 0.001, < 0.001, < 0.001, < 0.001, 0.01, and 0.04. Maximum of third quartile of OMAS scores to be around fifth to sixth week in both groups. Maximum OMAS score across whole period of CCRT in benzydamine HCl group was 25, lower than maximum of 37 in sodium bicarbonate group. No significant difference in median of pain scores between two groups during CCRT and at follow-up. Corresponding p values from second to eighth week were 0.88, 0.59, 0.96, 0.73, 0.63, 0.92, and 0.15 and p value at follow-up after CCRT was 0.8. Maximum of third quartile of pain scores at seventh week of CCRT in study group and eighth week in control group. Maximum pain score across period of CCRT was 10 in both groups. Four weeks after CCRT, median of pain score decreased to 2 in both groups. Poor compliance was defined as patients in postoperative CCRT group and in definitive CCRT group who received weekly chemotherapy less than 3 cycles and 4 cycles, respectively. More patients with poor compliance in control group than in study group (i.e., 13 patients versus 10 patients). No differences were found between the two groups. Most patients in both groups need analgesic drugs; 89% in control group and 90% in study group, p value = 1. The most common analgesic drugs used were opioids (syrup morphine/morphine sulfate tablet; MST/morphine sulfate sustain released; kapanol^®), prescribed usage rates were 48% in control group and 33% in study group. For antifungal agents, none in benzydamine HCl group needed them, whereas 19% of patients in sodium bicarbonate group required nystatin oral suspension or clotrimazole tablet. Rate of feeding tube placement was same in both groups during CCRT (i.e., 24 and 22% in the study group and the control group, respectively). Oral retention and compliance for mouthwash products were better in sodium bicarbonate arm than in benzydamine HCl arm. Four patients (6.75%) in study arm could not tolerate full dose of benzydamine HCl due to burning and stinging sensation. For these patients, mouthwash was diluted at 1:1 with water.

Prophylaxis oral rinsing with benzydamine HCl for patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy was superior to sodium bicarbonate mouthwash in terms of alleviating the severity of oral mucositis and encouraging trend for reducing the need of oral antifungal agents use.

• Small sample (< 100)
• Other limitations/explanation: Small study with limitations in descriptive measurement.

Review prophylaxis and acute treatment protocol practices.