Management strategies for drug-induced mucositis

According to oncodermatologist Dr Vincent Sibaud (University Institute Cancer Toulouse Oncopole, France), drug-induced mucositis requires an early aggressive treatment [1].

Both chemotherapy and radiotherapy can induce mucositis; although with a different phenotype. Chemotherapy leads to a more diffuse mucositis with poorly limited lesions on a non-keratinised mucosa. Mucositis can be found in the buccal mucosa, on the floor of the mouth, the ventral side of the tongue, and the soft palate. The erythematous or ulcerated lesions are covered with a pseudomembrane. In contrast, radiation therapy leads to a severe mucositis localised within the irradiated field [2]. Mucosa can both be keratinised and/or non-keratinised.

mTOR inhibitors, such as everolimus and temsirolimus, are novel anticancer drugs that induce aphthous-like lesions in up to 50% of treated patients [3]. This is a class effect and the most frequent dose-limiting toxicity of these agents. Mostly, they occur within the first cycle (<8 weeks) after a median onset time of 10 days. Single or multiple, painful, well-circumscribed, round superficial ulcers are found on the non-keratinised mucosa. Targeted therapy, such as angiogenesis inhibitors and anti-EGFR agents, can also lead to mucositis/stomatitis. Usually, lesions are well-demarcated, self-limiting, and aphthous-like, and sometimes occur with dysgeusia. Opportunistic infections, such as candidiasis, are also common.

Immune checkpoint inhibitors lead to specific oral lichenoid reactions [4]. They are either isolated or associated with skin or genital involvement. Lesions look plaque-like, ulcerative, or atrophic/erythematous. Another possible consequence of immune checkpoint inhibitors is sicca syndrome or even autoimmune bullous disorders [5]. Regular oral examinations should be offered to treated patients [6].

“With regard to mucositis management you have to be aggressive,” recommended Dr Sibaud. This approach is also recommended in the ESMO Clinical Practice Guidelines, which state that every patient should receive instructions on daily oral supportive care. They should use a soft toothbrush and nonmedicated oral rinses (e.g. normal saline) [7]. Topical steroids, low-level laser therapy, pain management, and morphine mouthwash are also recommended. The SWISH trial demonstrated the efficacy of a prophylactic use of a dexamethasone-base mouthwash in 85 postmenopausal women receiving everolimus and exemestane for hormone-receptor positive metastatic breast cancer [8]. In this trial, prophylactic use of the mouthwash beginning on day 1 of cycle 1 (10 ml for 2 minutes, and spit; 4 times daily for 8 weeks) was advocated. By 8 weeks, the incidence of ≥ grade 2 stomatitis was 2%, without any grade 3; whereas in a historical cohort 33% had ≥ grade 2 stomatitis [8].

1. 
   
   1. Sibaud V. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
   2. Moslemi D, et al. Radiother Oncol 2016;120:13-20.
   3. Rugo HS, et al. Ann Oncol 2016;27:519-25.
   4. Sibaud V, et al. J Eur Acad Dermatol Venereol 2017;31:e464-469.
   5. Sibaud V. Am J Clin Dermatol 2018;19:345-361.
   6. Vigarios E, et al. Support Care Cancer 2017; 25:1713-39.
   7. Peterson DE, et al. Ann Oncol 2015;26 Suppl 5:v139-51.
   8. Rugo HS, et al. Lancet Oncol 2017;18: 654-62.

 



Posted on 26 August, 201919 March, 2021