Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy: Beyond the abstract

Oral mucositis (OM) in varying grades pose a significant impediment in the treatment course of the patients of head and neck cancers (HNCs) treated with definitive radiotherapy with or without concurrent chemo-radiotherapy (CTRT). The rates of grade ¾ OM have been found to be as high as 50-80% in the reported literature. This adversely affects the quality of life of patients and also leads to frequent treatment interruptions leading to prolongation of ‘overall treatment time’ which adversely affects the loco-regional control (roughly decrease of 14% per week of prolongation). 

Modifiable treatment related factors include volume of irradiation, sub-site of irradiation (oral cavity versus other sites), total radiation dose (>50 Gray), fractionation strategy employed (conventional versus accelerated) and use of CTRT. Several agents have been tried with a zest to overcome the onslaught of OM. Of these, the only agent with a level I evidence of recommendation [1] is Benzydamine. Benzydamine possess both anti-inflammatory as well as analgesic potential. Currently, the use of this drug is recommended in the prophylaxis of OM in patients receiving moderate doses of radiation (<50 Gray). The results of our present study suggested lower rates of grade ¾ OM (30-35% compared to 50-60%) as well as lower rates of ryle`s tube feeding, need of intravenous fluid supplementation and hospitalization with the use of Benzydamine even in patients treated with higher dose of radiation (>50 Gray). In patients treated with concurrent chemo-radiotherapy, we did observe a non-significant decrease in rates of grade ¾ OM. One of the reasons for this could be higher proportion of oral cavity cancers in the experimental arm of chemo-radiotherapy subset (as compared to controls). We feel that Benzydamine may be effective even in patients treated with CTRT, however this needs to be further tested in a randomized study specially focused on this patient subset.

The other approved intervention for prophylaxis of OM is low level laser therapy (LLLT) and 3. 2 % morphine mouthwash for alleviating pain associated with OM [2]. While the comparative efficacy of Benzydamine to LLLT is yet to be studied, analgesic effects of Benzydamine may in part ameliorate the pain associated with OM. We are planning a further analysis of our reported trial to understand the analgesic potential of Benzydamine and this would be reported soon. 

Our study results have opened up new research questions which could be the hypothesis of future trials. The results of our study should lend support to the design and conduct of large, multicentric, randomized study to further validate the findings of our study. The role of Benzydamine in patients treated with bio-radiotherapy (concurrent cetuximab and nimotuzumab) and with altered radiation fractionation schemes (accelerated and hyper-fractioned) needs to be studied. 

We emphasize that although, Benzydamine reduces the OM rates, other equally important measures (like modification of radiation treatment plan, treatment of concomitant oral infections etc.) should not be ignored in the prophylaxis and treatment of OM associated with head and neck cancer radiotherapy. Novel agents like anti-IL-6 antibodies and antibody specific for tumor necrosis factor (TNF) are also being evaluated for the prevention and treatment of OM. It would be interesting to see how these agents evolve in the future to fit in the management tree of OM.

Written by: Madhup Rastogi1, Ajeet Kumar Gandhi2
Professor1, Assistant Professor2, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow

Conflicts of interest: None


  1. Epstein JB, Silverman S, Paggiarino DA, et al. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer 2001; 92(4):875–885
  2. Lalla Rajesh V, Bowen J, Barasch A, et al. Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) (2014) MASCC/ ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014; 120(10):1453–1461
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