Reactive management

Reactive management of stomatitis induced by multikinase inhibitor treatment

General recommendation: Stomatitis can significantly impair quality of life. Comprehensive oral care, aggressive pain management and adequate nutritional support are key considerations.^{1, 2}

Treatment overview

Stomatitis associated with targeted therapies includes a range of subjective and objective symptoms and may differ from the oral mucositis associated with traditional chemotherapy.²

Use of sodium-containing mouthwashes is recommended and the frequency can be increase to hourly if needed.² Symptomatic relief may be obtained using a mouthwash consisting of equal parts of 2% viscous lidocaine, diphenhydramine, and bismuth subsalicylate or aluminium/magnesium hydroxide, or alternative mouthwashes.^3-6 If the patient finds mouthwash use painful, pain medication may be taken first (e.g. viscous lidocaine 2%).^2,6 Aggressive pain relief should be administered, including opioids for persistent severe pain.^{1, 2}

More effective approaches to preventing and treating stomatitis are needed.¹ A Cochrane review of randomised controlled trials identified 10 interventions with some efficacy in either preventing or reducing the severity of oral mucositis during cancer treatment: aloe vera, amifostine, cryotherapy (ice chips), granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymyxin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate.⁷

Patients should be evaluated weekly. With the second or third occurrence of stomatitis intensifying supportive measures is advised. If symptoms worsen despite the intensified measures, drug interruption or discontinuation should be considered.

Table 35: Management of stomatitis associated with multikinase inhibitors, by CTCAE grade grade^2-6

Grade	Description
1	Saline mouthwash
2	Dietary modification (e.g. avoid hot, spicy and acidic food and drinks) Increase the frequency of mouthwash (e.g., every 1–2 h) Use currently available mouthwashes with an antiseptic and analgesic for symptomatic relief If mouthwash is painful, take pain medication first (e.g. viscous lidocaine 2%, coating agents) For moderate pain, consider a topical NSAID (e.g. benzocaine topical 20% mucous membrane spray, gel or liquid, benzocaine topical oral lozenge) Consider initiation of systemic NSAIDs
3	Intensify use of mouthwash to 8–12 rinses per day, or every hour Eat soft foods at room temperature, cut into small pieces; use a straw for drinking liquids Consider corticoid mouthwashes Opioid analgesics if needed. Since oral complaints can complicate administration of drugs by mouth, one should consider other kinds of administration routes, such as transdermal or intranasal routes, e.g. 50 microgram fentanyl nasal spray to relief pain short-term, before dinner
4	Requires tube feeding, analgesic, systemic antibiotic or antifungal treatment or hospitalisation

Products

Viscous lidocaine 2%
Topical NSAID (e.g. benzocaine)
Opioid analgesic

Multikinase inhibitor treatment

Continue with/withhold the selected multikinase inhibitor treatment regimen, as recommended in the current and relevant SPC and according to the patient’s condition.

References

Lacouture ME, et al. MASCC Skin Toxicity Study Group. Support Care Cancer. 2011; 19: 1079-95.
Boers-Doets CB. The TARGET SYSTEM. Approach to assessment, grading, and management of dermatological & mucosal side effects of targeted anticancer therapies. ISBN 978-94-92070-00-5. 2014.
Kollmannsberger C, et al. Oncologist. 2011; 16: 543-53.
De Wit M, et al. Support Care Cancer. 2014; 22: 837-46.
Brose MS, et al. Cancer Treatment Reviews. 2018; 66:64–73.
Krishnamoorthy SK, et al. Therap Adv Gastroenterol. 2015;8:285-97.
Worthington HV, et al. Cochrane Database Syst Rev. 2011 Apr 13;(4): CD00097.